Annual Report 2015

ANNUAL REPORT 2015

a G C a T A a t a t c t c t G t C t G a C a a t a t a t a t c g c g t a t a c g c g a a c g c c c g c c g c c a g c c a a t t g a t t g a t c g a t c g g g c C t a a g c a t t t a t a a t g g c g c HIV-1 c a c g a a c g a c C a a t a a t t a a t c g g c c g g c a t a t a t a t c g c g c g c g a g c g a g c g c g t c g t g a t c a t g c c t a t c t a t g c t a g c t a g c t a g c t a g c t a g c c g c t a g c c c a c a a G a C a G C a a c G a C a c a c 5ʼ c a G 5ʼ c c a C IFN-α/β 3ʼ 3ʼ active inactive

The G-YSD motif G-rich Y-form Short DNA Reverse transcription of RNA genome G G G G Y-form DNA Unpaired guanosines G G structure

cGAS STEM: ~20 bp dsDNA Highly structured sequence- ATP, single-stranded DNA independent GTP cGAMP G G Guanosine- G G rich ssDNA G G P IRF3 IRF3 Novel interferon-inducing PAMP or DAMP P Nucleus Cytosol ANNUAL REPORT 2015

Preface p. 9 OVERVIEW Scientific Reports – Research Areas Research Area A: Immune Sensing Receptors and Modulators p. 13 Research Area B: Local Context Sensing p. 21 Research Area C: Metabolic Sensing and Nervous-Immune System Interactions p. 25 Research Area D: Integration of Immune Sensory System Input on the Cellular and Subcellular Level p. 33 Research Area E: Consequences of Immune Sensing for Sterile Inflammationin vivo p. 37 New Developments Technical platform: Transgenic Service p. 41 New Members p. 43 Interviews Dr. Zeinab Abdullah p. 51 Dr. Annkristin Heine p. 53 Dr. Martin Schlee p. 56 Dr. Karin Pelka p. 58 Philipp Schlegel p. 59 Lorenz Omran p. 60 Cluster Coordination Report 7th DAMPs and HMGB1 Meeting p. 67 3rd Cluster Science Days p. 70 Joint ASI-DGfI Workshop Canberra p. 72 Establishment of the DFG-funded IRTG ‘Bo&MeRanG’ with Melbourne p. 73 International Immunology Training Program Bonn (IITB) p. 75 Family Support & Gender Equality p. 84 Public Relations p. 90 Cluster Seminars and Seminars of Cluster Cooperation Partners 2015 p. 92 Cluster Meetings 2015 p. 100

List of Publications p. 103

Prizes & Distinctions p. 153

List of Cluster Members p. 157

Biosketches p. 165

Organigram – Structure of the Cluster p. 203

Participating Institutions p. 205

Cluster Coordination Office (CCO) p. 207

Appendix: Shared Resources p. 209

Imprint p. 211 Preface Preface

The Cluster of Excellence “ImmunoSen- members including senior authors Martin sation”, funded by the German Research Schlee, Gunther Hartmann, Percy Knolle, foundation, DFG, proudly presents you Andreas Zimmer, Wolfgang Kastenmüller its third annual report. The year 2015 and Michael Hölzel. was a great success with many scientific At the core of our Cluster of Excellence and structural achievements, and we are are people and their research activities, deeply grateful for the continued support and these greatly benefit from intellec- of the DFG, the University of Bonn, the tual academic exchange. We proudly German Center of Neurodegenerative announce the recruitment of several Diseases, DZNE, and the Max Planck-as- outstanding scientists as new Cluster sociated Center of Advanced European members over the last year. These are: Studies and Research, caesar. Christoph Wilhelm who was recruited Scientific achievements and the constant as Professor for Immunopathology from striving for scientific excellence are at the the NIH, USA in September 2015, Sven heart of our endeavor. The main section Wehner, who was recruited as Professor of this report is therefore dedicated to for Immunopathophysiology from the Uni- presenting our most important publica- versity of Amsterdam, Andreas Schlitzer, tions from the last year in the research who has been awarded the prestigious fields of innate immune sensing, T cell Emmy-Noether fellowship by the DFG in memory formation, neuro-immunology, November 2015 and joined the LIMES cellular orchestration in the lymphatic Institute from A-Star, Singapore, and system, and cancer immunology. These Annkristin Heine and Zeinab Abdullah, outstanding contributions are fruits of who established two new Cluster Junior the collaborative effort of our Cluster Research groups.

Prof. Waldemar Kolanus (Vice-Speaker) and Prof. Gunther Hartmann (Speaker) (picture by J. Saba UKB)

9 Preface Preface

We have also been able to continue our meetings and lab rotations worldwide. the-art overview of recent achievements the other awardees for their outstanding support of young scientists and expand The Cluster is now fully represented on within this rapidly expanding field of re- scientific discoveries! the international scope of our programs. social media. One great example is the search.Furthermore, the important struc- Last but not least, our Cluster member Cluster member Christian Kurts spear- “ImmunoSensation Blog”, a framework tural impact of our Cluster has become Michael Hoch from LIMES Institute has headed the effort to establish a new DFG in which students and members of the more and more visible through the estab- been appointed as the one-hundred-for- International Research Training Group Cluster regularly exchange information lishment of joint structures with partner in- ty-third Rector of our University. We wish (IRTG) for PhD students, and, in Novem- and expertise. stitutions: for example, Joachim Schultze, him good luck and great success in this ber 2015, the “Bo&MeRanG” program, The international scope of our activities the head of ImmunoGenomics at LIMES prestigious and demanding position! or Bonn & Melbourne Research and has become also more visible through our Institute of the Faculty of Natural Scienc- Graduate training group, was established. contributions to important meetings and es, was co-appointed as a group leader We hope that this short excerpt of our Focusing on “Myeloid Antigen Presenting symposia. The International Symposium at the Genomics Department of the DZNE activities will tempt you to read more Cells and the Induction of Adaptive Im- on DAMPs and HMGB1 was established in September 2015. about our mission in science and in public munity”, the program will promote scien- by the international HMGB1 group of We are also very proud that several mem- outreach. Welcome to ImmunoSensation! tific collaboration between leading immu- scientists with the goal of better under- bers of ImmunoSensation have received nologists from ImmunoSensation and the standing the mechanisms of DAMP and prestigious awards and honors (see page University of Melbourne. In addition to HMGB1 biology and their implications for 153) during the last year. The Gottfried promoting scientific outreach, this pro- disease. This year, we hosted the meeting Wilhelm Leibniz Prize is the most re- Kind regards and best wishes, gram ideally complements our research under Gunther Hartmann’s organization, nowned research prize in Germany and focus. The Cluster contributes broad making it the first time a German site was was awarded to Cluster member Frank Prof. Gunther Hartmann and expertise in immune sensing receptors selected to host this international event. Bradke for his work on neuroregenera- Prof. Waldemar Kolanus and molecular and transcriptional im- The meeting was met with a resounding tion. Congratulations to Frank and all of mune regulation, whereas Melbourne is a international response, and we are proud leading international center in the field of that we could welcome so many interna- immunological defense against infection. tionally renowned experts in innate immu- Moreover, PhD students selected for the nity to Bonn, including Charles Dinarello, program will have the unique opportunity Tak Mak, Marco Bianchi and Michael to obtain instruction and their degree from Lotze who all gave fantastic talks. both universities. The DFG will fund this In addition, the Mini-Symposium “Epi- new joint international graduate college at genetics and Chromatin Structure” took the Universities of Bonn and Melbourne place at the LIMES Institute as a part for 4.5 years starting in April 2016. The of the LIMES Women in Science (WiS) new graduate school will be located at program in March 2015. This program the ImmunoSensation headquarters of is sponsored through the DFG-funded the Bonn Institutes of Immunosciences collaborative research centers SFB 704, and Infection (BI3) and will move into the SFB 645 and TRR 83 at the University new Biomedical Center II (BMZII) currently of Bonn. Among other initiatives, the being constructed on the campus Venus- LIMES-WiS program aims to enhance the berg. visibility of successful female scientists Furthermore, our ImmunoSensation as role models for career development. student training program, the IITB (Inter- LIMES-WiS is also linked with the gender national Immunology Training Program equality program of ImmunoSensation, Bonn), is now fully developed, and its and we are proud to be part of this initia- offers include outstanding training oppor- tive. The Mini-Symposium was organized tunities in a wide spectrum of immunolo- by Cluster members Irmgard Förster and gy-related research areas as well as travel Joachim Schultze and focused on the fellowships for attending international topic of epigenetics to provide a state-of-

10 11 Research Area A: Introduction Immune Sensing Receptors and Innate immune cells have a critical role in can be specific sequences and structural the rapid recognition of and response to features within nucleic acids, covalent Modulators microbial infections and changes in nor- modifications or combination thereof, and mal tissue homeostasis, such as tissue their presence either “disables” or “licens- Prof. U. Benjamin Kaupp, PhD damage, tumor growth or metabolic de- es” recognition by a range of nucleic acid center of advanced european studies and research (caesar) rangements. To perform these vital tasks, sensors. Research in the ImmunoSensa- innate immune cells are equipped with tion Cluster in the last year has uncovered Prof. Eicke Latz, MD PhD a battery of germline-encoded signaling critical details of how RIG-I and cGAS, Institute of Innate Immunity receptors. These molecular sensors can two key cytoplasmic sensors of RNA and Immune Sensing Medical Faculty recognize microbial substances as well DNA, can distinguish between microbial Receptors and as endogenous molecules that appear and host-derived nucleic acids. Martin University of Bonn in the host during disturbances of tissue Schlee and his colleagues were able to Modulators homeostasis. Nucleic acids represent discover that a simple covalent modifica- one class of molecules that can alert the tion to RNA, N12’O-methylation, could immune system to a microbial infection or “tag” RNA as endogenous and prevents that signify damage or stress in cells and RIG-I-mediated immune activation. This tissues. A range of innate immune signal- relatively simple mechanism is a key ing molecules have evolved to recognize checkpoint in the recognition of cytosolic nucleic acids, and these molecules are RNA. In a separate study, Schlee and connected to key signaling pathways colleagues could also identify a novel that can drive potent pro-inflammatory DNA structure which activates cGAS, or anti-viral immune responses. The last which they coin “Y-DNA”. These cGAS decade of research in the immune sens- ligands require critical guanosines and ing of nucleic acids has uncovered many are single-stranded, thus overturning two complex molecular mechanisms which previous paradigms concerning cGAS allow nucleic acid sensing receptors to sensing: (1) that it is inherently sequence distinguish physiologically-occurring nu- independent and (2) that it critically re- cleic acids from those appearing during quires long double-stranded DNA. These infections or cellular stress. One funda- studies provide yet another piece to the mental principle of this process is the use great puzzle of how nucleic acid sensors of specific “molecular tags” on or with the monitor subtle molecular details in nucleic nucleic acids themselves. These “tags” acids.

13 Immune Sensing A conserved histidine in RIG-I controls ral RNA molecules within abundant host immune tolerance to N1-2’O-methylat- RNA in the cytosol is exquisitely chal- Receptors and ed self RNA lenging and usually requires the sensing Modulators of unusual structures or modifications RNA genome-based viruses are some of of viral RNAs. While MDA5 recognizes the most highly pathogenic and emergent (>300nt) long RNA molecules which are currently known (e.g. Influenza, yellow/ double-stranded or build extensive sec- dengue/Lassa fever, Ebola disease vi- ondary structures, RIG-I can be activated rus). The cell-autonomous and systemic by much shorter double-stranded RNA antiviral immune responses against RNA molecules (>19bp) provided that di- or Immune Sensing viruses are initiated by cytosolic RNA triphosphates are present at the 5’end Receptors and sensing innate immune receptors, i.e. ((p)pp-dsRNA), (Hornung et al. 2006; Modulators RIG-I and/or MDA5. These receptors are Pichlmair et al. 2006; Schlee et al. 2009; expressed in most cell types, including Schlee 2013; Goubau et al. 2014). Like somatic cells. The detection of a few vi- most viral RNAs, endogenous mRNA

Figure 2 Graphical Summary of ‘A conserved histidine in RIG-I controls immune tolerance to N1-2’O-methylated self RNA’. Figure 1 His830 in the RIG-I RNA binding domain prevents recognition of endogenous RNA bearing a N1- 2’O-methyl group as a marker of ‘‘self’’ A: Eukaryotes’ mRNA cap (m7GpppNmNm): N1 5’ppp5’ linked to G with N7-methylation. N1/N2 are 2’O-methylated in higher eukaryotes’ mRNA (cap2). B: Chloroquine treated PBMC stimulated with the indi- et al. 2015), we instead used defined syn- (His830) in the C-terminal RNA binding cated synthetic RNA hybridized with complementary RNA. IFN-α production was analyzed 20h after stimula- thetic pppRNA and unexpectedly found domain of RIG-I, which was dispensable tion. C: RIG-I(wt) or RIG-I(H830A) was overexpressed in HEK293blue cells and stimulated with ppp-dsRNA that m7G capped RNA (m7GpppRNA) for RIG-I activation but mediated sterical ligands as in B. IP10 production was analyzed 20h after stimulation. m=2’O-methyl. still profoundly activated RIG-I. This ob- exclusion of N1-methylated RNA. Accord- servation raised the question what feature ingly, we observed that endogenous RNA of mRNA, if not the m7G cap, is actually could stimulate RIG-I if either endogenous bears a triphosphate moiety at its 5’ end, was considered the primary inhibitor of responsible for mRNA immunotolerance cap1 2’O-methylation was inhibited or if but, upon maturation in the nucleus, RIG-I activation via endogenous mRNA. against RIG-I? Higher eukaryotic mRNA His830 was mutated. Strikingly, we also eurkaryotic mRNAs is subjected to 5’ However, this conclusion was based on cap structures also manifest 2‘O-meth- found that RNA viruses exploit this very capping. The cap structure contains the studies which made use of RIG-I ligands yl modifications at N1 (cap1) or N1 and tolerance mechanism to avoid recogni- triphosphorylated 5’ end which is then 5’- produced by enzymatic in vitro transcrip- N2 (cap2) (Banerjee 1980) (Figure 1), tion by RIG-I. The 100% conservation of 5’ linked to a guanosine methylated at N7 tion (IVT). Later, it was discovered that IVT and we discovered that this 2’O-meth- this “licensing” histidine position in RIG-I (m7G) (Figure 1). This m7G cap is pre- also produced unintended immostimu- ylation of the 5’-terminal nucleotide (N1) among vertebrates can even be found requisite for the translation of protein from latory side products which distorted the could completely inhibit RIG-I activation. in sea anemone RIG-I, which highlights most eukaryotic mRNAs whether yeast interpretation of stimulation experiments. Using structure-guided mutations, we the fundamental role of this self-RNA or vertebrates. To date, the m7G cap In the featured study (Schuberth-Wagner could identify a highly conserved histidine tolerance mechanism in evolution. As

14 15 Sequence-specific activation of the IFN response to avoid autoinflammation. such, this is the first study showing the which is expressed in nearly every cell of DNA sensor cGAS by Y-form DNA However, they also hinder the accumu- Immune Sensing biological relevance of endogenous cap our bodies. structures as found in primary HIV-1 lation of cytosolic DNA that arises during Receptors and 2’O-methylation and the corresponding cDNA the replication cycle of this retrovirus enzymes for immune tolerance of self- by Martin Schlee Modulators (Puigdomènech et al. 2013; Yan et al. RNA by RIG-I, an innate immune receptor 2010). Recent research has demonstrat- The type I interferon response is an es- ed that the so-called elite controllers, sential defense mechanism against virus- HIV-1 positive patients who control viral es. Therefore, many viruses have evolved Reference Publication titers without any medical treatment, have mechanisms to evade their detection by reduced TREX-1 and SAMHD1 activity Schuberth-Wagner, C., J. Ludwig, A. RNA bearing 5’-diphosphates.” Nature 514(7522): the pattern recognition receptors that in innate immune cells, enabling the rec- 372-375. K. Bruder, A. M. Herzner, T. Zillinger, M. initiate a type I interferon response. HIV- ognition of HIV-1 by cGAS, the cytosolic Goldeck, T. Schmidt, J. L. Schmid-Burgk, Hornung, V., J. Ellegast, S. Kim, K. Brzozka, A. 1 exploits the human proteins, TREX-1 pattern recognition receptor responsible Jung, H. Kato, H. Poeck, S. Akira, K. K. Conzel- R. Kerber, S. Wolter, J. P. Stumpel, A. and SAMHD1 to avoid recognition. Under for DNA recognition and subsequent mann, M. Schlee, S. Endres and G. Hartmann Immune Sensing Roth, E. Bartok, C. Drosten, C. Coch, V. physiological conditions, these proteins (2006). “5’-Triphosphate RNA is the ligand for type-I-IFN induction (Martin-Gayo et al.; Receptors and Hornung, W. Barchet, B. M. Kummerer, RIG-I.” Science 314(5801): 994-997. act as counterregulators of the Type-I Gao et al. 2013). G. Hartmann and M. Schlee (2015). “A Modulators Pichlmair, A., O. Schulz, C. P. Tan, T. I. Naslund, Conserved Histidine in the RNA Sensor P. Liljestrom, F. Weber and C. Reis e Sousa RIG-I Controls Immune Tolerance to (2006). “RIG-I-mediated antiviral responses to N1-2’O-Methylated Self RNA.” Immuni- single-stranded RNA bearing 5’-phosphates.” Sci- ty 43(1): 41-51. ence 314(5801): 997-1001.

Schlee, M. (2013). “Master sensors of pathogen- a G C a T A a t a t c t c t ic RNA - RIG-I like receptors.” Immunobiology G t C t G a C a a t a t Other Publications 218(11): 1322-1335. a t a t c g c g t a t a c g c g Banerjee, A. K. (1980). “5’-terminal cap structure in a a Schlee, M., A. Roth, V. Hornung, C. A. Hagmann, c g c c c g c c g c c a g c c a eucaryotic messenger ribonucleic acids.” Microbiol a V. Wimmenauer, , C. Coch, M. Janke, t t g a t t g W. Barchet a t c g a t c g g g c C Rev 44(2): 175-205. t a a g c A. Mihailovic, G. Wardle, S. Juranek, H. Kato, T. a t t t a t a a t g g c g c HIV-1 c a c g a Kawai, H. Poeck, K. A. Fitzgerald, O. Takeuchi, S. a c g a c C a a Goubau, D., M. Schlee, S. Deddouche, A. J. Prui- t a a t t a a t Akira, T. Tuschl, E. Latz, J. Ludwig and G. Hart- c g g c c g g c jssers, T. Zillinger, M. Goldeck, C. Schuberth, A. a t a t a t a t c g c g c g c g mann (2009). “Recognition of 5’ triphosphate by a g c g a g c g G. Van der Veen, T. Fujimura, J. Rehwinkel, J. A. c g t c g t g a t c a t g c RIG-I helicase requires short blunt double-stranded c t a t c t a t Iskarpatyoti, W. Barchet, J. Ludwig, T. S. Dermo- g c t a g c t a g c t a g c t a RNA as contained in panhandle of negative-strand g c t a g c c g c t a g c c dy, G. Hartmann and C. Reis e Sousa (2014). “An- c a c a a G a C virus.” Immunity 31(1): 25-34. a G C a tiviral immunity via RIG-I-mediated recognition of a c G a C a c a c 5ʼ c a G 5ʼ c c a C IFN-α/β 3ʼ 3ʼ active inactive

The G-YSD motif G-rich Y-form Short DNA Reverse transcription of RNA genome G G G G Y-form DNA Unpaired guanosines G G structure

Ann Kristin Bruder, Dr. Martin Schlee (picture by Dr. Anna-Maria Herzner) Figure 3 Graphical summary of ‘Sequence-specific activation of the DNA sensor cGAS by Y-form DNA structures as found in primary HIV-1 cDNA’.

16 17 In our research, we examined condi- Our study describes a completely new tions under which SAMHD1 activity is type of cGAS ligand. YSD is a minimal, Immune Sensing suppressed, and we could observe an sequence-specific motif enabling the Receptors and increased accumulation of single-strand- recognition of single-stranded DNA with ed DNA during early HIV-1 infection. In base-paired stretches within their sec- Modulators addition, these conditions also induced ondary structures. Recognition of this a robust, cGAS-dependent type-I-IFN motif enables sensing of early HIV-1 infec- response. We then generated lentiviral tion. Further research will be necessary to particles containing a genetically mod- investigate the importance of this motif in Immune Sensing ified version of the HIV-1 reverse tran- the recognition of other forms of patho- Receptors and scriptase with an impaired production of genic and endogenous DNA. double-stranded (ds)DNA, and this also Modulators lead to enhanced type-I-IFN induction. by Martin Schlee These findings were unexpected, since all previously published data, including Reference Publication crystallization and in-vitro-activation stud- Herzner, A. M., C. A. Hagmann, M. ies of cGAS, had demonstrated that only Goldeck, S. Wolter, K. Kubler, S. Wit- paired, double-stranded DNA with a min- tmann, T. Gramberg, L. Andreeva, K. Dr. Anna-Maria Herzner, Dr. Martin Schlee (picture by Dr. Jonas Doerr) imum of 40 base pairs, but not unpaired, P. Hopfner, C. Mertens, T. Zillinger, T. single-stranded DNA, could activate Jin, T. S. Xiao, E. Bartok, C. Coch, D. cGAS and induce type-I-IFN. While others Ackermann, V. Hornung, J. Ludwig, W. had already shown that double-stranded Barchet, G. Hartmann and M. Schlee stretches of ssDNA could also activate (2015). “Sequence-specific activation type-I-IFN via base-pairing within the of the DNA sensor cGAS by Y-form secondary structure, in HIV ssDNA, the DNA structures as found in prima- predicted secondary structures in base- ry HIV-1 cDNA.” Nat Immunol 16(10): paired stretches still seemed too short 1025-1033. for recognition by cGAS. Surprisingly, we found that the recognition of HIV Other Publications ssDNA was not dependent on its base- paired regions but instead the short, sin- Gao, D., J. Wu, Y. T. Wu, F. Du, C. Aroh, N. Yan, L. Sun, and Z. J. Chen. 2013. “Cyclic GMP-AMP gle-stranded stretches in between them. synthase is an innate immune sensor of HIV and Furthermore, this recognition depended other retroviruses.” In Science, 903-6. on the presence of guanosines within the unpaired stretches. This was unanticipat- Martin-Gayo, E., M. Buzon, Z. Ouyang, T. Hick- ed, since up to then, DNA recognition by man, J. Cronin, D. Pimenova, B. Walker, M. Lichterfeld, and X. Yu. 2015. “Potent Cell-Intrinsic cGAS had been considered sequence-in- Immune Responses in Dendritic Cells Facilitate dependent. However, we observed that HIV-1-Specific T Cell Immunity in HIV-1 Elite Con- this sequence independence was only trollers.” In PLoS Pathog, e1004930. true for base-paired but not for unpaired Puigdomènech, I., N. Casartelli, F. Porrot, and O. DNA. Furthermore, we found that base- Schwartz. 2013. “SAMHD1 restricts HIV-1 cell- paired DNA of any sequence, even as to-cell transmission and limits immune detection short as 12-20 bp, induced a robust in monocyte-derived dendritic cells.” In Journal of type-I-IFN response if it was flanked Virology, 2846-56. with three consecutive guanosines at Yan, N., A. Regalado-Magdos, B. Stiggelbout, M. each possible 3’ or 5’ end. Other flanks, Lee-Kirsch, and J. Lieberman. 2010. “The cytoso- such as cytidines, adenosines or thymi- lic exonuclease TREX1 inhibits the innate immune dines were inactive. We termed this se- response to human immunodeficiency virus type quence-specific cGAS recognition motif 1.” In Nat Immunol. in branched DNA G-ended Y-form short DNA (G-YSD) (Figure 3).

18 19 Research Area B: Introduction Local Context Sensing

In response to an infection with patho- fection, CD8+ T cells usually undergo gens, the immune system mounts a bal- apoptosis. However, some of these acti- anced response to assure control of in- vated killer T cells survive and are termed fection while usually avoiding the onset of memory CD8+ T cells, based on their immunopathology in tissues or lymphoid ability to survive and slowly proliferate in Local Context Prof. Irmgard Förster, PhD organs. Innate immunity provides a first the absence of cognate antigens for long Sensing Immunology and Environment line of protection against infectious micro- periods of time via IL-7 and IL-15-medi- Life and Medical Sciences Institute (LIMES) organisms through a variety of mecha- ated signals. At present, no single marker nisms, including the generation of inflam- exists for memory T cells, but they are University of Bonn mation and the recruitment of phagocytic operationally characterized by the expres- Prof. Percy Knolle, MD immune cells and other cell populations, sion of Bcl2, IL7Rα (CD127) and CD27. some of which can mount immediate Memory T cells are traditionally classified Institute of Molecular Medicine effector functions. Innate immune activa- into two subsets: central memory T cells, University of Bonn tion is also required for the subsequent which reside in lymphoid tissues, and Institute of Molecular Immunology programing of pathogen-specific T cell effector memory T cells in peripheral tis- Technical University Munich responses, where CD8+ T cell driven sues. However, this coarse classification immunity plays a predominant role and, does not fully appreciate the apparent Prof. Waldemar Kolanus, PhD in particular, eventual T cell-dependent plasticity and functional sub-specializa- Molecular Immunology & Cell Biology cytotoxicity. CD8+ T cell differentiation is tion within T memory compartments. The Life and Medical Sciences Institute (LIMES) an integrated process which links multiple following summary of a paper published University of Bonn signals from the local, i.e. organ-specif- by Percy Knolle and colleagues (Böttch- ic, microenvironment and from the cell er et al., Nat Comm. 2015) describes a populations capable of (cross)-presenting new functional marker which allows the antigens derived from infectious micro- discrimination between proliferating and organisms. Co-stimulatory molecules on effector-type memory CD8+ T cells via antigen (cross)-presenting cells (APC) are flow-cytometry, employing the marker essential to the priming of naïve CD8+ CX3CR1. cells. After clearance of the primary in-

Identification of a new marker that stratifies memory T cells with proliferative potential from those with direct effector function

Induction of CD8 T cell memory is critical as liver, lung or skin. Thus, localization for the protection of the organism against of memory CD8 T cells to lymphoid or subsequent encounters with the same peripheral tissues is believed to correlate pathogen. The induction of memory CD8 with proliferative capacity and effector T cells is the result of immune sensing function. which leads to inflammation and the pro- Scientists from the Institute of Experi- gramming of naïve into memory CD8 T mental Immunology, together with the cells. Conventionally, memory T cells have LIMES Institute, the Max Planck Institute been classified according to their anatom- of Biochemistry in Munich and the Clinic ic localization, with central memory T cells for Internal Medicine II at the University residing in lymphoid tissues and effector Hospital Freiburg, have identified a new memory T cells in peripheral tissues, such molecular marker that stratifies memo-

21 ry T cells into those with direct effector sided within secondary lymphoid tissues function or with proliferative potential. such as lymph nodes. Moreover, these Transcriptome and proteome profiling of CX3CR1+ memory CD8 T cells remained memory CD8 T cells identified a differ- in lymph nodes for extensive time peri- entially up-regulated expression of the ods and their slow velocity and scanning fractalkine receptor CX3CR1 on memory of their environment was indicative of CD8 T cells that can exert direct cytotoxic antigen-presenting cells. This indicates effector function and kill their target cells. that these memory CD8 T cell population Such CX3CR1 expression characterized with direct effector function in the lymph memory CD8 T cells with direct cytotoxic nodes may have a role in the rapid initia- effector function in both, mice and hu- tion of CD8 recall responses that is most mans. Conversely, those memory CD8 T efficiently triggered by antigen derived cells that did not express CX3CR1 pro- from dead cells. The correlation of CX- duced high amounts of the cytokine IL-2 3CR1 expression with effector function and showed proliferative potential upon also allowed the quantification of anti- Figure 2 Model for the distinction of memory T Figure 3 Presence of CX3CR1+ CD8+ T cells Prof. Percy Knolle restimulation. Thus, CX3CR1 expression gen-specific memory CD8 T cells with cells upon expression of the marker CX3CR1 in during acute resolved and chronic viral infection. was predicted to correlate with the ana- effector function during viral infection. a group with proliferative potential and with direct HCV-specific CD8+ T cells (top) and CMV-specific + tomic distribution of memory CD8 T cells, In mouse models of acute resolved and effector function. CD8 T cells (bottom). Local Context i.e. CX3CR1+ effector memory T cells chronic LCMV infection, resolved infection were expected in peripheral tissues and demonstrated higher CX3CR1 expression T cells, which could efficiently controlled Reference Publication Sensing CX3CR1- central memory CD8 T cells in on virus-specific memory CD8 T cells cytomegalovirus infection. Furthermore, lymphoid tissues. Surprisingly, CX3CR1+ than chronic infection. Similarly, the num- CX3CR1 expression was a more accurate Jan P. Böttcher, Marc Beyer, Felix Meissner, memory CD8 T cells were detected close ber of CX3CR1+ hepatitis C virus-specific predictor of effector function in memory Zeinab Abdullah, Jil Sander, Bastian Höchst, to the subcapsular sinus in lymph nodes, CD8 T cells was lower in patients with CD8 T cells than expression of the co-in- Sarah Eickhoff, Jan C. Rieckmann, Caroline thus contradicting the accepted notion chronic Hepatitis C compared to the hibitory receptor PD1. The identification Russo, Tanja Bauer, Tobias Flecken, Dominik that only central memory CD8 T cells re- number of Cytomegalovirus-specific CD8 of CX3CR1 as a marker for the functional Giesen, Daniel Engel, Steffen Jung, Dirk H. classification of memory CD8 T cells will Busch, Ulrike Protzer, Robert Thimme, Mat- prove useful in future studies to determine thias Mann, Christian Kurts, Joachim L. the dynamics of immunity during chronic Schultze, Wolfgang Kastenmüller & Percy Figure 1 Model outline for the generation of organ infection or cancer and thus improve T A. Knolle (2015) Functional classification of specific, local T cell memory cell-based immunotherapies. memory CD8+ T cells by CX3CR1 expres- in the liver. sion. Nature Communications Sep 5; 6:8306. by Percy Knolle

Local Context Sensing

Figure 4 CX3CR1 identifies a distinct population of CD8+ memory T cells in lymph nodes. Confocal im- munofluorescence images of popliteal lymph nodes harbouring CX3CR1neg and CX3CR1pos memory OT-I CX3CR1-GFP T cells. 22 23 Research Area C: Introduction Metabolic Sensing and

Nervous-Immune In this research area of the Cluster, we as the receptor mediating the psychoac- address how metabolites are sensed to tive effects of the exogenous cannabinoid Metabolic System Interactions evoke specific immune responses and Δ9-tetrahydrocannabinol (THC) from Sensing and how this affects the nervous system to Cannabis sativa, this sensing of eCBs Nervous- bring about changes in physiology and by CB1 and CB2 is involved in a myriad Immune System Prof. Michael Hoch, PhD behavior. of physiological processes, including the Genetics, Developmental Biology & Molecular Physiology regulation of neuronal activity, inflamma- Interactions In the Hoch lab, the metabolites studied Life and Medical Sciences Institute (LIMES) tion and aging. University of Bonn are ceramides, a special class of lipids, in both Drosophila and mouse. Dro- The Pankratz lab investigates how bacte- Prof. Michael J. Pankratz, PhD sophila has a single ceramide synthase rial infection influences the neural physiol- family member (named Schlank), which ogy and feeding behavior of an organism, Department of Molecular Brain Physiology and Behavior is involved in ceramide synthesis and fat using Drosophila as a model. Drosophila Life and Medical Sciences Institute (LIMES) metabolism. Mammals have six ceramide are an ideal model for identifying novel University of Bonn synthases, of which CerS5 shows the sensors that detect bacteria and their highest homology to Drosophila Schlank. metabolites, and how this message is sig- Prof. Andreas Zimmer, PhD Hoch and his researchers could show naled to the brain to effect an appropriate Institute of Molecular Psychiatry that the specific ceramide generated behavioral response, such as stopping Medical Faculty by CerS5, namely C16:0, promotes food intake. On the one hand, Drosophila University of Bonn diet-induced obesity and insulin resis- brains have a relative “numerical simplic- tance. Since two ceramide synthases ity”. On the other, there are already un- are involved in C16:0 production, CerS5 paralleled genetic tools available for mon- and CerS6, a double knockout was then itoring and manipulating the activity of generated, thus completely abrogating Drosophila neurons. The Pankratz lab has synthesis of C16:0 ceramide. These mu- mapped the motor, neuroendocrine and tants will be used for further studies on sensory cells that mediate chemosensory the influence of C16:0 on fat metabolism, and feeding responses. This has led to physiology and inflammation. the identification of neurons in the brain that detect bitter compounds and make The Zimmer lab has had a long-standing animals move away from a “bitter” food interest in another lipid signaling system: source. Interestingly, some of the neurons the endocannabinoid system. This sys- and neuroendocrine cells may be involved tem includes the cannabinoid receptors, in detecting food-borne bacteria. Work CB1 and CB2, the endogenous canna- is underway to determine the molecular binoid molecules (eCBs), anandamide nature of the receptors in these cells that (AEA) and 2-arachidonoylglycerol (2-AG), sense bacteria and their metabolites. and the enzymes that lead to eCB release. Although CB1 was first discovered

25 Lipid metabolism and innate immune duced weight gain. Moreover, CerS5 KO thus constitutively replenishing their intra- References Metabolic receptor signaling mice are also protected from HFD-in- cellular pools. Sensing and duced obesity and insulin resistance5. Of 1. Voelzmann, A. et al. Nuclear Drosophila We could recently demonstrate important note, CerS5 knockout mice also show In order to investigate the endogenous CerS Schlank regulates lipid homeostasis via Nervous- roles for Ceramide synthases (CerSs) in decreased pro-inflammatory gene expres- production of ceramides and its impact the homeodomain, independent of the lag1p motif. FEBS letters 590, 971–981 (2016). lipid homeostasis1,2,3. However, CerSs sion in adipose tissue. on adipose tissue homeostasis and in- Immune System Interactions is also involved in immunoregulatory cir- flammation, we have generated mice 2. Gosejacob, D. et al. Ceramide Synthase cuits, which we now intend to analyze. Ceramide synthases in immune regu- which are unable to synthesize C16:0-ce- 5 Is Essential to Maintain C16:0-Ceramide Ceramide Synthases (CerS) comprise an lation ramide by crossing CerS5 and CerS6 Pools and Contributes to the Development of enzyme family, which is involved in the deficient mice to delete both genes re- Diet-induced Obesity. The Journal of biologi- production of ceramides, an important Metabolic disorders exhibit strong inflam- sponsible for C16:0-ceramide production. cal chemistry 291, 6989–7003 (2016). class of lipids. CerS enzymes are in the matory characteristics, and, conversely, These mice are born in sub-Mendelian center of sphingolipid de novo synthesis. inflammation is associated with metabolic ratios and suffer from increased lethality 3. Bauer, R. et al. Schlank, a member of the Many pathogenic changes are associated alterations6. Ceramide has been identified shortly after birth, but, CerS5/6 double ceramide synthase family controls growth and with changes in ceramide and/or sphin- as a lipid damage-associated molecular deficient mice that survive the perina- body fat in Drosophila. EMBO J 28, 3706– 3716 (2009). golipid levels. Recently, we could demon- pattern molecule activating the NLRP3 in- tal period continue their development strate that the single Drosophila ceramide flammasome in the context of obesity and without increased lethality. Surprisingly, 4. Merrill, A. H., JR. Sphingolipid and glyco- synthase family member Schlank plays a aging. Previous studies used exogenous these mice show no obvious phenotypes sphingolipid metabolic pathways in the era key role in regulating both ceramide de C6:0-ceramide to investigate ceramide except lowered relative body weight of sphingolipidomics. Chemical reviews 111, 6387–6422 (2011). novo synthesis and body fat regulation. induced inflammasome activation. The and adipose tissue mass even without a All CerS family members share a lag1p endogenous ceramide molecules and its HFD. We plan to reintroduce the ability 5. Turpin, S. M. et al. Obesity-induced motif, which is required for ceramide metabolic synthesis route have not yet to synthesize C16:0-ceramide by bone CerS6-dependent C16:0 ceramide production synthesis and many CerS have a home- been identified. We have analyzed the marrow transfer with hematopoietic stem promotes weight gain and glucose intoler- odomain. In synthesis of ceramide, CerSs sphingolipidome in isolated primary mu- cells from wild type and single (CerS5 or ance. Cell metabolism 20, 678–686 (2014). acylate a sphingoid long-chain base rine bone marrow derived macrophages CerS6) deficient mice and analyze the 6. Zietek, T. & Rath, E. Inflammation Meets (LCB) with a fatty acyl-CoA of distinct in response to TLR (Toll-Like Receptor) consequences on adipose tissue biology Metabolic Disease: Gut Feeling Mediated length to generate (dihydro) ceramide, the activation and subsequent inflammasome under normal and HFD conditions. Us- by GLP-1. Frontiers in immunology 7, 154 backbone of all complex sphingolipids4. activation. We found increased concen- ing this approach, we can discriminate (2016). The number of CerS orthologs in a given trations of ceramide and monohexosylce- between effects of endogenous myeloid Metabolic species varies considerably. Whereas ramide in response to treatment with the ceramide production and sphingolipids mammals express six CerSs, Drosoph- inflammasome activators ATP, nigericin, that are taken up by macrophages from Sensing and ila encodes for only one CerS. The six Imject Alum and palmitate, and also sub- non-myeloid cells. To analyze the acute Nervous- mammalian CerSs show characteristic sequent to prolonged TLR4 activation. and chronic inflammatory response to Immune System substrate specificities towards different These data indicate that sphingolipid ho- HFD in adipose tissue, we plan to devel- Interactions acyl-CoAs. CerS5 and 6 share a common meostasis is disrupted in the context of op a flow cytometry analysis of adipose substrate specificity towards long chain inflammasome activation on a cellular lev- tissue composition, which captures a CoAs (C14:0, C16:0, C18:0) generating el. Now, we plan to analyze the endoge- wide range of cell types from the myeloid C14:0 to C18:0-ceramide. As the murine nous production of ceramides in the con- lineage, T and B cell populations, NK cells CerS5 protein shares the highest se- text of diet-induced obesity and its impact and adipocyte precursor cells. The effect quence homology with Drosophila Sch- on the consequence of adipose tissue of altered sphingolipid synthesis on the lank, we generated and analyzed CerS5 homeostasis and inflammation. All stud- cellular adipose tissue composition has knockout mice. Our group discovered ies performed to date have failed to link not yet been determined. that C16:0-ceramide generated by cer- endogenous de novo ceramide synthesis amide synthase 5 (CerS5) promotes di- in the myeloid lineage with inflammasome by Reinhard Bauer et-induced obesity and insulin resistance2. activation in obesity. However, targeting C16:0-ceramide accumulates especially ceramide synthesis in the myeloid lineage in white adipose tissue after high fat diet may only provide limited information, (HFD) feeding. However, CerS5 knockout since macrophages do not only synthe- mice are protected from HFD-induced size ceramides de novo but can also take C16:0-ceramide accumulation. Deficiency up extracellular sphingolipids from other of CerS5 results in ameliorated HFD-in- sources, such as membrane fragments,

26 27 The endogenous cannabinoid system present in the periphery. The endogenous The ECS is activated under inflammatory Other Publications in neuroinflammation, metabolism and ligands of CB1 and CB2, the so-called conditions, resulting in an increased pro- Metabolic aging endocannabinoids (eCBs), are N-arachi- duction of eCBs and changes in the ex- 1. Maccarrone M, Bab I, Bíró T, Cabral GA, Sensing and donoylethanolamine (AEA) and 2-arachi- pression of cannabinoid receptors. Thus, Dey SK, Di Marzo V, et al. (2015): Endocanna- The endogenous cannabinoid system donoylglycerol (2-AG). Both are metabo- expression of CB2 receptors is often low binoid signaling at the periphery: 50 years af- Nervous- ter THC. Trends Pharmacol Sci. 36: 277–296. (ECS) is a lipid signaling system that was lites of membrane phospholipids but are in healthy tissues, including the central Immune System originally discovered through studies on produced by independent biochemical nervous system, but strongly induced 2. Nozaki C, Markert A, Zimmer A (2015): In- Interactions the chemistry of Cannabis sativa extracts pathways. 2-AG (and possibly also AEA) under pathological conditions such as hibition of FAAH reduces nitroglycerin-induced and its major psychoactive constituent is a retrograde synaptic messenger that neuropathic pain or in neurodegenerative migraine-like pain and trigeminal neuronal Δ9-tetrahydrocannabinol (THC). This can prevent the development of exces- disorders. This activation is important to hyperactivity in mice. European neuropsycho- constituent activates G-protein-coupled sive neuronal activity, a regulatory action counterbalance the inflammatory pro- pharmacology : the journal of the European receptors, known as type 1 or type 2 of major importance. The ESC is not only cesses and necessary to restore tissue College of Neuropsychopharmacology. doi: cannabinoid receptors (CB1, CB2). CB1 important for brain physiology but also in homeostasis (1). A reduced endocanna- 10.1016/j.euroneuro.2015.04.001. is prominently expressed in the central many other tissues. It is thought to be a binoid tone can thus aggravate neuroin- nervous system, whereas CB2 is mainly key regulator of tissue homeostasis. flammation and result in the development 3. Schmöle A-C, Lundt R, Ternes S, Albayram O, Ulas T, Schultze JL, et al. (2015): Canna- of neuropsychiatric symptoms (2-4). The binoid receptor 2 deficiency results in reduced CB2 receptor in particular seems to be at neuroinflammation in an Alzheimer’s disease the nexus of inflammation and neuronal mouse model. Neurobiology of aging. 36: a Cellular level activity (5). 710–719. The activity of the ECS is not constant CB1 Metabolic �Akt throughout life. It peaks during adoles- 4. Jenniches I, Ternes S, Albayram O, Otte cence and slowly declines during aging DM, Bach K, Bindila L, et al. (2015): Anxiety, Sensing and �mTOR Nucleus Stress, and Fear Response in Mice with Re- Nervous- Mitochondrion (6). It has been suggested that the decreased endocannabinoid tone in older duced Endocannabinoid Levels. Biol Psychia- m-CB1 ? Immune System �p70S6K individuals contributes to some symp- try. doi: 10.1016/j.biopsych.2015.03.033. Lysosome Autophagosome Interactions • Respiration toms of the aging process (Di Marzo et • Mitochondrial cAMP 5. Stempel AV, Stumpf A, Zhang H-Y, I-CB1 • � Autophagy • Mitochondrial PKA • � Autophagic al., 2015; Figure 1). Indeed, animals with Özdoğan T, Pannasch U, Theis A-K, et al. CB1 deletion disrupted cannabinoid receptors show (2016): Cannabinoid Type 2 Receptors Medi- • Ca 2+ release an accelerated appearance of indicators • � Permeability ate a Cell Type-Specific Plasticity in the Hip- • Release of cathepsin D of brain aging such as neuronal loss and pocampus. Neuron. 90: 795–809. • Cathepsin D in mice with CB1 deletion chronic neuroinflammation, bone loss and atrophy of the subdermal fat layer 6. Piyanova A, Lomazzo E, Bindila L, Lerner b Tissue level c Organism level (7-9). Polymorphisms in the CB2 recep- R, Albayram O, Ruhl T, et al. (2015): Age-related changes in the endocannabinoid system TRPs tor in humans also result in an enhanced �Microglia • in the mouse hippocampus. Mech Ageing Microglia • Neurodegeneration age-related bone loss and an increased activation �Astrocyte Astrocyte Dev. 150: 55–64. DAG activation vulnerability to develop psychiatric disor- Hypothalamic DAGL eCBs activity ders. We are currently investigating the 7. Bilkei-Gorzo A, Racz I, Valverde O, Otto M, precise cellular and molecular mecha- DAGL Michel K, Sastre M, et al. (2005): Early age-re- PIC CB1 DAG nisms involved in the regulation of the en- lated cognitive impairment in mice lacking �Brain mGluR Fat cells docannabinoid tone and are exploring the cannabinoid CB1 receptors. Proc Natl Acad Metabolic therapeutic potential of ECS modulators Sci USA. 102: 15670–15675. processes Presynaptic Postsynaptic for age-related symptoms. 8. Albayram O, Alferink J, Pitsch J, Piyanova Metabolic by Andreas Zimmer A, Neitzert K, Poppensieker K, et al. (2011): NMDA regulation Role of CB1 cannabinoid receptors on GAB- �Osteoporosis Aergic neurons in brain aging. Proc Natl Acad Reference Publication Glu Sci USA. 108: 11256–11261. �DSI in mice with CB1 deletion Di Marzo V, Stella N, Zimmer A (2015): 9. Bilkei-Gorzó A, Drews E, Albayram O, Pi- Endocannabinoid signalling and the Figure 1 Age-related changes at different system levels and their regulation by endocannabinoid signal- yanova A, Gaffal E, Tueting T, et al. (2012): ling. Ageing is accompanied by changes in cellular processes, impairments in the integration of cellular deteriorating brain. Nat Rev Neurosci. Early onset of aging-like changes is restricted activities, and deficits in physiological functions. From Di Marzo, Stella, Zimmer Nature Reviews Neuro- 16: 30–42. to cognitive abilities and skin structure in Cnr1 science (2015). mice. Neurobiology of aging. 33: 200.e11–22.

28 29 ideal model system to study the molec- gether, our study will facilitate the identifi- ular mechanisms underlying brain-gut- cation of upstream cellular elements and immune interactions. In previous work, CNS modulators that effect feeding activ- we have investigated motor programs in ity. Current work focuses on interneurons Metabolic the Drosophila brain for the suppression expressing the neuropeptide hugin which, of food intake and induction of avoidance when activated, inhibit feeding and po- Sensing and (Schoofs et al, 2014; Please see publica- tentially process bitter taste information Nervous- tion summary in ImmunoSensation Annu- within the Drosophila larval brain. Further Immune System al Report 2014.). In a recent publication studies are currently addressing whether Interactions (Hückesfeld et al, 2015), we were able to gustatory receptors are able to mediate contribute fundamental information nec- the taste of bacteria in order to change essary to further studies on this subject feeding behavior. by mapping the motor components that underlie feeding behavior. Using a photo- Reference Publication activatable GFP system, we characterized the motor neurons of the Drosophila larval Hückesfeld, S., Schoofs A, Schlegel P, feeding motor system, which allowed us Miroschnikow A, Pankratz M. (2015) to then make use of a genetically-encod- Localization of motor neurons and ed calcium indicator GCaMP3 to monitor central pattern generators for motor the activity of the identified motor neurons patterns underlying feeding behavior and compare them to electrophysiological in Drosophila larvae. PLoS One 10(8): recordings. In addition, we were able to e0135011. characterize the ipsi- and contralateral innervation patterns of the cibarial dilator Other Publications Figure 2 Identification of feeding motor neurons and taste circuits mediating bitter aversion musculature (CDM) by single Antennal To understand the regulation of feeding behavior, motor neurons responsible for the control of food intake in Dro- Nerve (AN) motor neurons. Using a tem- Schoofs A, Hückesfeld S, Schlegel P, Miro- sophila were identified (the AN motor neurons). In parallel, it could be shown that a cluster of eight interneurons in perature-sensitive inhibitor in glutama- schnikow A, Peters M, Zeymer M, Spieß R, Chiang AS, Pankratz MJ. (2014) Selection of the brain (hugin-PC neurons) receive sensory input from bitter gustatory receptor neurons (gustatory receptor 66a). tergic neurons, shibireTS, we could then These interneurons express the neuropeptide hugin (homolog of mammalian neuromedin U) and their activity leads to motor programs for suppressing food intake a decrease of feeding motor patterns (adapted and modified from Hückesfeldet al., 2015). Bitter taste is commonly block synaptic transmission from the AN and inducing locomotion in the Drosophila associated with toxic or even pathogenic substances like bacteria, and current research is exploring whether bitter to CDM, allowing us to modulate and brain. PLoS Biol. 2014. class of gustatory receptors can also sense bacteria/bacterial metabolites to alter feeding behavior. inhibit feeding behavior. Moreover, we determined that the central pattern gen- Medzhitov R, Schneider D, Soares M (2012). erator for larval feeding in Drosophila is Disease tolerance as a defense strategy. Sci- Taste circuits mediating bitter and sibility these taste receptors in the gut located in the subesophageal zone. Alto- ence 335, 936-941. food aversion behavior may also influence the brain to undergo aversion behavior in response to bacte- In addition to direct anti-microbial mech- rial infection. Moreover, it also poses the anisms, an organism uses many other question whether similar regions in the strategies to detect and defend itself brain might be acted upon by perception against harmful substances, such as of bitter taste from the internal and exter- Metabolic avoidance (Medzhitov et al, 2012). Bitter nal environments. Sensing and taste is normally associated with detec- Our lab has been addressing how tion of harmful substances and evokes bacteria influence behavior using Dro- Nervous- an avoidance behavioral response, such sophila melanogaster. The brain, and Immune System as moving away from the source. Such its interaction with the periphery are Interactions reactions are mediated by specific sets of complex: there are 10,000 neurons in fly taste receptors that usually reside in the larval brain, but this is still far few fewer mouth region. However, recent finding than the 70,000,000 in the mouse and indicate that bitter taste receptors are 85,000,000,000 in humans. In addition, found internally as well, such as in the there are powerful tools available to mon- gut, and may be involved in detecting itor and modulate Drosophila neuronal harmful bacteria, thus raising the pos- activity. Thus, Drosophila provides an

Prof. Michael Pankratz, Sebastian Hückesfeld 30 31 Research Area D: Introduction Integration of Immune

Sensory System Input Over the last two years, important ad- reconsider this dichotomous approach. Integration of vances have been made in our under- In their study, Joachim L. Schultze and Immune Sensory on the Cellular and standing of the role of signal integration his colleagues propose a multidimension- in the myeloid compartment. Together al, stimulus-oriented model of macro- System Input on Subcellular Level with colleagues from Singapore, Memphis phage activation and phenotypic classifi- the Cellular and and New York, Joachim L. Schultze has cation. One of the great benefits of such Subcellular Level outlined a new multidimensional concept a system is that it can take into consider- of macrophage ontogeny, activation and ation both the ontogeny and spatiotem- function. poral microenvironment of individual cells. Prof. Christian Kurts, MD However, deconvoluting complicated cell Institute of Experimental Immunology New insights into the multidimensional populations will also require expert use Medical Faculty concept of macrophage ontogeny, ac- of cutting-edge technologies. Here, the University of Bonn tivation and function. authors provide a “roadmap” for the un- biased, high-resolution analysis of mac- Prof. Joachim L. Schultze, MD Ginhoux F*, Schultze JL*, Murray PJ*, rophage populations from specific tissues Genomics & Immunoregulation Ochando J*, Biswas SK*. Nat Immunol. in homeostasis and during disease, in- Life and Medical Sciences Institute (LIMES) 2016 Jan;17(1):34-40. published on- cluding a variety of single-cell sequencing University of Bonn line 17 December 2015, doi: 10.1038/ techniques and deep immunophenotypic ni.3324. * all authors contributed equally assessment with cytometry by time-of- flight mass spectrometry (CyTOF). Macrophage biology has been the subject Given the preeminent role macrophages of intensive research for many years, yet play in tissue homeostasis, disease and we are only beginning to appreciate the repair, these cells are undoubtedly ex- intricacies of their development and func- ceptionally attractive targets for immu- tion. Previous systematic classifications nomodulatory therapies. Thus, better of macrophages were based on a polar understanding their heterogeneity will al- dichotomy between inflammatory (M1) low research to bypass the “roadblocks” and anti-inflammatory (M2) states. How- posed by the oversimplifications of the ever, new advances, such as transcrip- polar activation model, to the benefit of tome-based networks and epigenetic both basic science and clinical therapeu- analysis, have compelled researchers to tic strategies.

33 The orchestration of cellular interactions during the activation of cytotoxic lymphocytes. provide help, remained unclear. Impor-

Integration of tantly and in contrast to B cells, CD8 T In order to mount a potent adaptive im- cells cannot directly interact with CD4 T Immune Sensory mune response, immune cells need to cells but instead do this using DCs as a System Input on interact and communicate, an essential proxy. In our recent work, we examined prerequisite for lymphocyte activation, the Cellular and which subset of DC serves as the critical proliferation and differentiation. In the Subcellular Level proxy for CD4 T cells to help CD8 T cells. context of humoral responses, CD4 T Surprisingly, we found that, in context of cells are first activated by dendritic cells viral infections, CD4 and CD8 T cells are (DC) in secondary lymphoid organs lead- initially activated separately by different ing to an altered chemokine receptor DC. Once both lymphocyte subsets have expression pattern and subsequent mi- become activated, they seek out XCR1 gration to the T-cell/ B-cell border. Here, DC, which we have identified as the crit- CD4 T cells interact with and provide help ical platform that brings CD4 and CD8 T to antigen-presenting B cells, thereby cells together. initiating a complex order of events that is Altogether, our study has elucidated the called the germinal center reaction (Victo- spatitemporal dynamics of CD4 help to Integration of ra et al. 2012). cytotoxic CD8 T cells and identified XCR1 It is well established that CD4 T cells do Immune Sensory DC as non-redundant DC subset that not only help B cells to produce neu- System Input on serves as a communication platform to tralizing antibodies but also support the mediate helper signals to CD8 T cells. the Cellular and formation a functional memory T cell Our current findings provide a framework compartment from cytotoxic CD8 T cells Subcellular Level for the design of novel vaccines that (Castellino et al. 2006). Until recently, the aim to elicit a potent cellular immune re- spatiotemporal dynamics of those inter- sponse as required for anti-tumor therapy actions, i.e. when and where CD4 T cells and a variety of other applications.

by Wolfgang Kastenmüller

This oil on canvas image shows moth (CD4 and CD8) being attracted to light (XCR1) that is operated by a viral particle. It illustrates our central finding that XCR1 DC act as a critical platform that brings CD4 and CD8 T cells together to allow for the deliv- ery of help. This “menage à trois” is important for optimal cytotoxic T cell responses in the context of viral infections. Image created by Dr. Marianne Janas.

Reference Publication Other Publications

Eickhoff S, Brewitz A, Gerner MY, Klaus- Victora GD, Nussenzweig MC. Germinal cen- chen F, Komander K, Hemmi H, Garbi N, ters (2012). Annu Rev Immunol.;30:429-57. Kaisho T, Germain RN, Kastenmuller W. Castellino, F., and Germain, R.N. (2006). Co- 2015. Robust Anti-viral Immunity Re- operation between CD4+ and CD8+ T cells: quires Multiple Distinct T Cell-Dendrit- when, where, and how. Annu. Rev. Immunol. ic Cell Interactions. Cell 162: 1322-37. 24, 519–540.

f.l.t.r.: Prof. Wolfgang Kastenmüller, Anna Brewitz, Karl Komander and Sarah Eickhoff (picture by K. Kastenmüller)

34 35 Research Area E: Introduction Consequences of Immune Sensing for Inflammation during infection is essential phenotype” with its reduction leading to Consequences to pathogen clearance and tissue repair. dedifferentiation. Thus, this new insight Sterile Inflammation However, immune sensors can also in- into MITF signaling provides new ap- of Immune duce inflammation in response to “sterile proaches to the targeted immunotherapy Sensing for in vivo conditions”, such as tissue damage, a of melanoma. Sterile Inflam- process with the inherent potential of in- Another important disease in the context mation in vivo ducing chronic inflammatory states. Such of sterile inflammation is Alzheimer’s dis- chronic sterile inflammation drives the ease (AD), and the role of inflammation Dr. Annett Halle, MD pathogenesis of many human diseases, in AD has been the focus of the research center of advanced european studies and research (caesar) including atherosclerosis, and Alzheimer’s of Cluster members Michael Heneka, disease. In addition, it participates in the Annett Halle and Eicke Latz for some etiology of many cancers by promot- time. In the Lancet Neurology review Prof. Gunther Hartmann, MD ing neoangiogenesis and tumor stroma “Neuroinflammation in Alzheimer’s dis- Institute of Clinical Chemistry and Clinical Pharmacology development. Within research area E, ease”, these researchers as well as other Medical Faculty we aim to unravel the underlying mech- luminaries in the fields of inflammation University of Bonn anisms of sterile inflammation in order and neurology, clearly state and support to better understand these illnesses and that neuroinflammation contributes to AD Prof. Michael Heneka, MD develop novel therapeutic strategies. In progression just as much as Aβ plaques. Clinical Neuroscieces Unit their previous work, Cluster members In this review, they provide insight into the Medical Faculty Michael Hölzel and Thomas Tüting could cellular mechanisms of AD, the mediators University of Bonn link pro-inflammatory signals, particular- and modulators of neuroinflammation, ly TNF-α, to relapse in melanoma after and new approaches to analyse, char- Prof. Veit Hornung, MD adopted T cell therapy (Landsberg et acterise and finally treat AD with the help Institute of Molecular Medicine al., 2012). Immune-cell derived TNF-α of anti-inflammatory drugs. In “Innate im- Medical Faculty induced reversible melanoma dedifferen- munity in Alzheimer’s disease”, a review University of Bonn tiation and “phenotype switching”, allow- published in Nature Immunology, Michael ing cells to stop expressing melanocytic Heneka, Eicke Latz, and Douglas Golen- Gene Center Munich antigens, escape recognition by cytotoxic bock, a member of the Scientific Advisory T cells and promoting relapse. In their re- Board of the Cluster, also shed light on cent work (Riesenberg et al., 2015), they the role of innate immune sensing in AD. have further elucidated this phenomenon Here, they detail the newest advances in by characterizing the molecular pathways our understanding of the pathogenesis of through which TNF-α-induced dedifferen- Alzheimer’s disease and the causal role of tiation takes effect. Their study, which is inflammatory responses. summarized in this chapter (see page 38), Altogether, Cluster research groups have describes a novel feed-forward mecha- continued to contribute to our under- nism by which TNF-α induces the activity standing of chronic sterile inflammation of the c-Jun, which, in turn, suppresses in human disease, and their research the melanocytic lineage transcription has contributed to the identification of factor microphthalmia-associated tran- putative therapeutic targets for common scription factor (MITF). MITF is the central inflammatory diseases and cancer. transcription factor of the “melanocyte

Heneka M, [...] Latz E, Halle A, [...], Kummer P Heneka M, Golenbock D & Latz E Neuroinflammation in Alzheimer’s Disease Innate Immunity in Alzheimer’s Disease Lancet Neurology (2015) Nature Immunology (2015)

37 Consequences Tumors are complex entities that are and particularly within the first funding and functional genomics approaches Reference Publication of Immune characterized by aberrant tissue ar- period of our Cluster of Excellence Immu- and found that the melanocytic lineage chitectures. In addition to tumor cells, noSensation, we have discovered pivotal transcription factor MITF (microphthal- 4. Riesenberg S, Groetchen A, Sid- Sensing for non-malignant cell types such as stro- roles for reciprocal interactions between mia-associated transcription factor) acts daway R, Bald T, Reinhardt J, Smorra D, Sterile Inflam- ma, endothelial and in particular immune melanoma and immune cells in the tumor as potent repressor of inflammatory Kohlmeyer J, Renn M, Phung B, Aymans mation in vivo cells critically contribute to tumorigene- microenvironment1-4. Recruited immune signaling in melanoma cells4. As MITF is P, Schmidt T, Hornung V, Davidson I, sis. Currently, our main research focus cells evoke inflammatory responses in the key regulator of the differentiation/ Goding CR, Jönsson G, Landsberg J, is malignant melanoma, an aggressive the tumor tissue and thereby critically pigmentation gene program, our finding Tüting T, Hölzel M MITF and c-Jun type of skin cancer that originates from change the biological behavior of the mel- clearly links dedifferentiation of melanoma antagonism interconnects melanoma pigment-producing melanocytes. New anoma cells, a phenomenon also known cells to the acquisition of an inflammatory dedifferentiation with pro-inflammatory types of therapy including the use of on- as phenotypic plasticity5. Specifically, cell state with important implications for cytokine responsiveness and myeloid cogenic signaling inhibitors and immuno- inflammatory signals such as the cytokine the tumor and immune cell cross-talk in cell recruitment. Nat. Commun. 6, 8755 therapeutic approaches have remarkably TNF-α are capable of rapidly inducing the microenvironment6. Specifically, we (2015). improved the prognosis of patients with the dedifferentiation of melanoma cells, identified a reciprocal antagonism be- metastatic melanoma. In recent years i.e. downregulation of the pigmentation tween MITF and c-Jun, a stress-inducible Other Publications transcription factor and component of the so-called AP-1 complex that promotes 1. Landsberg, J. et al. Melanomas resist T-cell cytokine gene expression (Figure 1). We therapy through inflammation-induced revers- showed that pro-inflammatory cytokines ible dedifferentiation. Nature 490, 412–416 like TNF-α instigate gradual suppres- (2012). sion of MITF expression through c-Jun. However, MITF, itself, binds to the c-Jun 2. Bald, T. et al. Immune cell-poor melanomas Consequences regulatory genomic region, acting as a benefit from PD-1 blockade after targeted of Immune transcriptional repressor, and, therefore, type I IFN activation. Cancer Discov. 4, 674– Sensing for its reduction increases c-Jun expression, 687 (2014). which in turn amplifies cytokine expres- Sterile Inflam- sion. This feed-forward mechanism turns 3. Bald, T. et al. Ultraviolet-radiation-induced mation in vivo poor, peak-like transcriptional responses inflammation promotes angiotropism and me- to TNF-α into progressive and persistent tastasis in melanoma. Nature 507, 109–113 cytokine and chemokine induction by (2014). melanoma cells. This explains why in- Figure 1 Summary of our low high findings showing how the flammatory MITF /c-Jun syngeneic 5. Hölzel, M., Bovier, A. & Tüting, T. Plasticity antagonism between MITF mouse melanomas strongly recruit my- of tumour and immune cells: a source of hetero- and c-Jun controls cytokine eloid immune cells into the tumor micro- geneity and a cause for therapy resistance? Nat. responsiveness of melanoma environment, a phenotype that could be Rev. Cancer 13, 365–376 (2013). cells and thereby the immune recapitulated in matched human patient cell composition of the tumor microenvironment. Figure from specimens. Our findings suggest that 6. Hölzel, M. & Tüting, T. Inflammation-In- Hölzel et al., Trends in Immu- myeloid cell-directed therapies may be duced Plasticity in Melanoma Therapy and Me- nology. useful for MITFlow/c-Junhigh melanomas to tastasis. Trends Immunol. 37, 364–374 (2016). counteract their tumor growth-promoting and immunosuppressive functions. In summary, understanding the reciprocal Prof. Michael Hölzel interactions between melanoma and im- gene program and acquisition of migra- signals are coordinated within melanoma mune cells is important for the rational tory neural crest progenitors properties. cells to orchestrate phenotype switching design of new clinical studies that evalu- In our research, we have demonstrated in a pro-inflammatory microenvironment. ate immunotherapeutic approaches, as how this inflammation-induced plasticity It has also remained unexplained whether different immune cell compositions of the of melanoma cells can cause resistance or to what degree different melanoma cell tumor microenvironment will require differ- to T cell immunotherapy1 and promote states instruct the immune cell composi- ent combinatorial strategies. metastatic progression in response to tion of the tumor microenvironment. UV irradiation3 of the skin. However, it To address these important questions, by Michael Hölzel has remained unclear how inflammatory we performed a series of transcriptomic

38 39 New Developments The Transgenic Service Core Facility Genetically modified mice in biomedical research

Transgenic mouse models are a crucial system consists of the Cas9 nuclease or Technical Platform: Prof. Andreas Zimmer tool for the understanding of gene and nickase and a single guide RNA (sgRNA). Transgenic Service Institute of Molecular Psychiatry protein functions. At the Transgenic Ser- sgRNA is approximately 20 nucleotides in The Transgenic University of Bonn vice Core Facility (TGS), we have expert length and escorts the Cas9 to the target Service Core scientific and technical knowledge in the sequence, where it generates double or Facility generation of genetically modified mice single-stranded DNA breaks. When these Dr. David-Marian Otte using a variety of different techniques. The breaks are repaired by the cell, muta- Haus für experimentelle Therapie (HET) core facility produces transgenic mice for tions can occur in a process known as University of Bonn a variety of applications. Thus, mice can non-homologous end joining. To generate be designed to overexpress proteins, to transgenic mice with CRISPR/Cas9, the New Members Prof. Matthias Geyer, PhD express tagged proteins or to express sgRNA and Cas9 (RNA or protein) are Prof. Christoph Wilhelm, PhD genes in a tissue or time-dependent injected into a zygote. Moreover, co-injec- Dr. Zeinab Abdullah, PhD manner using specific Cre mouse lines. tion of a DNA fragment with homology to Dr. Annkristin Heine, MD Furthermore, we are currently establishing the sequences flanking the double-strand PD Dr. Marc Beyer, MD the generation of knockout or knockin break can produce mutant alleles with Dr. Martin Schlee, PhD mice using the CRISPR/Cas9-mediated inserts such as loxP sites. An illustration Dr. Andreas Schlitzer, PhD gene editing approach. CRISPR/Cas9 is of the experimental procedure for the a new and very powerful tool for editing CRISPR/Cas9-mediated gene editing is Prof. Sven Wehner, PhD genomes which is based on the immune shown in Figure 1. system of bacteria and archaea. The

Figure 1 Schematic representation of gene editing options using the CRISPR/Cas9 system. Adapted from Yang et al., 2014 Nature Protocols.

41 Ancillary services cages (IVCs), and their well-being is mon- itored on a daily basis. Adjacent to the New Developments - Member The Transgenic Service Core Facility holding cages, we run the microinjection offers support, advice and counseling unit, which is equipped with specialized for non-specialists in recombinant tech- microscopes with micromanipulators to niques, mouse breeding, gene-targeting inject nucleic acids and proteins. Here, experiments and the regulatory approval we also perform the embryo cryopreser- of certain animal experiments. Additional- vation. Within the laboratory area of the We are proud to have been able to recruit and their research, please see below.) ly, we archive genetically modified mice as facility, we run a molecular biology labora- eight outstanding scientists as new Clus- We would also like to congratulate Veit embryos frozen in liquid nitrogen and also tory with state-of-the-art methods for the ter members over the last year: Christoph Hornung and Thomas Tüting for their have the capability of rederiving mouse generation of plasmids and RNA. Wilhelm and Matthias Geyer, who were appointments to the faculty of the Gene strains from frozen stocks (sperm or recruited for Cluster professorships in Center Munich and the University Hospi- 2-cell stages). On demand, we can also Reference 2015, Annkristin Heine and Zeinab Abdul- tal Magdeburg, respectively. Although no import mouse strains from other institutes lah, who established two new Cluster ju- longer in Bonn, they will remain members and companies into our animal facility via Generating genetically modified mice nior research groups, Marc Beyer, Martin of the Cluster for the remaining funding embryo transfer. using CRISPR/Cas-mediated genome Schlee, Andreas Schlitzer and Sven Weh- period. We wish them all the best and engineering. Yang H, Wang H, Jaenisch ner, who are new Cluster members. (For great success in their new positions. Equipment and mice R. Nat Protoc. 2014 Aug;9(8):1956-68. more information on all of these scientists doi: 10.1038/nprot.2014.134. Epub 2014 The TGS is located in a modern, state- Jul 24. of-the-art animal facility at the clinical campus. We keep our genetically modified mice in a separate holding area with limited access to avoid contaminations. All mice are kept in internally ventilated

Veit Hornung Immune Biochemistry, LMU Thomas Tüting Dermatology, University Hospital Munich Magdeburg by Johann Saba, UKB-Ukom by Johann Saba, UKB-Ukom The Transgenic Service Core Facility Matthias Geyer Cluster chair for Structural Immunology

The immune system is permanently de- lecular assembly, called the inflam- fending the human body against a wide masome. The Geyer lab is using a broad range of different pathogens. A common variety of molecular, biochemical and response to these harmful stimuli is in- structural techniques to study the effects flammation. The cytosolic receptor pro- of activation and nucleotide binding in tein NLRP3 is one member of the family NLRs. The correlation of structure-func- of Nod-like receptors (NLRs) that sense tion relationships in NLRP3 provides inflammation. NLRP3 recognises patho- insights into the the molecular assembly gen-associated and danger-associated of the inflammasome and yields key sites molecular patterns in immune cells. These for the regulation and targeted inhibition molecular patterns lead to activation of of this immune receptor. In addition, the Prof. Andreas Zimmer Dr. David-Marian Otte NLRP3 and the formation of a high-mo- lab studies the regulation of transcription by Thomas Mauersberg

42 43 kinases Cdk7 to Cdk13 and analyses immunity with increased gastro-intestinal responses and repair mechanisms could how in eukaryotic cells the transition pathology but also enhanced immunity to be beneficial in the context of chronic from transcription initiation to productive helminth infections, despite a previous- infections with tissue dwelling parasites. elongation is mediated. The malfunction ly reported dysfunction in T and B cells Both parameters, malnutrition and helmith of transcriptional elongation leads to mul- during vitamin A deficiency. The important infections, are largely absent in the west- tiple diseases as many forms of cancer, implication of this discovery is that, unlike ernized world, which is instead plagued New leukaemia, HIV infection and myocardial the adaptive immune response, ILC-me- by a multitude of inflammatory diseases. Developments hypertrophy. Matthias Geyer is using a diated barrier immunity is able to adapt to Hence investigating the protective func- - broad range of biochemical methods to malnutrition by switching to an ILC2-me- tion of ILC in the context of malnutrition Member determine protein-protein interactions as diated response and maintaining the gut could lead to new opportunities for ma- well as interactions to lipids, nucleic acids barrier. Such dynamic regulation by di- nipulating their function for therapeutic Prof. Matthias Geyer by Johann Saba, UKB-Ukom and small molecular ligands. The labora- etary components away from ILC3-dom- purposes. tory is mostly applying X-ray crystallog- inated barrier immunity to ILC2-mediated raphy but also uses NMR spectroscopy and electron microscopy for the structural analysis of protein complexes. Zeinab Abdullah Cluster junior research group

Chronic inflammation in the liver can af- Christoph Wilhelm fect the function of immune cells leading Cluster chair for Immunopathology to impaired immune responses against new pathogenic infections. The research The mucosal immune system maintains focus of the Abdullah lab is on the im- the intestinal barrier in the face of a di- pact of chronic inflammation during liver verse array of challenges, including the fibrosis on the function of hepatic myeloid uptake of nutrition, the interaction with cells and how this effects the host im- commensal microbiota, and the defense mune response against microbial patho- Dr. Zeinab Abdullah against chronic helminth infections and gens during chronic liver inflammation. by Johann Saba, UKB-Ukom bacterial or viral pathogens. An important You can find an interview with Zeinab Ab- component of this barrier defense mech- dullah on page 51. anism are innate lymphoid cells (ILC). ILC are a recently discovered lymphocyte New population, and their functions are not Annkristin Heine Developments yet fully understood. Three distinct ILC Cluster junior research group/ Clinical Prof. Christoph Wilhelm subsets have been reported to reside in translational group - by Johann Saba, UKB-Ukom Member the gut, lung and skin. Type 1 ILC (ILC1) express the transcription factor T-bet, Annkristin Heine and her group are work- produce the cytokine interferon (IFN)-γ ing to improve cytotoxic T cell mediated and are implicated in protecting against anti-tumor responses by harnessing intracellular pathogens such as Toxoplas- cross-presentation. Her clinical transla- ma gondii. ILC2 express the transcription tional research group aims at integrating factor GATA-3 and produce the cytokines laboratory and clinical investigation of IL-5, IL-9, IL-13 and amphiregulin. ILC3 immunotherapies. An additional focus are characterized by the expression of of the Heine group is on understanding the transcription factor Rorγt and the the immunomodulatory effect of novel cytokine IL-22. Christoph Wilhelm found anti-cancer drugs and the molecular and that vitamin A deficiency (a severe form of cellular regulatory mechanisms of immu- Dr. Annkristin Heine malnutrition) leads to the loss ILC3 pro- notherapeutic anti-tumor approaches. by Johann Saba, UKB-Ukom ducing IL-22 but a reciprocal increase in With their work, the Heine lab would like ILC2 secreting IL-13. This switch in ILC to help translate basic research investiga- subsets resulted in impaired anti-bacterial tions into effective cancer treatments. You can find an interview with Annkristin Heine on page 53.

44 45 Marc Beyer Andreas Schlitzer

Marc Beyer and his group are interested The focus of Andreas Schlitzer‘s research in deciphering the molecular mecha- is on the developmental processes lead- nisms governing T cell and myeloid cell ing to the many different forms of special- functionality using modern genomics or ized dendritic cell and monocyte subsets transcriptomics methods, such as ge- during homeostasis and disease. The nome editing via TALENs and CRISPR/ Schlitzer lab approaches this question Cas9 or single-cell transcriptomics, and from different angles with state-of-the-art investigating important epigenetic and techniques, such as single cell mRNA se- posttranscriptional regulations. They em- quencing, multi-colour fish and advanced ploy human cells and model systems to flow cytometry. Understanding the etiol- study the transcriptional events necessary ogy of the different functional states of PD Dr. Marc Beyer Dr. Andreas Schlitzer by Johann Saba, UKB-Ukom for the suppressive activity of regulatory T dendritic cells and monocytes will help by Johann Saba, UKB-Ukom cells. The current focus of their research to identify relevant steps in the onset and New is the role of Satb1, a global chromatin progression of many diseases. Developments organizer and transcription factor, in CD4+ - T cells and the prostaglandin E2 (PGE2) metabolizing enzyme hydroxyprostaglan- Sven Wehner Member din-dehydrogenase (HPGD) in regulatory T cells as well as signal integration result- Sven Wehner and his lab aim to elucidate ing in immune cell exhaustion. the underlying mechanisms of acute and chronic intestinal inflammatory disorders, with a focus on the (neuro)-immunological New mechanisms that contribute to functional Martin Schlee disturbances of the gastro-intestinal tract. Developments Currently, the Wehner lab is investigating - Research in the Schlee lab focuses on the neuroimmunology of chronic inflam- Member understanding the mechanisms of im- matory bowel diseases and how intestinal mune recognition of nucleic acids. Anti-vi- inflammation is triggered. The identifica- ral immune responses rely on nucleic acid tion of novel neuro-immune modulatory Prof. Sven Wehner receptors of the innate immune system pathways is an important step towards by Johann Saba, UKB-Ukom that distinguish pathogenic nucleic acids understanding the mechanisms of acute from endogenous ones. This distinction is and chronic intestinal inflammatory dis- important because an insensitive recogni- eases. tion can lead to increased spread of infection while an excessive immune detection of nucleic acids leads to autoimmune dis- Dr. Martin Schlee by Johann Saba, UKB-Ukom eases. Thus, recognition of nucleic acids relies on the unusual localization, structure or modifications of pathogenic nucleic acids which can be detected by distinct immune receptors. Moreover, to avoid immune recognition, some viruses incur RNA modifications shielding them from recognition by nucleic acid receptors. Recently, Martin Schlee and his group have helped identify and characterize the recognition motifs of cytosolic DNA and a cytosolic RNA receptors as well as viral modifications that can prevent their recognition. You can find an interview with Martin Schlee on page 56.

46 47

Interviews Interview with Dr. Zeinab Abdullah Cluster Junior Research Group Leader

Dr. Zeinab Abdullah Institute of Experimental Immunology

Dr. Zeinab Abdullah, PhD Institute of Experimental Immunology Medical Faculty University of Bonn

Dr. Annkristin Heine, MD Medical Clinic III for Hematology and Oncology and Institute of Experimental Immunology Medical Faculty University of Bonn

Dr. Martin Schlee, PhD Institute of Clinical Chemistry and Clinical Pharmacology Medical Faculty University of Bonn

Dr. Karin Pelka, PhD ImmunoSensation: Zeinab Abdullah: Institute of Innate Immunity You are a new member of the Immuno- Using in vivo mouse models for chronic Medical Faculty Sensation Cluster and group leader of a viral infections that mirror the situation University of Bonn junior research group. What is your main in humans and combined approaches, research focus and how is it related to the such as genomics, bioinformatics and Philipp Schlegel ImmunoSensation Cluster? cellular immunology, we have identified Molecular Brain Physiology and Behavior TNF signaling in T cells to be the under- Life and Medical Sciences Institute (LIMES) Zeinab Abdullah: lying mechanism for T cell dysfunction University of Bonn The overall goal of our research is to during chronic viral infections. Moreover, understand how chronic inflammation we could show that TNFα promotes the Lorenz Omran can affect the outcome of infection and induction of multiple inhibitory pathways immune cell function. Specifically, our related to T cell dysfunction including Carl-von-Ossietzky Secondary School, Bonn research focuses on mechanistic studies PD-1 and CTLA-4. Strikingly, in vivo to understand the impact of chronic liver blockade of TNF using the FDA approved inflammation on the function of hepatic drug infliximab re-invigorated CD4 and myeloid cells and lymphocytes in host CTL function and reduced viral loads to defence and adaptive immune responses background levels. These findings open against de novo infections. new avenues for future therapeutic strategies for chronic viral inflammatory condi- ImmunoSensation: tions with TNFα involvement. You recently published a paper in Nature Immunology. Congratulations! Could you ImmunoSensation: give us a short overview of the major The work was done in conjunction with findings? another Cluster group (Prof. J. L. Schul-

51 tze). How does the ImmunoSensation Zeinab Abdullah: Interview with Dr. Annkristin Heine Cluster foster scientific collaborations? In collaboration with the lab of Prof. JL Schultze we are conducing single cell Cluster Junior Research Group Leader Zeinab Abdullah: RNA-sequencing to be able to dissect the The ImmunoSensation Cluster fosters interplay between intrinsic cellular pro- collaborations and scientific exchange by cesses and extrinsic stimuli such as the organising joint meetings and scientific local environment or neighboring and their retreats in which Cluster PIs can present impact on the outcome of the immune their work, concepts and technologies, responses in the liver. Dr. Annkristin Heine and these can greatly benefit other proj- We would like also to make use of the Medical Clinic III for ects. outstanding expertise of Prof. W. Kast- Hematology and Oncology enmüller in intravital microscopy to gain and Institute of Experimental Immunology ImmunoSensation: better insights on the interaction between How do you think could we further different immune cell population in the . enhance networking and collaborations liver. within the Cluster?

Zeinab Abdullah: In my opinion organizing joint seminars between different groups within the Clus- ter will enable the connection of expert knowledge from different fields, such as neuroscience, bioinformatics & genomics immunology and will make state-of-the- art techniques in these fields available to all scientists involved. All this facilitates fruitful interactions. ImmunoSensation: I believe that my research focus fits well ImmunoSensation: You are leader of a newly established into the Cluster because it offers a direct What kind of advice would you give junior research group within the Cluster. translation from basic immunologic ideas young students who would like to pursue What is the focus of your research and into clinically meaningful therapeutic or a career in science? how does it relate to the Cluster? diagnostic options. And, of course, most of these questions cannot be answered Zeinab Abdullah: Annkristin Heine: without the support of the excellent im- Follow your passion and desire to discov- The aim of my research is the identifica- munologists within the Cluster. er things. Discuss your findings. Don’t be tion of novel immunotherapeutic strat- afraid to question things, and get input egies with a special focus on dendritic ImmunoSensation: from others. Communicate and interact cell licensing and chemokine receptor What advantages do you think will it have with others to move your work forward. modulation. A further interest of mine to work as a researcher within the Immu- Collaborate with others because you will is the monitoring of immune responses noSensation Cluster? not be able to do it all on your own. and immunomodulatory effects of novel anti-cancer drugs in patients and mice. Annkristin Heine: ImmunoSensation: Due to my work as a senior physician at The most striking advantage of being a What future innovation could have the the Medical Clinic III for Oncology, Hema- Cluster member is having the opportunity highest impact on your research area? tology and Rheumatology, I am confront- to meet all of the great immunologists in ed with clinically relevant questions on a the Cluster and establish new, productive daily basis. It fascinates me to translate collaborations. The Cluster provides a these problems into scientific questions really unique and energetic atmosphere. and to try to identify the underlying mech- In addition, becoming part of the Clus- anisms of what I observe clinically. This ter also was a very important step in my kind of research is very inspiring to me. scientific career. It has enabled me to

52 53 start my own junior research group and underlying mechanisms of this process employ a very skilled technician and a and develop new scientific ideas based motivated PhD student. Without them, on careful, detailed observation of my I couldn’t pursue my further career as a patients. clinician scientist, which of course means a lot of time not only in the lab but also ImmunoSensation: in the clinic. Moreover, the Cluster also How do you think could the Cluster en- offers lots of additional support for its courage more women to stay in science? members, such as interesting seminars, great talks and meetings with fascinating Annkristin Heine: scientists. There are great women who are fantastic scientists. However, even though they ImmunoSensation: love their job, a lot of them would like You published successfully in several to start a family one day. In my opinion, different journals in 2015. What was your many women themselves, but also many personal highlight? supervisors, still believe that a woman cannot handle both a family and serious Annkristin Heine: scientific research efficiently. However, I don’t think that it was one, single pub- there are many examples of success- lication but rather the honor of receiving ful women who manage both. For me, the Lisec-Artz-Preis for the best junior personally, it is quite a relief to know that scientist in tumor immunotherapy in 2015 there are attractive offers for child care or that was my personal highlight. Seeing emergency babysitting support within the my work acknowledged was very moti- Cluster. vating. ImmunoSensation: ImmunoSensation: What future innovation could have the Your independent junior research group highest impact on your research area? is associated with the Medical Clinic III for Hematology and Oncology. What do you Annkristin Heine: think are the advantages of working as a When I was first interested in tumor clinician and conducting research in the immunology and vaccination therapies field of immunology? in 2004, many researchers thought that tumor immunotherapy was obsolete. Annkristin Heine: Talks or poster presentations dealing with I love to work as a clinician and do basic tumor immunology at the big congress- research at the same time. In the clinic, es were always during the last sessions the direct contact with patients and their when most attendees had already diseases brings up so many questions checked out. I am happy that I was not and riddles every day. In the laboratory, I too discouraged at the time and stuck to have a great opportunity to discuss these the topic. Now, it is almost overwhelming important questions with basic scientists how big the “hype“ surrounding tumor im- and develop new scientific approaches to munology is. Innovations like checkpoint solving these problems. As an example, inhibitors have fully changed the lives of I treat many patients who have received tumor patients. It is a really exciting time allogeneic bone marrow transplantation, to be in the field! Impression 7th DAMPs and HMGB1 Meeting 2015, Bonn many of whom develop severe graft-versus hose disease. The whole process of stem cell transplantation is a fanatastic example of “pure“ translational immunology, and it is fascinating to understand the

54 55 Interview with Dr. Martin Schlee publish a study while it is still not quite as Papilloma-, Polyoma- and Poxviridae) mature in a journal with less attention to with a double stranded DNA genome but Bonfor Junior Research Group Leader be on the safe side. In some cases, the also viruses that produce single stranded last 10% of the work takes up 90% of DNA, like lentiviruses (e.g. HIV). We found the whole work time. I am really glad and that the sensitivity of cGAS activation by grateful that we were lucky enough to see ssDNA is tremendously enhanced when our hard work and patience rewarded. structures are formed that bear G rich sin- Dr. Martin Schlee gle-stranded DNA adjacent to short base Institute of Clinical Chem- ImmunoSensation: paired structures. Such ssDNA structures istry and Clinical Pharma- What important findings led to your two are formed in the cytosol during the early cology publications in 2015? phase of HIV replication.

Martin Schlee: ImmunoSensation: The projects are described in more detail You have been conducting research as research highlights in this issue (see in Bonn since 2006. How did the Im- page 14). In brief, we found that a simple munoSensation Cluster influence your methylation, which the smallest known research? covalent modification in nature, at the 5’cap of mRNA prevents recognition of Martin Schlee: endogenous RNA by the innate immune One of my PhD students, Ann Kristin receptor RIG-I, a master sensor of viral Bruder, has been funded by the Cluster infections. RIG-I is responsible for the since 2015. She is one of the first authors detection of and antiviral defense against of the manuscript on N1-2’O-Methylation most RNA viruses and initiates a signal- and RIG-I. In addition, many of my collab- ing cascade towards either type I IFN orators are also Cluster members. induction or apoptosis after sensing of viral RNA. Since most cells have RIG-I, ImmunoSensation: ImmunoSensation: infection. However, excessive immune absence of this mRNA methylation would What do you think are emerging topics in What is your main research area, and detection of nucleic acids can lead to lead to a permanent immune stimulation the field of innate immunology? how does it connect to the ImmunoSen- autoimmune diseases such as systemic of all tissues. Of note, this methylation sation Cluster? lupus erythematosus (SLE). My research has no direct impact of RNA dependent Martin Schlee: area immunorecognition of nucleic acid is protein translation. Thus, at the moment, I think that there is still a lot to learn about Martin Schlee: thus directly in the focus of the Cluster of this methylation appears to have mainly how viruses exploit and manipulate post- The focus of my research is the antiviral Excellence ImmunoSensation. immunomodulatory functions and serves transcriptional regulation mechanisms of immune response of the innate immune as a marker of “self” RNA. Another gene expression. system. Here, nucleic acid receptors play ImmunoSensation: aspect of this work was that RIG-I has a particularly central role, in that they 2015 has been a really successful year a highly-conserved, bulky amino acid ImmunoSensation: initiate and control the antiviral immune for you. What was your personal highlight in its RNA binding pocket. This residue What new innovations have had the response of the infected organism. The 2015? is dispensable for RIG-I activation but greatest impact on your research area? detection of pathogenic RNA/DNA by prevents binding of endogenous methyl- nucleic acid receptors is based on rec- Martin Schlee: ated mRNA. Amazingly, this self-tolerance Martin Schlee: ognition of unusual RNA/DNA localiza- We were able to publish two projects in mechanism in RIG-I is 100% conserved A new technique, CRISPR/Cas9, which tion, structure and modifications, also high ranking international journals. How- all the way back to simpler invertebrate exploits a pathway of the bacterial im- known as pattern recognition motifs. ever, these projects were started a couple species like sea anemones. mune system that guides nucleases to The challenge for the innate immune of years ago. The paper about immuno- In another project, we identified a new specific target DNA sequences, has enor- system is that it should, ideally, detect tolerance of endogenous RNA was sub- DNA recognition motif for the cytosolic in- mously facilitated genome editing even in pathogenic nucleic acids as sensitively mitted the first time in December 2010. nate immune receptor cGAS. Like RIG-I, tissue culture cells. This has tremendously as possible, yet also perform this task There is always the question whether you the DNA sensor cGAS is a master sensor accelerated the progress in our research specifically, without false activation by should take a risk and follow a project of viruses, albeit of viruses that generate area in the last years. the endogenous nucleic acids. A lack with high potential until its acceptance viral DNA during their replication cycle. of sensitivity would favor the spread of in a high ranking journal or if you should This includes DNA viruses (e.g. Herpes-,

56 57 Interview with Dr. Karin Pelka Former - PhD Student in the lab of Prof. Eicke Latz

me. Depending on the available resourc- Karin Pelka: ImmunoSensation: es, you have to find the right strategy. I did my PhD under the supervision of If you had unlimited research funds, what With little money, you have to divide your Dr. Karin Pelka Eicke Latz at the Institute of Innate Im- scientific problem would you tackle? big goal into very small and rather safe Institute of Innate munity. I was working on a protein called steps, use affordable technologies, and Immunity UNC93B1. UNC93B1 is a key-regulator Karin Pelka: avoid spending money on risky projects. of nucleic acid sensing Toll-like receptors The amount of funding actually would Unlimited research funds enable you (TLRs). These receptors are crucial in the not change what I want to work on. I to use high-end technologies, take on host defense against viruses and bacte- am fascinated by the complex regulation projects on any scale, check out creative ria by sensing pathogen-derived nucleic of immune responses. The fact that the shortcuts, be bold, share openly, and go acids. Detection of host-derived nucleic immune system plays a crucial role in for high-risk high-gain projects. If done in acids, however, can lead to autoinflam- many diseases such as infectious diseas- a clever way, this can of course greatly matory diseases. During my PhD, we es, autoimmunity, metabolic diseases, accelerate your research. I was very lucky looked into the mechanisms by which and cancer, makes it a very relevant and to do my PhD with Eicke Latz where I got UNC93B1 regulates these TLRs. We versatile research topic. Having unlimit- some sense for this second approach made some quite unexpected discoveries ed research funds would mostly change towards science. Now, I am very excit- which we currently try to publish. how I perform research. In many ways, ed and slightly scared to join the Broad science feels a little bit like gambling to Institute where this approach is taken to ImmunoSensation: another level. What do you think were the benefits of conducting your PhD in the ImmunoSen- sation Cluster? Interview with Philipp Schlegel ImmunoSensation: Karin Pelka: Karin, you just finished your PhD in the I was already quite far in my PhD when PhD student in the lab of Prof. Michael Pankratz lab of Prof. Eicke Latz. What brought you the Cluster graduate program (IITB) with to Bonn? all the workshops and seminars started. I would definitvely advise future genera- ImmunoSensation: Karin Pelka: tions to make use of these offers. For me, You conducted your PhD thesis at the I came to Bonn to study Molecular Bio- the benefits were mostly to be among Life and Medical Sciences Institute. What medicine. Back then, not so many univer- highly motivated people who work on brought you to Bonn in the first place? sities offered a study program like this. To a wide variety of scientific aspects and Philipp Schlegel be honest, coming from the south of Ger- have complementary expertise. I was also Philipp Schlegel: Department for many, universities like Freiburg, Erlangen involved in organizing a Cluster Girls’ Day I did my Diploma in biology in Bonn and Molecular Brain Physiolo- or Ulm were on the top of my list initially. and a Cluster Night of Science which was by the time I finished my thesis in the lab gy and Behavior (LIMES) However, during the interviews, Bonn just fun. of Prof. Pankratz working with the lab had blew me away. I could feel the passion been a lot of fun but the projects between for science, the excitement for this new ImmunoSensation: me and my colleagues were just about to study program, and the great atmosphere Where are you heading now after finishing really take off. Fortunately, Prof. Pankratz among the students. your PhD? offered me a PhD position and so I decided to stay and follow up on the findings of ImmunoSensation: Karin Pelka: my diploma thesis. Tell us a bit more about your PhD. What To Boston. I am very excited to do my was the main research focus of your doc- postdoc in Nir Hacohen’s lab at the Broad ImmunoSensation: toral thesis? Institute. What was the main research focus of

58 59 your PhD in Prof. Pankratz’ lab? ImmunoSensation: Where are you heading now after finishing Philipp Schlegel: your PhD? The lab collaborates with scientists from the U.S. to generate a map of the wiring Philipp Schlegel: of the larval Drosophila brain, a so-called I will be joining a team of scientists in connectome, based on EM-sections of Cambridge who want to tackle the adult an entire nervous system. I reconstructed Drosophila brain similar to what I did for and analyzed the circuitry for neurons that my PhD in the larva. For starters, I will produce a conserved neuropeptide which train and supervise a team of people that is involved in the regulation of a range of are going reconstruct the connectome of behaviors, including pathogen avoidance. the adult fly. With these data we are going to investigate the circuitry that is involved ImmunoSensation: in learning, memory and innate behavior. What do you think were the benefits of conducting your PhD in the ImmunoSen- ImmunoSensation: sation Cluster? If you had unlimited research funds, what scientific problem would you tackle? Philipp Schlegel: I am a neurobiologist at heart. Con- Philipp Schlegel:

sequently, it comes natural to me to There is an infinite number of scientific Lorenz Omran working in the lab approach the topic of brain-immune problems that are in dire need of scientific interactions from the brain’s point of view attention. But instead of focusing on a but it also means that I am less familiar single one of them, I’d rather invest into with immunology. This is why the various modernizing the way scientific research is the idea of combining medicine and that it got more and more interesting. workshops, meetings, etc. organized by conducted: create incentives to publish chemistry very attractive. And, since I live The most exciting thing was that I was the ImmunoSensation Cluster have been everything (including negative results) as close to the University Hospital in Bonn, allowed to take part in real scientific re- tremendously helpful to get in touch with open-source and open-access, improve I decided to try and send an application search and that the team, who made me experts in this field and discuss how the the reviewing process, establish more to the Institute of Clinical Chemistry and feel as if I really was part of it, were the brain integrates immune-relevant sig- meaningful metrics than the journal im- Clinical Pharmacology. Prof. Hartmann first to ever discover these things, which nals to initiate an appropriate behavioral pact factor - to name but a few. was so kind as to offer me the chance I think is a great feeling, even if it’s just a response. to take part in one of his team’s projects. small part in the overall research. The project sounded very interesting, so I gladly accepted his offer and started ImmunoSensation: reading about this particular area of im- What was the topic of your “Facharbeit” Interview with Lorenz Omran munology, the STING/cGAMP pathway. and what results could you find? ImmunoSensation: Lorenz Omran: Carl-von-Ossietzky Secondary School Bonn How did you like working in an immunolo- The title of my term paper was: “Einfluss gy lab and what about it in particular? oxidativer Veränderung von DNA-Oligo- nukleotiden auf die Immunantwort”. In a ImmunoSensation: I chose to write my “Facharbeit” in a Lorenz Omran: nutshell: DNA in cells belongs mainly in You decided to pursue research for your scientific field. However, I really wanted to At first, it was quite challenging and the nucleus, but definitely not into the cy- eleventh-grade term paper (Facharbeit) in do something new and hands-on rather sometimes a bit frustrating to learn how tosol. Therefore, whenever a cell detects the lab of Prof. Hartmann. How did you than summarizing theoretical things that limited my school knowlege in biology DNA in its cytosol, it is usually a sign for a get the idea to work in a real lab, and why have already been discovered. And, since really was, and the English scientific viral infection and is fought by an immune did you pick the topic of immunology and it turned out that such a project would be terminology didn’t make it easier, but with response. The goal of the study was to Prof. Hartmann’s lab? impossible at my school, I started look- the support of Prof. Hartmann and Dr. come up with a DNA-oligonucleotide ing for an alternative. I’m also interested Herzner, one of his team members --and which stimulates the immune response Lorenz Omran: in medicine and had already done an also motivation from my girlfriend and my and thereby strengthens the autoimmune Chemistry is one of my main subjects, internship in a large medical device com- family-- I started to make progress in my system. Recent research showed that the and it’s also my favorite one. That’s why pany (Medtronic) in Maastricht. I found understanding of the subject and found y-stem structure of the DNA-oligos in the

60 61 early HIV virus was highly stimulatory. We Lorenz Omran: tested seven different modifications, using Luckily, I still have one more year at human white blood cells and measured school, as I don’t yet know exactly what the interferon levels to determine the I want to do afterwards. However, I know immune response. As a conclusion, one for sure that I want to work in the area of can say: different modifications of the natural sciences. oligos differed in their stimulating effects, depending on the concentration of the ImmunoSensation: oligos in the cells. After experiencing the working atmosphere in an immunology lab, can you ImmunoSensation: imagine yourself being a scientist? You are finishing school now. What are your plans afterwards? Lorenz Omran: I definitely find the idea of working in a scientific lab very attractive.

Impressions Cluster Science Days 2015

62 63 64 65 Cluster Coordination Events

The Cluster Coordination Office is in and family support and public relations. Report charge of the implementation and financial Within this section, we would like to give administration of Cluster events, the coor- an overview of the organized events for dination of the graduate program, gender students and Cluster scientists.

7th DAMPs and HMGB1 Meeting th 3rd Cluster Science Days ImmunoSensation hosts 7 International Joint ASI-DGfI Workshop Canberra Symposium on DAMPs and HMGB1 September 10-12, 2015 Establishment of the DFG-funded IRTG “Bo&MeRanG“ with Melbourne, Australia

International Immunology Training Program Bonn (IITB) Background Family Support & Gender Equality Damage (or danger)-associated molec- immune response. However, excessive 7th International Public Relations ular pattern molecules, or DAMPs, are or inappropriate HMGB1 release has also DAMPs and endogenous molecules, such as proteins been implicated in the sterile inflammatory HMGB1 Symposium Cluster Seminars and Seminars of Cluster Cooperation Partners 2015 and nucleic acids and metabolites, which processes associated with many human can function as pro-inflammatory danger diseases, including ischemia, immune Cluster Meetings 2015 signals upon changing their subcellu- disorders, neurodegenerative diseases, lar localization or after their release into metabolic disorders, and cancer. the extracellular space. As endogenous The International Symposium on DAMPs stress signals, DAMP release and sensing and HMGB1 was established by the in- are pivotal to the initiation and perpetua- ternational HMGB1 group of scientists tion of the inflammatory response, both with the goal of better understanding the in sterile inflammation and in the host mechanisms of DAMP and HMGB1 bi- defense against pathogens. High-mobility ology and their implications for disease. group box 1 (HMGB1) is a prototypical This year was the first time that Bonn was DAMP. Inside the cell, HMGB1 is a nucle- selected to host the symposium, and all ar protein that participates in chromatin of the local organizers, including Gunther remodeling and transcriptional regulation. Hartmann (local chair), Michael Hoch, However, upon a variety of physico- Waldemar Kolanus, Christian Kurts, Eicke chemical or biological insults, HMGB1 Latz and Andreas Zimmer, are members is released into the extracellular space, of ImmunoSensation. We are very proud where it triggers inflammatory responses that the Cluster was given the opportunity via its receptors TLR2, TLR4 or RAGE. to host such an important meeting and Via these pathways, HMGB1 can induce that we could welcome so many interna- dendritic cell maturation, the production tionally renowned experts in innate immu- of pro-inflammatory cytokines, and the nity to Bonn, including Charles Dinarello, upregulation of the expression of cell ad- Tak Mak and Kevin Tracey, who all agreed hesion molecules, processes vital to the to be keynote speakers.

67 by Tak Mak, who described HMGB1 as Poster awards a “double-edged sword” in inflammation. The final session of the day focused on Selina K. Fassl, Institute of Immunolo- DAMPs in tumor immunology and was gy, University of Münster, Germany for chaired by the noted thoracic oncologist, the poster entitled “Pyrin and PSTPIP1, Michele Carbone. The keynote address mutated in FMF, PAPA-, and PAMI syn- th 7 International by Michael Lotze was “HMGB1, Cancer drome, are involved in the hypersecretion Symposium on and Immunity: RAGE, rage against the of DAMPs MRP8/14” DAMPs and dying of the light”. Ravikumar Sitapara, Department of After the sessions, a podium discussion Pharmaceutical Sciences, College of HMGB1 on HMGB1 and IL-1 sought a consensus Pharmacy and Health Sciences, St. on how those two related DAMPs mol- John’s University, Queens, NY, USA for ecules impact the immunopathogenesis the poster entitled “The α7 nicotinic ace- of acute and inflammatory diseases. In tylcholine receptor agonist GTS-21 atten- the evening, the official conference dinner uates hyperoxiainduced acute lung injury and party was hosted at the Godesburg, by decreasing hyperacetylation and the Bad Godesberg, Bonn, leaving the partic- release of nuclear HMGB1” ipants with colourful impressions of Bonn Thomas Zillinger, Institute of Clinical and its surroundings. Chemistry and Clinical Pharmacology, University Hospital of Bonn, Germany for Day 3 the poster entitled “ADAR1 controls recognition of self-RNA by MDA5” On the final day of the th7 International th Symposium on DAMPs and HMGB1, the This wrapped up the official part of the 7 International meeting moved to an extraordinary loca- meeting, but the social activities contin- Symposium on tion: the “Wasserwerk”, the former plena- ued. The Cluster organized bag lunches DAMPs and Day 1 Glycation Endproducts (RAGE), which is ry hall of the German Federal Parliament. and bikes for a long tour along the river a major receptor for HMGB1 and other ImmunoSensation invited all participants Rhine. The tour ended at the Chairman’s HMGB1 On Thursday, September 10, Gunther DAMPs. The evening offered not only a to discuss clinical and therapeutic impli- private house, where everyone was invit- Hartmann officially opened the meeting spectacular view of the Siebengebirge cations of DAMPs and HMGB1. This his- ed to a barbecue garden party. and welcomed the participants to the and fantastic food but also lively scientific toric location was also used to confer the The next International Symposium on Biomedical Center at Bonn Venusberg. discussions and great expectations for poster awards. DAMPs and HMGB1 will take place in The first session then began with Ulf the two days to come. Liverpool in 2017, and we are sure that Andersson’s keynote address, which many Cluster members will attend. provided fascinating insight into current Day 2 research and open questions about HMGB1 biology. Afterwards, the session Friday, September 11, was all about then continued with a variety of talks on DAMPs, their immunobiology, and their the structure and function of HMGB1 with clinical implications in sterile inflammation a focus on its role in health and disease. and tumor immunology. The first session The first day concluded with the speak- of the day was chaired by the HMGB1 ers’ dinner cruise along the river Rhine. expert Helena Erlandsson and focused While enjoying the beautiful sunset, Mar- on DAMPs and sterile inflammation. The co Bianchi was awarded the Angelika Bi- session began with an excellent keynote erhaus Memorial Award for his outstand- address from Charles Dinarello, who ing contributions to our understanding of offered a new perspective on the role the biology of HMGB1. Prof. Dr. Angelika of IL-1α as a DAMP in conjunction with Bierhaus, University of Heidelberg, devot- the inflammatory response to HMGB1. ed her life to understanding the molecular The next session was on the immuno- mechanisms of chronic diseases and biology of DAMPs and was chaired by discovered that many of these were as- the eminent TLR researcher, Hermann sociated with the Receptor for Advanced Wagner. The keynote address was held

Bike Tour on Day 3 68 69 3rd Cluster Science Days 3rd Cluster Science Days November 2- 3, 2015 November 2- 3, 2015

Best Talk:

Best Poster:

Donald Guu ‘Space and Time in Leukocyte Migration’

Jesuthas Ajendra Lorenz Fülle informal get-together. IITB students from ‘NOD2-/- mice are more susceptible ‘Inflammation dependent upreg- all groups used the opportunity to discuss to infection with Litomosoides sog- ulation of CCL17 in hippocampal how to be successful in the highly com- modontis due to an impaired early neurons and its influence on neu- petitive world of science. As usual, the protective immune response’ ro-immune interactions’ posters and talks from the participants were of excellent quality, and it was diffi- cult to decide who should win the poster Monika Plescher and talk prizes. This year we wanted to ‘Establishing single-cell transcrip- Organization Committee involve the audience more in the decision tomic analysis of microglia in Alzhei- process, and the poster prizes were dem- mer’s disease’ The Cluster Science Days have been held excellent overview of the current research ocratically chosen with all participants every year since 2013. This intramural sci- topics within the Cluster and were also voting. entific meeting is firmly focused on young complemented by keynote addresses rd 3 Cluster scientists and their research, offering a and poster sessions for each area. One Science Days forum for young investigators to network of the new features implemented by the and exchange ideas. This year, the Steer- organizing team was a technical ses- ing Committee decided to entrust several sion to introduce the work of the Cluster PhD students and young postdocs with platforms and to offer a close-up look at the organization of the 3rd Cluster Science new technical developments within the Days, which was a great success. labs of the Cluster groups. The sessions This year 85 abstracts were submitted by helped to enhance exchange of technical young scientists, from which 25 talks and knowledge and technical expertise be- 23 speed talks were selected. These talks tween all participating Cluster scientists. were organized according to the research Another new feature were the evening areas within the Cluster, which, in itself, events implemented to give PhD students was a daunting task. Over the years the possibility to discuss scientific career the Cluster research areas have “grown options. Internationally recruited group together” and many research projects leaders and professors from the Cluster incorporated aspects of several areas and some of the Cluster‘s alumni were at once. Nonetheless, the talks gave an invited for round table discussions and an f.l.t.r.: Prof. Gunther Hartmann, Lorenz Fülle, Monika Plescher, Jesuthas Ajendra, Dr. Donald Guu and Prof. Waldemar Kolanus

70 71 Joint ASI-DGfI Workshop Canberra (AUS) Establishment of the DFG-funded IRTG December 3- 4, 2015 “Bo&MeRanG“ with Melbourne, Australia

by Prof. Christian Kurts 2016. Bo&MeRanG stands for Bonn & Melbourne Research and Graduate Train- Cluster scientists have teamed up with ing group. The topic synergizes with the leading immunologists from Melbourne Cluster of Excellence “ImmunoSensation”, University, the premier University of which focuses on the innate immune Australia, to establish an International response in sterile inflammation. The Research Training Group (IRTG) for PhD Cluster boasts great expertise on immune students. Participants will receive instruc- sensors and molecular and transcriptional tion from scientists from both universities. immune regulation, whereas Melbourne is The common research focus within the a leading international center in the field of program is the acquired immune defense immunological defense against infection against infections, which ideally com- and in research on rare immune cell pop- plements the expertise of “ImmunoSen- ulations. Combining these areas of ex- sation”. The DFG will fund this new joint pertise will allow the scientists to perform international graduate college “Bo&MeR- more effective research and broaden the anG” at the Universities of Bonn, and teaching curriculum in immunology and Melbourne for 4.5 years starting in April infectiology. The new graduate school

Delegates of the first joint ASI-DGfI Workshop in Canberra, Australia

The first joint workshop of the German meeting, fostering new German-Austral- and the Australasian Societies for Immu- asian scientific collaborations, and full of nology was held in Canberra, Australia inspiring discussions. In particular, the under the joint organization of Christian application of stochastic modeling has Kurts and Catherine Drescher (Immuno- led to a re-evaluation of “old, accepted Sensation) and Sammy Bedoui (University truths” in the field, such as the asymmet- of Melbourne) and Anselm Enders (Aus- ric cell division model. tralian National University). The workshop The focus of the joint workshop was “im- was associated with the 45th Annual Sci- mune regulation in infections and immune entific Meeting of the ASI, held from Nov mediated diseases”, with delegations of 29-Dec 3, 2015 in Canberra. The second outstanding German and Australasian ASI-DGfI meeting will be held in conjunc- immunologists in attendance. A full meet- tion with the annual DGfI meeting in 2017 ing report can be found in the European in Erlangen. Journal of Immunology, Volume 46, Issue Signing the joint teaching agreement in Melbourne, February 2015. The satellite ASI-DGfI workshop was the 2, pages 265–268, February 2016. Standing from left to right: Geoff McColl (Head of Melbourne Medical School), Dick Strugnell (Pro-Vice Chancellor for Graduate Research, University of Melbourne), Max Baur (former Dean of the Bonn Medical perfect follow-up to a very successful ASI Faculty), Nicolas Wernert (President of the Senate of the University of Bonn, now Dean of the Bonn Medical Faculty), Jim McCLuskey (Vice Chancellor, University of Melbourne). Seated from left to right: Liz Hartland (Head of the Dept. of Microbiology & Immunology, Melbourne), Sam- my Bedoui (Bo&MeRanG Co-Speaker, Melbourne), Christian Kurts (Bo&MeRanG speaker. Bonn), Ian van Driel (Associate Dean, Melbourne School of Graduate Research)

72 73 will be located at the ImmunoSensation can be supported by this internation- headquarters at the Bonner Institutes of al-class doctoral program, thanks to the International Immunology Training Immunology and Infectious Diseases (BI3) funding by the DFG and the Universities in the planned BMZ II research building of Bonn and Melbourne. This program of Program Bonn (IITB) to be erected from 2017 on the Venus- scientific exchange between Bonn and berg. According to Prof. Christian Kurts, Melbourne will not only advance science, the speaker of the graduate school: “The but will also provide the graduate stu- The International Immunology Training tion Blog.The first round of travel fellow- synergistic combination of the exper- dents involved with the opportunity to live Program Bonn (IITB) continued its great ships was granted in October 2015 to the tise of outstanding scientists from the and work in the partner country.” After range of scientific and social activities to following IITB members: Universities of Bonn and Melbourne is successful completion of the program, offer in 2015. In addition, we were also a great advantage in the international students will receive a joint PhD (Doctor able to expand our program in 2015. The Sarah Eickhoff, Kastenmueller lab, CFCD competition for outstanding students of Philosophy) title from both universities. IITB now also offers travel grants, the stu- Annual Meeting: DC ontogeny, functional and excellence in research, because it The common-research theme of the new dents’ network day and scholarships for specialization and targeting, Paris, France International will give our students an even better ed- Research Training Group are ‘myeloid the DGfI Autumn School. ucation and research opportunities.” He antigen presenting cells’ (APC) and their Alena Grebe, Latz lab, Toll 2015 Targeting Immunology knows Melbourne and the immunologists control over T lymphocytes. This interac- 1. IITB Travel Grants of Innate Immunity, Marbella, Spain Training there well, because he received his own tion is essential to the adaptive immune Program Bonn immunological training at the Walter and response and is required for both vacci- IITB students can now apply for travel Christoph Heuser, Kurts lab, CD1-MR1, (IITB) Eliza Hall Institute in Melbourne almost 20 nation and pathogen defense. In addition, fellowships granted twice a year on a Mantra Lorne, Australia years ago. The students will spend about dysregulation of this process has been competitive basis. These fellowships are 2/3 of their PhD studies in one of the 15 implicated in many autoimmune and au- offered to promote scientific exchange Florian Hoss, Latz lab, Toll 2015 Targeting participating immunological laboratories toinflammatory diseases, including type I and give IITB students the opportunity to of Innate Immunity, Marbella, Spain in Bonn and one third, at least 1 year, in diabetes, atherosclerosis, kidney and liver present their Cluster-related research to an international audience. We now offer Katarzyna Jobin, Kurts lab, Kidney Week, three different forms of travel grants: San Diego, USA Travel grant 1: Scientific exchange IITB members working in a Cluster lab- Patricia Korir, Hoerauf lab, European con- oratory can apply for travel grant to visit gress of Immunology, Vienna, Austria a lab abroad to learn a new method or technique that is important to their proj- Bettina Nadorp, Soreq lab (Israel), Immu- ect. noSensation workshop “Data Analysis” Travel grant 2: Meetings and Seminars Bonn, Germany Pro-Vice Chancellor Dick Strugnell, Melbourne, The Peter Doherty Institute for Infection and Immu- IITB members who wish to participate in and Dean Nicolas Wernert, Bonn nity at the University of Melbourne an international meeting to present their Stefanie Riesenberg, Hoelzel lab, Society data and broaden their scientific network for Melanoma Research, San Francisco, a partner laboratory in Melbourne. Sci- infections and multiple sclerosis. Thus, can apply for this type of Cluster travel USA entists have designed “tandem research the myeloid APC / T-cell interaction is grant. The Cluster offers financial support projects”, which cover topics that require of great interest for both basic science to cover travel costs and participation Juan F. Rodriguez Alcazar, Latz lab, Toll the expertise of the both laboratories. The and the development of therapeutic ap- fees. 2015 Targeting of Innate Immunity, Mar- students are trained in two disciplines proaches. The more than 30 scientists Travel grant 3: Blog support bella, Spain and benefit from the strengths of two involved in “Bo&MeRanG” have greatly The Cluster also offers support to non- research universities and of their coordi- contributed to our knowledge in this field IITB members like Master’s students or Shani Shenhar-Tsarfaty, Soreq lab (Israel), nated teaching programs. A similar PhD In early spring 2016, the first cohort of 15 young postdocs from Cluster groups. ImmunoSensation workshop “Data Analy- program will be set up at the University German and 15 Australian students will This travel grant is used to promote other sis” Bonn, Germany of Melbourne, led by the German-born be recruited and start to work on their young Cluster scientists outside of the scientist Sammy Bedoui, who trained at tandem projects. While some will start in IITB and encourage them to participate If you want to read about the experienc- the Hannover Medical School. The stu- Bonn, others will depart immediately for the in the newly established ImmunoSensa- es of the travel grant recipients, you can dents from Melbourne will come to Bonn other side of the globe. Regardless, true to tion Blog. Cluster scientists can apply visit the ImmunoSensation Blog on http:// while the German students are doing the name of the program, they will all leave for financial assistance for research visits www.immunosensation.de/blog/. We look research Downunder. According to Dr. Bonn, go to Australia and come back again abroad or an international meetings if they forward to continuing the travel grant pro- Bedoui, “We are extremely pleased that --hopefully taking new knowledge and great are willing to write about their experiences gram in 2016. our long-standing scientific cooperation memories of Australia back with them! there afterwards for the ImmunoSensa-

74 75 International Immunology Training International Program Bonn (IITB) Immunology Training Program Bonn 2. IITB students’ network meeting and a “Young Academy”, which gave PhD (IITB) students the opportunity to talk to experi- The Cluster hosted the first IITB students’ enced postdocs about challenges on the network meeting in May 2015. The net- way to finishing their PhD. The integrated work meeting was jointly organized by soft skill workshop “Elevator pitch”, the the Cluster Coordination Office and a “Young academy” and the social evening team of IITB students. The purpose of afterwards were all very popular. Due to In addition to these new developments, this meeting was to enhance networking the success of the meeting, we now plan the IITB program continued its well-es- between IITB students, inform students to offer it on a yearly basis. tablished meet-the-experts events, the about new IITB activities and workshops Career Café and its scientific and soft skill workshops. Furthermore, some of the

Figure 1 Countries (orange) IITB PhD students originate from.

3. The “International” in IITB the number of international PhD students 4. Cooperation with the DGfI Autumn was our successful establishment of the School IITB members come from many different DFG-funded international graduate train- in immunology”, hosted annually by the countries (Figure 1). The level of interna- ing group “Bo&MeRanG”. You can read In today’s scientific environment, pioneer- German Society of Immunology (DGfI). tionalization is roughly 25%, and the trend more about this initiative on page 73. In ing research can only be performed by In October 2015, ImmunoSensation sent is rising. ImmunoSensation would like addition, we have also been able to offer highly interdisciplinary teams. Reflecting 10 outstanding PhD students to partici- International to foster international exchange in both our long-term partners from the Edmund the diversity of the Cluster, IITB students pate in the Autumn School in Merseburg. directions: (1) PhD students are recruited and Lily Safra Center for Brain Sciences also have very diverse backgrounds in The registration fee and travel costs for Immunology via internationally visible networks and job (Hebrew University Jerusalem) the oppor- life and medical sciences, ranging from these students were provided for via trav- Training announcements like the DAAD support- tunity to participate in the IITB workshop biochemistry, pharmacy, biology and el fellowships. In return, these students Program Bonn ed PhDGermany, Euraxess or Academic “Data Analysis” and to present their work biomedicine to mathematics and bioinfor- presented their research at the Autumn (IITB) Keys; (2) to prepare German PhD stu- on cholinergic signalling and regulation matics, and it is important to give these School, and they are also expected to dents for an international work environ- in inflammation in a mini seminar series students the opportunity to advance share their newly acquired knowledge ment, the Cluster offers IITB travel grants on December 9, 2015 in Bonn. A short their skills and acquire a structured back- with other IITB members. After receiving and actively supports IITB members that report how our guests from Israel have ground in immunology. In addition to the extremely positive feedback from the par- are looking for research opportunities experienced their trip to Germany, the seminars offered to IITB students in Bonn, ticipants in the 2015 program, the Cluster abroad. workshop and the seminar series can be the Cluster has started a cooperation with has decided to continue this cooperation One important measure taken to increase found on page 80. the Autumn School on “Current concepts in 2016.

76 77 International Immunology Training International Immunology Training Program Bonn (IITB) Program Bonn (IITB) International

Immunology In addition to these new developments, IITB students have started a Stammtisch Training the IITB program continued its well-es- and a discussion group the “Immunolo- Program Bonn tablished meet-the-experts events, the gy Study Group”, a student initiative to (IITB) Career Café and its scientific and soft skill review the most important concepts of workshops. Furthermore, some of the innate and adaptive immunity.

August 20, 2015 September 24, 2015 Career Café Miltenyi Presentation Skills Workshop Dr. Rick Scavetta

by Immunology Study Group

WHAT: Immunology Study Group

WHEN: every week Wednesday, 6-7 pm

September 28, 2015 October 05, 2015 WHERE: BMZ, first floor A group member, who is in charge of pre- Adobe Illustrator Workshop Meet-the-Expert paring a previously assigned topic and or- Dr. Kristina Koch Prof. David Tarlinton WHY: The Immunology Study Group is a ganizing a discussion around it, chairs ev- Walter and Eliza Hall Institute of Medical self-organized weekly meeting that aims ery meeting. Topics are picked up based Research to improve and enhance the common on the structure of the book “Janeway’s knowledge of its members in immunol- Immunobiology” from Kenneth Murphy. ogy. It is prepared by and for PhD and After completing every part of the book, International Master’s students who want to learn the field is deeper explored by selecting Immunology more about immunology, as well as have a pile of further reading about the most Training a wider perspective of the field to bet- interesting discussed topics. With the aim ter develop their own research. People of solving some of the posed questions Program Bonn attending the sessions have diverse ex- during our discussions, we plan to host a (IITB) pertise, which gives every member the meeting with experienced scientists who October 26, 2015 opportunity to learn from the other. can clarify these issues. Career Café Participants

78 79 to learning “R” that we had never expe- and “CholinomiRs: From anxiety and Field Report: Data Analysis Workshop rienced before. By using our own data inflammation to humanized Cholinergic for the analysis during the workshop, we regulation in mice”, respectively. We were From Jerusalem to Bonn: Workshop with Dr. Rick Scavetta were able to achieve new insights into our really excited to present our data and data with the skilled help of Dr. Scavetta. got very good feedback and advice from by Dr. Shani Shenhar-Tsarfaty and Bettina Nadorp After the workshop, we really felt like we Cluster members and students. We also International had actually achieved our motivational enjoyed our dinner with Cluster members Immunology goal, and we can now start using “R” for and could benefit from fruitful discussions Training We are both members of the laboratory of terrorism. Bettina Nadorp is a PhD analyzing our own data in a fast and ef- and planning of future collaborations. Program Bonn of Prof. Hermona Soreq at The Hebrew student in the laboratory. Her research fective manner. On the evening of the last Altogether, we had a really great time in University in Jerusalem, Israel, which is interests involve microRNAs (miRNAs) day of the workshop, we held a Cluster Bonn, and we would like to thank the (IITB) part of the International ImmunoSensa- in brain-immune communication, and seminar hosted by Prof. Heneka. We both leadership and members of the Immuno- tion Cluster, Bonn. Last autumn, we were specifically miRNAs that contribute to presented some recently published data Sensation Cluster for enabling us to be awarded with Cluster Travel Fellowships the regulation of the cholinergic signaling and ongoing projects, and our talks were part of this workshop and for giving us in order to attend a highly relevant work- pathway. Many of these miRNA regula- titled “The Cholinergic signaling impair- the opportunity to present our work. shop organized by the International Im- tors are primate-specific (Nadorp and ment in neuro-inflammatory syndromes” munology Training Program Bonn (IITB) Soreq, 2014). Bettina’s work is primarily on the topic of “Data Analysis”. In addi- focused on the primate-specific miRNA tion, we were invited to give a talk on our hsa-miR-608 (Hanin et al., 2014), but also research interests and to have dinner with includes other evolutionarily conserved Cluster members. This is a report on our miRNAs, such as miR-132. Currently, Rappaport Prize for Prof. Soreq - Tel Aviv experiences and interactions with Cluster Bettina is working on the characterization members during our visit to Bonn. First of of a ‘humanized’ transgenic mouse strain all, we would like to introduce ourselves, carrying the primate-specific microR- our research interests, our goals when NA-608 and its human-derived acetylcho- attending this workshop and the focus linesterase binding site. Our motivation of research at the laboratory of Hermona for attending the data analysis workshop Soreq, where we both work. In Prof. Her- was learning how to better cope with mona Soreq’s laboratory, we are focusing large data sets, such as high-throughput on the molecular regulators of human sequencing data or large cohort studies. stress reactions that enable immediate The workshop was a very intense, three survival yet entail long-term damage days’ training for graduate students of spanning neuromuscular, neurodegener- the ImmunoSensation Cluster in Bonn. ative, and inflammatory diseases. More During this workshop we learned how specifically, we are interested in the brain- to use the “R” statistical programming Rappaport Prize Ceremony March 15, 2015 to-body communication pathways that environment for data analysis purposes. control the cholinergic signaling, which Throughout the workshop, instructor Dr. Numerous awards and honours mark University of Stockholm, Sweden, an plays a causative role in these immediate Rick Scavetta taught us not only how to Professor Hermona Soreq’s achieve- honorary professorship in the Maimonides reactions and in many diverse diseases. perform data manipulation and statistical ments, including the Kay Prize for Inno- University, Buenos Aires, Argentina, and Dr. Shani Shenhar-Tsarfaty is a PostDoc modelling but also how to “think” in R, vative Research, the U.S. Army Science completed her post-doctoral studies at in the laboratory. Her research focuses i.e. building our result files in the best way Award for Excellence, Chancellor’s Distin- Rockefeller University, in New York. Prof. on the bio-medical aspects of the cholin- for future statistical analysis, and gave guished Lectureship from the University Soreq was nominated for the Rappaport ergic system and involves genomic and us hands-on experience in analyzing our of California at Berkley and the Israeli Prize for Excellence in Medical Research. biochemical analyses of human volunteer own data. The workshop was structured Ministry of Health Prize for Excellence in The prize was presented at the Tel Aviv cohorts as well as molecular biology in- so that it was interesting from the begin- Biomedical Research. Prof. Soreq has Museum of Art on March 15, 2015. The terference studies in live mice and cell ning to the end. Instead of starting with published over 200 peer reviewed re- prize was established by the Rappaport cultures. In her current research, Shani the very basic language, Dr. Scavetta search papers in internationally acclaimed family to promote visionary, ground- explores cholinergic regulation at different showed us from the beginning how we journals, book chapters and monographs. breaking and innovative research with post-transcriptional levels in multiple clin- can use “R” for the purpose of analysis Prof. Soreq holds a PhD degree in bio- therapeutic ramifications that significantly ical models such as stroke, myocardial with highly motivating hands-on training. chemistry from the Weizmann Institute, promote human health. infarction, metabolic disorders and fear This is a completely unique approach an honorary PhD in Chemistry from the

80 81 Teaching ‘big data’ to young scientists Students’ Initiative: IITB Blog Prof. Joachim Schultze on how to teach young immunologists The ImmunoSensation Blog connects the Cluster’s young investigator community

by Klara Höning One of the major assets of the Cluster is In this article, major considerations for the use of cutting-edge genomic tech- scientists interested in big data immunol- International nologies and computational approaches ogy are provided. These include learning to better understand immune cell type a computer language, participating in Immunology and function, and one of our important special undergraduate and graduate Training goals is teaching young scientists these courses in computational biology, ge- Program Bonn techniques in genomic and computational nomics and systems immunology, un- (IITB) biology. In a commentary for Nature Im- derstanding the big data–driven circle of munology, Joachim L. Schultze outlines systems immunology, attending summer the structural and educational changes or winter schools on computational biol- Pursuing your PhD in the ImmunoSen- cellence using new media formats. The required to educate young scientists in ogy, and spending time on computational sation Cluster of Excellence can be so “Event” posts, reporting about the Cluster high-throughput technologies. Teaching skills. much more than just pipetting and toiling Science Days and research abroad, have ‘big data’ analysis to young immunolo- in the lab from before sunrise to long af- also received a lot of attention. Further- gists. ter sunset. Inspired by the wish to learn more, a survey among the blog’s readers more about what is going on within the returned us very positive feedback on the Cluster and to bring the young investiga- articles as well as the webpage design. Schultze JL. Nat Immunol. 2015 tors together to a lively community we, a The readers also commented on their Sep;16(9):902-5. doi: 10.1038/ni.3250. team of enthusiastic PhD students, start- interest on articles featuring research ed the ImmunoSensation Blog in spring and people from the ImmunoSensation 2015. With the ImmunoSensation Blog Cluster or Cluster events. One important we have established a platform for young ongoing goal for us as the blog team is investigators and everyone interested in to further strengthen the young investi- immunology to explore the diverse range gators’ network with additional events of topics, knowledge and people with- and personal meetings beyond the online in the Cluster. Furthermore, we want to platform. The next main challenge will make people aware of all the fantastic be to spread the idea and to get more opportunities the Cluster is offering for Cluster students and members involved our research and scientific careers. Last in the project. We have already started a year, the newly started blog connected campaign to create more awareness of scientists from all over the world. It had the blog and its opportunities. Altogether, International visitors from more than 50 countries. This having started the blog initiative, the first Immunology platform presents new scientific findings, “blog year” was a very enriching year for Training information on which research topics oth- me. I have enjoyed being part of a moti- er students are working on, how to accel- vated team with the aspiration of realizing Program Bonn erate your career or which workshops or the great potential of the Cluster’s young (IITB) courses to take. The Blog answers these investigator network to form a lively com- questions in categories like “How was...”, munity. The team has built up an online “Meet the Expert”, “Hard Science”, platform and has created a set of articles “Events” and “Short Profiles” within about on diverse topics. With the ImmunoSen- 50 articles to date, with more coming sation Blog I have discovered a lot about out every week. There has been great the fascinating diversity the ImmunoSen- interest in contributions to the “Meet the sation Cluster of Excellence offers and to- Expert” category with articles reporting on gether with my team I am enthusiastically Prof. Joachim L. Schultze how to promote your scientific career as looking forward to the future development well as “Hard Science” articles featuring of our blog! research topics from the Cluster of Ex-

82 83 Family Support & Gender Equality Cluster member Dr. Heine received the Lisec-Artz award for outstanding cancer Support for Scientists on Parental research in 2015. For more information Leave about Dr. Abdullah and Dr. Heine, please read the interviews on pages 51 and 53 In 2015 we supported two female sci- Our Goals for 2015 respectively. entists, Dr. Julia Vorac and Dr. Verena Schütte from the LIMES-Institute during In the 2014 ImmunoSensation Annual Re- means an increase of female scientists in MeTra: Support for Career Develop- their pregnancies and parental leave by port, we referred to a “leaking pipeline“, both groups. ment providing student assistants. a metaphor for the discrepancy between Although the number of female scientists Julia Vorac: “During my pregnancy a the number of talented women entering drops, as expected, at the professorial In order to offer female scientists long- student assistant was working in our the life-science field and those who later level to 13% (E), ImmunoSensation con- term career support, ImmunoSensation working group 12 hours a week, for 9 on assume senior leadership positions. siders positive that the number did not is participating in the networking program months in total, beginning in the fourth Stopping this leak remains a major priority drop under the 12% from 2013. At the (MeTra) for young women in academia month of my pregnancy. Being pregnant for ImmunoSensation. Cluster member level the percentage of organized by Dr. Martina Pottek from the meant that I was no longer allowed to women has declined from 20% in 2013 University of Bonn. perform particular experiments, such as ImmunoSensation in Numbers to 16% (A) in 2015. In order to counteract Two female scientists from Immuno- those involving carcinogenic chemicals. Family Support & this trend, promote female representation Sensation took part in the program in Thus, it was very important for me to get Gender Equality In 2015, the number of Cluster-associat- and reward their hard work, ImmunoSen- 2015, one from the group of Dr. Dagmar someone as soon as possible who was ed scientists increased once again. Within sation’s Steering Committee appointed Wachten (caesar) and the other from the able to take over these parts of my ex- this group we have the same percentage two excellent female scientists to Junior group of Prof. Dr. Volkmar Gieselmann. periments. With the help of Prof. Förster of female to male scientists (B). There are Research Group Leaders within Immuno- ImmunoSensation has already registered and Dr. Astrid Draffehn, we could hire a 56% (C) female scientists at the PhD level Sensation. another two young researchers for 2016, student assistant to help. It was definitely and 56% (D) at the PostDoc level, which and we are looking forward to continuing great to get this help already during my our cooperation with the University of pregnancy and not have to wait until my Bonn. maternity leave. This gave my student Family Support & assistant the opportunity to learn about Annual Network Meeting of the Clus- the experiments while I was still there, so Gender Equality ters of Excellence: Gender Equality that she could independently complete experiments during my maternity leave. The annual network meetings within the Also, the flexibility of choosing the best Clusters of Excellence are always a first- time period for the employment of the rate opportunity to exchange information student is ideal. However, in my opinion and expertise. The goal of these meetings some points might need some improve- is to raise awareness of the meaning of ment. Because of the administrative gender equality questions. The Clusters requirements at the university, there was agree that family-friendly science is a key a certain lag period before the student factor to successful science. In August could start working. Furthermore, the 2015 ImmunoSensation hosted the meet- information about what kind of financial Distribution of male and female researchers 2013 Distribution of male and female researchers 2015 ing in Bonn and we are looking forward to options are actually available for preg- more fruitful meetings. nant women should be more accessible. Appointment of Two Independent Fe- Some colleagues and supervisors are not male Junior Research Group Leaders Family-friendly Science even aware of the fact that financial resources, specifically for pregnant women Dr. Zeinab Abdullah (right) from the Insti- ImmunoSensation is aware that we have and young parents, are available.“ tute of Experimental Immunology (IEI) and a long way to go until we reach 100% Verena Schütte: “During my parental Dr. Annkristin Heine (left) from the Institute family-friendly science, but we are very leave, I was fortunate to have access of Experimental Immunology (IEI) & the pleased about the participation we have to a student assistant (SHK), who was Medical Clinic III have become Junior had in our programs in the last three financed by ImmunoSensation. For my Research Group Leaders within Immuno- years and the feedback we have re- research, this was a great support since Sensation. ceived. An overview of our programs is it kept my practical work in the lab from provided below.

84 85 Family Support & Gender Equality

Family Support & completely shutting down and after 6 Gender Equality months I could take over the running experiments. One reason why this worked so well is that we had a reliable student assistant who had performed his Bach- Angelika Griep, Dr. Beatrix Schumak and future scientists in the last year and will elor thesis in our lab and was already Stephanie Schwartz who made this day a continue to do so in the future. We have engaged in the project. The organization very special experience for the girls. One planned to continue our programs for and administration was done very quickly group at the IEI used pme during the Kita of this year’s participants even came back children in 2016 and will also include the and without any problems. I can strongly strike this year, and he was very happy to Prof. Heneka’s lab for an internship nursery “Max and Mary” (see above) in recommend and do appreciate this form with the service, because it was very con- during her summer school holidays. Nora our children’s program. of support. Thanks ImmunoSensation!” venient and easy to use, and the children Korber from the Liebfrauenschule Gym- ImmunoSensation is aware that these We are glad that this measure provides were happy with it - which is the most im- nasium in Cologne said: “After spending measures/activities are only small steps, rapid help and is now widely accepted al- portant thing. In 2015, ImmunoSensation my Girls’ Day at ImmunoSensation, I’m but as you can see we cast our net wide, though there is potential for improvement. has continued its cooperation with “Max even more sure that I want to be a scien- very wide and we hope to thereby en- Family Support & In particular, we are taking measures to and Mary”, the English-speaking nursery, tist one day, too. I’m interested in study- hance chances for the scientific world. Gender Equality make sure that female scientists are bet- which is located at the Venusberg. The ing chemistry after finishing school.” All in ter informed of the resources available to long opening hours and the flexible regis- all, we hope that we have inspired a few them. tration (no fixed deadlines as opposed to public childcare facilities) are key benefits Childcare Tailored to the Needs of Sci- for our scientists, especially for those entists who come from abroad. To encourage even the youngest of future scientists, ImmunoSensation cooperates with the ImmunoSensation will visit Max and Mary “pme Familienservice”, which provides in 2016 for the “Day of Immunology”. We childcare for emergencies, such as the hope to awaken their interest in science public childcare (Kita) strike this year, and and inspire the next generation of immu- holiday care during school holidays. The nologists! holiday care programs are tailored to the children’s needs; the children are super- Children and the Future of Science

ImmunoSensation would like to share its enthusiasm for immunology with people of all ages and levels of knowledge. For the second time, the ImmunoSensa- tion Cluster of Excellence participated in “Girls’ Day”. Five 14 to 15 year-old girls visited the Cluster at the University Hospital Bonn. After a short overview of ImmunoSensation’s history of origins and vised in suitable age groups, and the the structure from Nicole Dahms, the girls childcare ratio is above-average. If there spent the rest of the day in the labs of is a meeting within Germany, it is even the Institute of Neurology and Institute of Participants of the Girls’ Day 2015 with Nicole Dahms (left) possible to bring your child along and Medical Microbiology, Immunology and by Johann Saba - UKom benefit from the local pme service since Parasitology (IMMIP) at the University there are pme offices all over Germa- Hospital Bonn. The Cluster would espe- ny. César Evaristo from Christian Kurts’ cially like to thank the female scientists

86 87 Women in Science Mini-Symposium March 31, LIMES Institute

By Prof. Irmgard Förster tive research centers SFB 704, SFB 645 and TRR 83 at the University of Bonn. Among other initiatives, the LIMES-WiS program aims to enhance the visibility of successful female scientists as role mod- LIMES els for career development. LIMES-WiS Life & Medical Sciences Institute is also linked with the gender equality IN Women SCIENCE program of the Excellence Cluster “Im- munoSensation”. The Mini-Symposium

MINI-SYMPOSIUM was organized by Irmgard Förster, Joa- EPIGENETICS AND CHROMATIN STRUCTURE chim Schultze and Waldemar Kolanus and focused on the topic of epigenetics INVITED SPEAKERS: to provide a state-of-the-art overview on Round Table Discussion UTA-MARIA BAUER, MARBURG MILENA G.. KIRILOVA , SOFIA recent achievements within this rapidly JACQUELINE M ERMOUD, M ARBURG KAREN REDDY, BALTIMORE expanding field of research. In particular, JUDITH ZAUGG, HEIDELBERG it highlighted the importance of chromatin organization and positioning of genetic polymorphisms identified in genome wide dents in biomedicine and the apparent ARCH

om M 31, 2015 . c i d BONN, GERMANY

.img k information within the nucleus for regula- association studies, in particular their underrepresentation of women in leading w w w tion of gene transcription. Karen Reddy appearance in non-coding regions of the academic positions, the discussants first -No pre-registration required- The program will be available from www.limes-institut-bonn.de from the John Hopkins School of Med- human genome. After lively discussions tried to identify the main reasons for this LIMES-WiS is proudly supported by For further information please contact: SFB 704 Irmgard Förster icine, Baltimore, provided a fascinating during the lunch break Jaqueline Mer- unbalance. Obviously the problem is not LIMES Institute Carl-Troll-Str. 31, D-53115 Bonn [email protected] introduction to the importance of the nu- moud (Institute of Molecular Biology and restricted to Germany but similarly occurs clear lamina underlying the inner nuclear Tumor Research (IMT), University of Mar- in many other countries around the world. membrane in chromosomal gene silenc- burg) addressed the necessity of de novo While the double challenge of raising On March 31, 2015, the Mini-Symposium ing using the example of the immuno- chromatin silencing and appropriate his- children and being a competitive scien- „Epigenetics and Chromatin Structure“ globulin heavy chain locus. Judith Zaugg, tone modifications during the process of tists certainly represents a major hurdle, took place at the LIMES Institute in the a bioinformatician from the European DNA replication. The influence of environ- the level of self-confidence appears to frame of the LIMES Women in Science Molecular Biology Laboratories (EMBL) mentally induced epigenetic modifications be different between male and female (WiS) program. This program is spon- in Heidelberg, presented her recent work on cellular ageing was then discussed by scientists, often preventing women from sored through the DFG-funded collabora- on the quantification of single nucleotide Milena Georgieva Kirilova from the Bul- entering leadership positions. With lively garian Academy of Science in Sofia. The participation of the audience, some key last presentation of the Symposium was measures were proposed to improve given by Uta-Maria Bauer, who is also gender equality in academic positions. working at the IMT, University of Marburg. Among others, these included the inclu- She introduced a different class of histone sion of childcare facilities for employees modifying enzymes, namely the family directly within bigger University institutions of protein arginine methyltransferases similar to that existing in the EMBL, Hei- (PRMTs). After the scientific program the delberg; equal participation of parents in invited speakers participated in an inspir- child raising; a higher proportion of tenure ing podium discussion on gender equality track positions; and early recruitment of together with Michael Hoch, the rector of female scientists into challenging profes- the University of Bonn, Margret Bülow, sional tasks and responsibilities to build a young postdoc at the LIMES Insti- up self-confidence. Clearly, increasing the tute, and Irmgard Förster as head of the visibility of successful female scientists in LIMES-WiS program. Facing the obvious meetings like this will help to encourage discrepancy between the high proportion women to further pursue a research ca- (60-70%) of female undergraduate stu- reer. Podium Discussion on gender equality

88 89 Public Relations

Immuna and Immuno visit the Villa Hammerschmidt Public We are proud that ImmunoSensation Relations could participate in the Open Day at the Villa Hammerschmidt on June 14, 2015 (11am-6 pm). The Open Day in the Vil- la Hammerschmidt is a family-friendly event that gives the public the opportunity to visit the official residence of the Federal President Joachim Gauck. The ”Chancellor’s Bungalow” and parts of the Federal Chancellery were also open to Public visitors then, as well. A diverse program for families was also offered at the event, Relations Open Day at Villa Hammerschmidt including contributions from caesar (center of advanced european studies and research), the Hausdorff Center for Math- ematics and ImmunoSensation. Immu- noSensation offered its “sensing game”, which was immensely popular at the “9th Night of Science” in 2014. Participants First Issue of ‘The Cluster TImes’ released December 2015 test their tactile senses in order to better understand how our immune system discriminates between harmful and harm- less, again. Immuna and Immuno were so busy explaining the immune system to the visitors that they did not have much of Childrens’ University a chance to see the Villa, but they prom- ‘Sensing Game’ ised to be back! In 2015, our programs for children included another beloved tradition: the participation in the “Kinderuni” (the Uni- versity of Bonn) for children aged 8 - 13. Social Media and Hompage This time Professor Eicke Latz presented ImmunoSensation to this young audience. His topic was “Das Abwehrsystem des Körpers: Die Polizei in Dir” (or “The 128 Follower immune system: your very own internal (2014: 90) police force”), with lively discussions between Professor Latz and the children. In 2016, the torch will be passed on to Dr. 1375 Visitors Annett Halle (caesar). For more informa- (2014: 1086) tion about Prof. Latz (see page 192) and 49 Follower Dr. Halle (see page 181), please see their (2014: 25) biosketches.

90 91 List of ImmunoSensation Seminars 2015

ImmunoSensation ImmunoSensation Seminar: Exosome and RNA secretion by helminths March 04, 2015 Dr. Amy Buck, The University of Edinburgh, Division of Infection and Pathway Medicine, Seminars, Seminars of UK ImmunoSensation Seminar: Regulation of myeloid cell development and host- pathogen interactions by the canonical miRNA pathway March 09, 2015 Cluster Cooperation Dr. Nikoletta Papadopoulou, Institute for Med. Microbiology, Immunology and Hygiene, University of Cologne, Germany

ImmunoSensation Seminar: Dynamics and function of the master transcriptional fac- Partners and tor Bcl6 in Follicular T helper cells March 16, 2015 Weiwei Ma, Group of Prof. Hai Qi, Tsinghua University, Beijing, China Meetings ImmunoSensation Seminar: New roles for immune components in immunity to helminths March 23, 2015 Dr. William Horsnell, Institute of Infectious Disease and Molecular Medicine & Dept. of Clinical Laboratory Sciences, University of Cape Town, South Africa

ImmunoSensation Seminar: Regulatory T cells, IL-2 and type-1-diabetes April 20, 2015 Dr. Emma Hamilton-Williams, Translational Research Institute, Diamantina Institute, The University of Queensland, Australia

ImmunoSensation Seminar: Dynamic regulation of permissive histone modifications and GATA3 underpin acquisition of Granzyme A in CD8+ T cells April 24, 2015 Michelle Nguyen, Department of Microbiology & Immunology, The Peter Doherty Insti- tute for Infection and Immunity, The University of Melbourne, Australia

ImmunoSensation Seminar: Induction of regulatory B cells by schistosome egg antigens May 12, 2015 Dr. Simone Häberlein, Department of Parasitology, Leiden University Medical Center, Netherlands

ImmunoSensation Seminar: A surprising connection: Invariant T cells, vitamins, bacteria and wild mice June 30, 2015 Prof. Olivier Lantz, Immunité et Cancer, Institut Curie Paris, France

93 ImmunoSensation Seminars 2015 ImmunoSensation Seminars 2015

ImmunoSensation Seminar: The parasitic worm product ES-62: a starting point for ImmunoSensation Seminar: What turns Aire on? Transcriptional programs novel anti-inflammatory drug development controlling the expression of the Autoimmune Regulator gene August 25, 2015 December 03, 2015 Prof. William Harnett, Strathclyde Institute of Pharmacy and Biomedical Sciences, Uni- Yonatan Herzig, Jakub Abramson’s lab, Weizmann Institute of Science, Israel versity of Strathclyde, Scotland ImmunoSensation Seminar: The Cholinergic signaling impairment in neuro ImmunoSensation Seminar: Elastases and related serine proteases of neutrophils: inflammatory syndromes intensifiers of defense and destruction December 09, 2015 September 22, 2015 Dr. Shani Shenhar-Tsarfaty, The Edmond and Lily Safra Center for Brain Sciences, The Dr. Dieter Jenne, Institute of Lung Biology and Disease (iLBD), Comprehensive Hebrew University of Jerusalem, Israel Pneumology Center (CPC), Helmholtz Zentrum München, Germany ImmunoSensation Seminar: CholinomiRs: From anxiety and inflammation to ImmunoSensation Seminar & Meet-the-expert: Controlling the Input and Output of humanized Cholinergic regulation in mice Germinal Centers: Roles for Myb and PRMT1 December 09, 2015 October 5, 2015 Bettina Nadorp, The Edmond and Lily Safra Center for Brain Sciences, The Hebrew Prof. David Tarlinton, Walter and Eliza Hall Institute of Medical Research, Melbourne, University of Jerusalem, Israel Australia

ImmunoSensation Seminar: From mice to men: MicroRNA regulators of stress- induced cholinergic signaling October 6, 2015 Seminars Cooperation Partners 2015 Prof. Hermona Soreq, The Edmond and Lily Safra Center for Brain Sciences, The He- brew University of Jerusalem, Israel

ImmunoSensation Seminar: RIG-I like receptors and autoimmune diseases October 9, 2015 Bonn Lecture Series in Neuroscience: Astrocytic and neuronal large-pore (hemi) Prof. Hiroki Kato, Institute for Virus Research, Kyoto University, Japan channels: Activation and permeability January 13, 2015 ImmunoSensation Technical Seminar: Deutsches Schutz-/ Patentrecht Nanna MacAulay, Ph.D. Associate Professor, Institute of Cellular and Molecular October 22, 2015 Medicine, University of Copenhagen, Denmark Rüdiger Mull, Rheinische Friedrich-Wilhems-Universität Bonn, Germany SFB 704 Seminar: Therapeutic T cell vaccination through antigen targeting into cross- ImmunoSensation Seminar: Rhythmic control of leukocyte migration presenting dendritic cells November 24, 2015 January 20, 2015 Dr. Christoph Scheiermann, Walter-Brendel-Zentrum für Experimentelle Medizin, Lud- Prof. Richard Kroczek, Molekulare Immunologie, Robert Koch-Institut, Berlin, Germany wig-Maximilian-Universität München, Germany Bonn Lecture Series in Neuroscience: Functional organisation of connection strength ImmunoSensation Seminar & Meet-the-expert: Inducing monocyte function during in neocortical circuits acute gastrointestinal infection January 29, 2015 December 01, 2015 Prof. Dr. Thomas Mrsic-Flogel, Associate Professor in Neuroscience, Biocenter, Dr. John Grainger, Manchester Collaborative Centre for Inflammation Research (MC- University of Basel, Switzerland CIR), Inflammatory cell function and conditioning during infection, The University of Manchester, England Bonn Lecture Series in Neuroscience: Plasticity of hippocampal mossy fiber synapses February 19, 2015 Prof. Dr. Dr. Michael Frotscher, Center for Molecular Neurobiology, Institute for Structural Neurobiology, University Medical Center Hamburg-Eppendorf, Germany

94 95 Seminars Cooperation Partners 2015 Seminars Cooperation Partners 2015

Women in Science Seminar Series: Prof. Dr. Rüdiger Klein, Director, Max-Planck-Institute of Neurobiology, Department of Mini Symposium: Epigenetics and Chromatic Structure, see page 88 Molecular Neurobiology, München-Martinsried, Germany March 31, 2015 LIMES Institute, Bonn, Germany Bonn Lecture Series in Neuroscience: Synapses and Dementia? June 22, 2015 Women in Science Seminar Series: Prof. Dr. Dietmar Schmitz, Deutsches Zentrum für Neurodegenerative Erkrankungen Exploring the Molecular Signature of Mammalian Touch and Pain- Insights into Health (DZNE), Charité - Universitätsmedizin Berlin, Germany and Disease April 20, 2015 Bonn Lecture Series in Neuroscience: GABAergic action and the activity-dependent Dr. Manuela Schmidt, Somatosensory Signaling, Max Planck Institute of Experimental dendritic inhibition in the primary gate of hippocampus Medicine, Göttingen, Germany June 23, 2015 Dr.Yu-Chao Liu, Institute of Neuroscience, National Yang-Ming University, Taipei 112, Bonn Lecture Series in Neuroscience: Degradation of Tau Protein by Selective Taiwan, China Autophagy May 11, 2015 Bonn Lecture Series in Neuroscience: Towards understanding positive symptoms of Gail V. Johnson, University of Rochester Medical Center, N.Y., USA DiGeorge syndrome and schizophrenia July 03, 2015 Bonn Lecture Series in Neuroscience: Bridging the scales: Spiking networks for Dr. Stanislav S. Zakharenko, Developmental Neurobiology St. Jude Children’s biological and artificial neural computation Research Hospital Memphis, USA May 15, 2015 Dr. Raoul-Martin, Memmesheimer Department for Neuroinformatics, Donders Center, Bonn Lecture Series in Neuroscience: Microtubules during nervous system Radboud University Nijmegen, Netherlands development and disease July 16, 2015 Bonn Lecture Series in Neuroscience: Synaptic tenacity: When everything changes, Peter W. Baas, Dept. Neuroscience, Drexel University, Philadelphia, PA, USA do things really stay the same? May 18, 2015 Bonn Lecture Series in Neuroscience: Deconstructing complexity through spectral Prof. Dr. Noam E. Ziv, Technion, Dept. of Physiology, Rappaport Faculty of Medicine imaging and metagenomics: Systems analysis of the oral microbiome and Network Biology Research Laboratorie, Haifa, Israel July 23, 2015 Gary G. Borisy, Dept. Microbiology, Forsyth Institute Cambridge, MA, USA SFB 704 Seminar: Transcutaneous Immunization – Regulation of local inflammatory responses to generate systemic tumor immunity Bonn Lecture Series in Neuroscience: Physiology and functional effects of tDCS and May 19, 2015 related techniques PD Dr. Markus P. Radsak, III. Medizinische Klinik, Universität Mainz, Germany July 28, 2015 Prof. Dr. Michael A. Nitsche, Dept. Clinical Neurophysiology, University Medicine Bonn Lecture Series in Neuroscience: Fluorescence Trails Microscopy: A Multifocal Göttingen Imaging Technique for Fast Optical Recordings of Neuronal Activity June 12, 2015 Bonn Lecture Series in Neuroscience: Medical Text Analytics for Neurodegenerative Matthew Shtrahman, Departments of Neurology and Neurobiology, UCLA David Geffen Diseases School of Medicine, USA August 12, 2015 Daniel Damian, Centre Leenaards de la Memoire - CHUV, University Hospital of Bonn Lecture Series in Neuroscience: Netrin-ephrin synergy in motor axon guidance Lausanne, Switzerland June 17, 2015 Artur Kania, PhD, Director, Neural Circuit Development Laboratory, Institut de Bonn Lecture Series in Neuroscience: Recent progress toward a high-performance recherches cliniques de Montréal (IRCM), Montréal, Canada neural prosthesis September 16, 2015 Bonn Lecture Series in Neuroscience: The molecular logic of axon guidance Prof. Dr. Andrew Schwartz, Department of Neurobiology, University of Pittsburgh, USA June 22, 2015

96 97 Seminars Cooperation Partners 2015 Seminars Cooperation Partners 2015

Bonn Lecture Series in Neuroscience: Functional imaging hippocampal microcircuits October 28, 2015 for spatial navigation and learning Dr. Sophie Tezenas du Montcel, Department of Biostatistics and Medical Informatics, September 24, 2015 Paris, France Attila Losonczy, Department of Neuroscience, Mortimer B. Zuckerman Mind Brain Behavior Institute, Kavli Institute for Brain Science, Columbia University, USA SFB 704 Seminar: Physiologic and immunopathologic features of single cells and whole organs revealed by 2-Photon and lightsheet microscopy Bonn Lecture Series in Neuroscience: The Cell Biology and Biochemistry of November 11, 2015 Microtubule Nucleation Prof. Matthias Gunzer, Institut für Experimentelle Immunologie und Bildgebung, September 28, 2015 Universität Duisburg-Essen, Germany Prof. Dr. Gary Brouhard, Department of Biology, McGill University, Montréal, Quebec, Canada Bonn Lecture Series in Neuroscience: Serum protein biomarkers of the latent dementia variable d(delta) SFB 704 Seminar: Myeloid cells, T cells and Legionella infection in the lung November 11, 2015 October 06, 2015 Donald R. Royall, Department of Psychiatry, The University of Texas Health Science Prof. Ian van Driel, Department of Biochemistry and Molecular Biology, University of Center, San Antonio, TX, USA Melbourne, Australia Bonn Lecture Series in Neuroscience: Astrocytic contribution to synaptic Bonn Lecture Series in Neuroscience: Chaperone- and Translocon-modulated transmission Folding Pathways of Single Membrane Proteins November 19, 2015 October 09, 2015 Prof. Stéphane H. Oliet, Neurocentre Magendie, University of Bordeaux, Bordeaux, Daniel Müller, Dept. Biosystems Science and Engineering, ETH-Zürich, Basel, France Switzerland Bonn Lecture Series in Neuroscience: Ionenkanalmodulation in der Multiplen Bonn Lecture Series in Neuroscience: Bi-directional control of epileptic networks by Sklerose – Fakten und Phantasien the thalamus December 01, 2015 October 15, 2015 Prof. Dr. Sven Meuth, Klinik für Neurologie, Universität Münster, Germany Prof. Jeanne T. Paz, Gladstone Institute of Neurological Disease & Neurology at UCSF, San Francisco, USA Bonn Lecture Series in Neuroscience: An ion channel which regulates immune surveillance of the brain by microglia Bonn Lecture Series in Neuroscience: The potential role of microglia in December 10, 2015 neuroprotection and depression Dr. Christian Madry, Department of Neuroscience, Physiology and Pharmacology, UK October 23, 2015 Prof. Dr. Knut Biber, Department of Psychiatry and Psychotherapy, University Hospital Freiburg, Germany

Bonn Lecture Series in Neuroscience: Building Memories: Sparse Coding and Learning of Associations by Single Neurons in the Human Brain October 26, 2015 Matias J Ison, University of Leicester, UK

Bonn Lecture Series in Neuroscience: Sensor-basierte Bewegungsanalyse beim Parkinson Syndrom October 27, 2015 Dr. Jochen Klucken, Hospital for Neurology, University Erlangen, Germany

Bonn Lecture Series in Neuroscience: Joint longitudinal and survival analysis. Application to the Spinocerebellar Ataxia data

98 99 Meetings 2015

7th International Symposium on DAMPs and HMGB1 September 10 - 12, 2015 University Hospital Bonn and Wasserwerk Bonn, Germany

3rd Cluster Science Days 2015 November 02 & 03, 2015 University Hospital Bonn, Germany

Impressions Cluster Science Days 2015 Impressions Cluster Science Days 2015

100 101 Publications ImmunoSensation Publication List 2015

Al Haj A, Mazur AJ, Radaszkiewicz Østergaard L, Ørntoft TF, Hornung K, Radaszkiewicz T, Makowiecka V, Paludan SR, Mikkelsen JG, A, Stopschinski BE, Schönichen A, Fujita T, Christiansen M, Hartmann Geyer M, Mannherz HG. Distribution R, Mogensen TH. Functional IRF3 of formins in cardiac muscle: FHOD1 deficiency in a patient with herpes is a component of intercalated discs simplex encephalitis. J. Exp. Med. and costameres. Eur. J. Cell Biol. 2015 Aug 24;212(9): 1371-1379 2015 Feb 1;94(2): 101-113 Anggakusuma , Frentzen A, Gürlevik Al-Gethamy M, Corman VM, Hussain E, Yuan Q, Steinmann E, Ott M, R, Al-Tawfiq JA, Drosten C, Memish Staeheli P, Hornung V, Kuehnel ZA. A case of long-term excretion F, Pietschmann T. Control of HCV and subclinical infection with MERS- replication in mouse liver derived cells Coronavirus in a health care worker. by MAVS-dependent production of Clin. Infect. Dis. 2015 Mar 15;60(6): type-I and -III interferons. J. Virol. 973-974 2015 Apr 1;89(7): 3833-3845

Allam JP, Haidl G, Novak N. [Semen Annan A, Ebach F, Corman VM, allergy]. Hautarzt 2015 Dec 1;66(12): Krumkamp R, Adu-Sarkodie Y, Eis- 919-923 Hübinger AM, Kruppa T, Simon A, May J, Evans J, Panning M, Drosten Ammann RA, Laws HJ, Schrey D, C, Drexler JF. Similar virus spectra Ehlert K, Moser O, Dilloo D, Bode and seasonality in paediatric patients U, Wawer A, Schrauder A, Cario G, with acute respiratory disease, Ghana Laengler A, Graf N, Furtwängler R, and Germany. Clin. Microbiol. Infect. Simon A. Bloodstream infection in 2015 Nov 14 paediatric cancer centres-leukaemia and relapsed malignancies are Annan A, Owusu M, Marfo KS, Larbi independent risk factors. Eur. J. R, Sarpong FN, Adu-Sarkodie Y, Pediatr. 2015 May 1;174(5): 675-686 Amankwa J, Fiafemetsi S, Drosten C, Owusu-Dabo E, Eckerle I. High Anadol E, Schierwagen R, Elfimova N, prevalence of common respiratory Tack K, Schwarze-Zander C, Eischeid viruses and no evidence of Middle H, Noetel A, Boesecke C, Jansen C, East Respiratory Syndrome Dold L, Wasmuth JC, Strassburg CP, Coronavirus in Hajj pilgrims returning Spengler U, Rockstroh JK, Odenthal to Ghana, 2013. Trop. Med. Int. M, Trebicka J. Circulating miRNAs as Health 2015 Jun 1;20(6): 807-812 marker for liver injury in HIV patients. Hepatology 2015 Jan 1;61(1): 46-55 Anti P, Owusu M, Agbenyega O, Annan A, Badu EK, Nkrumah EE, Andersen LL, Mørk N, Reinert LS, Tschapka M, Oppong S, Adu- Kofod-Olsen E, Narita R, Jørgensen Sarkodie Y, Drosten C. Human-Bat SE, Skipper KA, Höning K, Gad HH, Interactions in Rural West Africa.

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Emerging Infect. Dis. 2015 Aug C, Chertkoff R, Alon S, Shaikevich Banerjee S, Resch Y, Chen KW, Basmanav FB, Forstner AJ, Fier 1;21(8): 1418-1421 D, Volokhov I, Haim KY, Bartfeld D, Swoboda I, Focke-Tejkl M, Blatt H, Herms S, Meier S, Degenhardt Shulman A, Ruderfer I, Ben-Moshe K, Novak N, van Hage M, Ferrara F, Hoffmann P, Barth S, Fricker N, Anz D, Rapp M, Eiber S, Koelzer T, Shilovitzky O, Soreq H, Shaaltiel R, Mari A, Purohit A, Pauli G, Strohmaier J, Witt SH, Ludwig M, VH, Thaler R, Haubner S, Knott Y. Preclinical and first-in-human Sibanda EN, Ndlovu P, Thomas WR, Schmael C, Moebus S, Maier W, M, Nagel S, Golic M, Wiedemann evaluation of PRX-105, a PEGylated, Krzyzanek V, Tacke S, Malkus U, Mössner R, Rujescu D, Rietschel GM, Bauernfeind F, Wurzenberger plant-derived, recombinant human Valent P, Valenta R, Vrtala S. Der M, Lange C, Nöthen MM, Cichon C, Hornung V, Scholz C, Mayr D, acetylcholinesterase-R. Toxicol. p 11 is a Major Allergen for House S. Investigation of the role of Rothenfusser S, Endres S, Bourquin Appl. Pharmacol. 2015 Sep Dust Mite Allergic Patients Suffering TCF4 rare sequence variants in C. Suppression of intratumoral CCL22 15;287(3): 202-209 from Atopic Dermatitis. J. Invest. schizophrenia. Am. J. Med. Genet. by type i interferon inhibits migration of Dermatol. 2015 Jan 1;135(1): 102- B Neuropsychiatr. Genet. 2015 Jul regulatory T cells and blocks cancer Aung T, Ozaki M, Mizoguchi T, 109 1;168B(5): 354-362 progression. Cancer Res. 2015 Nov Allingham RR, [...] Nöthen MM, [...] 1;75(21): 4483-4493 Sundaresan P, John SW, Ritch R, Barchet W, Zillinger T. Exonuclease Basmanav FB, Fritz G, Lestringant Hauser MA, Khor CC. A common TREX1 also Has a Sweet Tooth. GG, Pachat D, Hoffjan S, Fischer Arndts K, Klarmann-Schulz U, Batsa variant mapping to CACNA1A is Immunity 2015 Sep 15;43(3): 411- J, Wehner M, Wolf S, Thiele H, L, Debrah AY, Epp C, Fimmers R, associated with susceptibility to 413 Altmüller J, Pulimood SA, Rütten Specht S, Layland LE, Hoerauf A. exfoliation syndrome. Nat. Genet. A, Kruse R, Hanneken S, Frank Reductions in microfilaridermia by 2015 Apr 1;47(4): 387-392 Barrangou R, Birmingham A, J, Danda S, Bygum A, Betz RC. repeated ivermectin treatment are Wiemann S, Beijersbergen RL, Pathogenicity of POFUT1 in Dowling- associated with lower Plasmodium- Ayub TH, Keyver-Paik MD, Debald M, Hornung V, Smith AV. Advances in Degos Disease: Additional Mutations specific Th17 immune responses Rostamzadeh B, Thiesler T, Schröder CRISPR-Cas9 genome engineering: and Clinical Overlap with Reticulate in Onchocerca volvulus-infected L, Barchet W, Abramian A, Kaiser lessons learned from RNA Acropigmentation of Kitamura. J. individuals. Parasit Vectors 2015 Jan C, Kristiansen G, Kuhn W, Kübler interference. Nucleic Acids Res. Invest. Dermatol. 2015 Feb 1;135(2): 1;8(): 184 K. Accumulation of ALDH1-positive 2015 Apr 20;43(7): 3407-3419 615-618 cells after neoadjuvant chemotherapy Aslanidis A, Karlstetter M, Scholz predicts treatment resistance and Bartesaghi S, Graziano V, Galavotti S, Bauer JS, Ghequire MG, Nett M, R, Fauser S, Neumann H, Fried prognosticates poor outcome in Henriquez NV, Betts J, Saxena J, A D, Josten M, Sahl HG, De Mot R, C, Pietsch M, Langmann T. ovarian cancer. Oncotarget 2015 Jun Karlsson A, Martins LM, Capasso M, Gross H. Biosynthetic Origin of the Activated microglia/macrophage 30;6(18): 16437-16448 Nicotera P, Brandner S, De Laurenzi Antibiotic Pseudopyronines A and B whey acidic protein (AMWAP) V, Salomoni P. Inhibition of oxidative in Pseudomonas putida BW11M1. inhibits NF B signaling and induces Bach JP, Gold M, Mengel D, metabolism leads to p53 genetic Chembiochem 2015 Nov 1;16(17): a neuroprotective phenotype in Hattesohl A, Lubbe D, Schmid S, inactivation and transformation in 2491-2497 microglia. Jκ Neuroinflammation 2015 Tackenberg B, Rieke J, Maddula neural stem cells. Proc. Natl. Acad. Jan 1;12(): 77 S, Baumbach JI, Nell C, Boeselt T, Sci. U.S.A. 2015 Jan 27;112(4): Baurecht H, Hotze M, Brand S, Michelis J, Alferink J, Heneka M, 1059-1064 Büning C, Cormican P, [...] Nöthen Ativie F, Albayram O, Bach K, Oertel W, Jessen F, Janciauskiene S, MM, Novak N,[...], Barker J, Elder JT, Pradier B, Zimmer A, Bilkei-Gorzo Vogelmeier C, Dodel R, Koczulla AR. Basi-Chipalu S, Dischinger J, Josten Weidinger S, Cordell HJ, Brown SJ. A. Enhanced microglial activity in Measuring Compounds in Exhaled M, Szekat C, Zweynert A, Sahl HG, Genome-wide Comparative Analysis FAAH(-/-) animals. Life Sci. 2015 Oct Air to Detect Alzheimer‘s Disease Bierbaum G. Pseudomycoicidin, of Atopic Dermatitis and Psoriasis 1;138(): 52-56 and Parkinson‘s Disease. PLoS ONE a class II lantibiotic from Bacillus. Gives Insight into Opposing Genetic 2015 Jan 1;10(7): e0132227 Appl. Environ. Microbiol. 2015 May Mechanisms. Am. J. Hum. Genet. Atsmon J, Brill-Almon E, Nadri-Shay 15;81(10): 3419-3429 2015 Jan 8;96(1): 104-120

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AM. Genome-wide meta-analysis Brossart P, Flaherty P, Feldmann G. Abdullah Z, Sander J, Höchst B, Becker J, May A, Gerges C, Anders in alopecia areata resolves HLA Cyclin-Dependent Kinase 5 (CDK5) Eickhoff S, Rieckmann JC, Russo M, Veits L, [...] Nöthen MM, [...] associations and reveals two new Controls Melanoma Cell Motility, C, Bauer T, Flecken T, Giesen D, Neuhaus H, Rösch T, Ell C, Gockel I, susceptibility loci. Nat Commun 2015 Invasiveness, and Metastatic Spread- Engel D, Jung S, Busch DH, Protzer Schumacher J. Supportive evidence Jan 1;6(): 5966 Identification of a Promising Novel U, Thimme R, Mann M, Kurts C, for FOXP1, BARX1, and FOXF1 as therapeutic target. Transl Oncol 2015 Schultze JL, Kastenmüller W, genetic risk loci for the development Bevans CG, Krettler C, Reinhart C, Aug 1;8(4): 295-307 Knolle PA. Functional classification of of esophageal adenocarcinoma. Watzka M, Oldenburg J. Phylogeny memory CD8(+) T cells by CX3CR1 Cancer Med 2015 Nov 1;4(11): of the Vitamin K 2,3-Epoxide Björkqvist J, de Maat S, expression. Nat Commun 2015 Jan 1700-1704 Reductase (VKOR) Family and Lewandrowski U, Di Gennaro A, 1;6(): 8306 Evolutionary Relationship to the Oschatz C, Schönig K, Nöthen Bernhardt M, Pflugrad H, Goldbecker Disulfide Bond Formation Protein B MM, Drouet C, Braley H, Nolte MW, Boutaffala L, Bertrand MJ, A, Barg-Hock H, Knitsch W, (DsbB) Family. Nutrients 2015 Aug Sickmann A, Panousis C, Maas C, Remouchamps C, Seleznik G, Klempnauer J, Strassburg 1;7(8): 6224-6249 Renné T. Defective glycosylation Reisinger F, Janas M, Bénézech CP, Hecker H, Weissenborn of coagulation factor XII underlies C, Fernandes MT, Marchetti S, K, Tryc AB. Central Nervous Bieber T, Straeter B. Off-label hereditary angioedema type III. J. Mair F, Ganeff C, Hupalowska A, System Complications After Liver prescriptions for atopic dermatitis in Clin. Invest. 2015 Aug 3;125(8): Ricci JE, Becher B, Piette J, Knolle Transplantation: Common but Mostly Europe. Allergy 2015 Jan 1;70(1): 3132-3146 P, Caamano J, Vandenabeele Transient Phenomena. Liver Transpl. 6-11 P, Heikenwalder M, Dejardin E. 2015 Feb 1;21(2): 224-232 Blohberger J, Kunz L, Einwang D, NIK promotes tissue destruction Biermann J, Horack M, Kahlert P, Berg U, Berg D, Ojeda SR, Dissen independently of the alternative NF- Berres ML, Asmacher S, Lehmann Schneider S, Nickenig G, Zahn GA, Fröhlich T, Arnold GJ, Soreq H, B pathway through TNFR1/RIP1- J, Jansen C, Görtzen J, Klein S, R, Senges J, Erbel R, Wasem Lara H, Mayerhofer A. Readthrough induced apoptosis. Cell Death Differ. Meyer C, Strunk HM, Fimmers R, J, Neumann T. The impact of acetylcholinesterase (AChE-R) and 2015κ Dec 1;22(12): 2020-2033 Tacke F, Strassburg CP, Trautwein transcatheter aortic valve implantation regulated necrosis: pharmacological C, Sauerbruch T, Wasmuth HE, on quality of life: results from the targets for the regulation of ovarian Branchi V, Lingohr P, Willinek Trebicka J. CXCL9 is a prognostic German transcatheter aortic valve functions? Cell Death Dis 2015 Jan WA, Bölke E, Semaan A, Zhou H, marker in patients with liver cirrhosis interventions registry. Clin Res 1;6(): e1685 Kristiansen G, Klöppel G, Kalff JC, receiving transjugular intrahepatic Cardiol 2015 Oct 1;104(10): 877-886 Schäfer N, Matthaei H. Extensive portosystemic shunt. J. Hepatol. Börger C, Schünke S, Lecher J, Stoldt multifocal branch duct IPMN of the 2015 Feb 1;62(2): 332-339 Binger T, Annan A, Drexler JF, Müller M, Winkhaus F, Kaupp UB, Willbold pancreas after liver transplantation: is MA, Kallies R, Adankwah E, Wollny R, D. Resonance assignment of the surgery justified? Eur. J. Med. Res. Betz RC, Petukhova L, Ripke S, Kopp A, Heidemann H, Dei D, Agya- ligand-free cyclic nucleotide-binding 2015 Jan 1;20(): 26 Huang H, Menelaou A, Redler S, Yao FC, Junglen S, Feldt T, Kurth A, domain from the murine ion channel Becker T, Heilmann S, Yamany T, Oppong S, Adu-Sarkodie Y, Drosten HCN2. Biomol NMR Assign 2015 Brandstetter C, Mohr LK, Latz E, Holz Duvic M, Hordinsky M, Norris D, C. A novel rhabdovirus isolated from Oct 1;9(2): 243-246 FG, Krohne TU. Light induces NLRP3 Price VH, Mackay-Wiggan J, de the straw-coloured fruit bat Eidolon inflammasome activation in retinal Jong A, DeStefano GM, Moebus S, helvum with signs of antibodies in Böttcher J, Knolle PA. Global pigment epithelial cells via lipofuscin- Böhm M, Blume-Peytavi U, Wolff H, swine and humans. J. Virol. 2015 Apr transcriptional characterization mediated photooxidative damage. J. Lutz G, Kruse R, Bian L, Amos CI, 1;89(8): 4588-4597 of CD8(+) T cell memory. Semin. Mol. Med. 2015 Aug 1;93(8): 905- Lee A, Gregersen PK, Blaumeiser Immunol. 2015 Feb 1;27(1): 4-9 916 B, Altshuler D, Clynes R, de Bakker Bisht S, Nolting J, Schütte U, PI, Nöthen MM, Daly MJ, Christiano Haarmann J, Jain P, Shah D, Böttcher JP, Beyer M, Meissner F, Broderick L, De Nardo D, Franklin

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BS, Hoffman HM, Latz E. The and Lactation Despite Chronic Challagundla M, Koch JC, Ribas biomarker evaluation study to guide Inflammasome and Autoinflammatory Intestinal Failure Requiring Home VT, Michel U, Kügler S, Ostendorf T, the development of novel type I Syndromes. Annu Rev Pathol 2015 Parenteral Nutrition. Nutr Clin Pract Bradke F, Müller HW, Bähr M, Lingor interferon- based therapies. BMC Jan 1;10(): 395-424 2015 Dec 1;30(6): 807-814 P. AAV-mediated expression of BAG1 Pharmacol Toxicol 2015 Jan 1;16(1): and ROCK2-shRNA promote neuronal 25 Bruegmann T, van Bremen T, Vogt Buerfent BC, Gondorf F, Wohlleber D, survival and axonal sprouting in a rat CC, Send T, Fleischmann BK, Sasse Schumak B, Hoerauf A, Hübner MP. model of rubrospinal tract injury. J. Coles CH, Bradke F. Coordinating P. Optogenetic control of contractile E. coli-induced immune paralysis is Neurochem. 2015 Jul 1;134(2): 261- Neuronal Actin-Microtubule Dynamics. function in skeletal muscle. Nat not exacerbated during chronic filarial 275 Curr. Biol. 2015 Aug 3;25(15): Commun 2015 Jan 1;6(): 7153 infection. Immunology 2015 May R677-R691 1;145(1): 150-160 Chessa F, Mathow D, Wang Brüll V, Burak C, Stoffel-Wagner B, S, Hielscher T, Atzberger A, Coll RC, Robertson AA, Chae JJ, Wolffram S, Nickenig G, Müller C, Cabanillas B, Cuadrado C, Rodriguez Porubsky S, Gretz N, Burgdorf S, Higgins SC, Muñoz-Planillo R, Inserra Langguth P, Alteheld B, Fimmers R, J, Hart J, Burbano C, Crespo JF, Gröne HJ, Popovic ZV. The renal MC, Vetter I, Dungan LS, Monks Naaf S, Zimmermann BF, Stehle P, Novak N. Potential changes in the microenvironment modifies dendritic BG, Stutz A, Croker DE, Butler MS, Egert S. Effects of a quercetin-rich allergenicity of three forms of peanut cell phenotype. Kidney Int. 2015 Oct Haneklaus M, Sutton CE, Núñez G, onion skin extract on 24 h ambulatory after thermal processing. Food Chem 14 Latz E, Kastner DL, Mills KH, Masters blood pressure and endothelial 2015 Sep 15;183(): 18-25 SL, Schroder K, Cooper MA, O‘Neill function in overweight-to-obese Chiriac AI, Kloss F, Krämer J, Vuong LA. A small-molecule inhibitor of patients with (pre-)hypertension: a Cabanillas B, Novak N. Allergic C, Hertweck C, Sahl HG. Mode the NLRP3 inflammasome for the randomised double-blinded placebo- Reactions to Pine Nut: A Review. J of action of closthioamide: the first treatment of inflammatory diseases. controlled cross-over trial. Br. J. Nutr. Investig Allergol Clin Immunol 2015 member of the polythioamide class Nat. Med. 2015 Mar 1;21(3): 248-255 2015 Oct 28;114(8): 1263-1277 Jan 1;25(5): 329-333 of bacterial DNA gyrase inhibitors. J. Antimicrob. Chemother. 2015 Sep Cooper G, Lasser-Katz E, Simchovitz Brungs S, Kolanus W, Hemmersbach Carretero R, Sektioglu IM, Garbi 1;70(9): 2576-2588 A, Sharon R, Soreq H, Surmeier DJ, R. Syk phosphorylation-a N, Salgado OC, Beckhove P, Goldberg JA. Functional segregation gravisensitive step in macrophage Hämmerling GJ. Eosinophils Clarner T, Janssen K, Nellessen L, of voltage-activated calcium signalling. Cell Commun. Signal orchestrate cancer rejection by Stangel M, Skripuletz T, Krauspe B, channels in motoneurons of the 2015 Jan 1;13(): 9 normalizing tumor vessels and Hess FM, Denecke B, Beutner C, dorsal motor nucleus of the vagus. J. enhancing infiltration of CD8(+) T cells. Linnartz-Gerlach B, Neumann H, Neurophysiol. 2015 Sep 1;114(3): Buch S, Stickel F, Trépo E, Way Nat. Immunol. 2015 Jun 1;16(6): Vallières L, Amor S, Ohl K, Tenbrock 1513-1520 M, Herrmann A, [...] Nöthen MM, 609-617 K, Beyer C, Kipp M. CXCL10 Triggers [...] Hellerbrand C, Moreno C, Early Microglial Activation in the Corman VM, Baldwin HJ, Fumie Franchimont D, Morgan MY, Hampe Caspers M, Czogalla KJ, Liphardt K, Cuprizone Model. J. Immunol. 2015 Tateno A, Melim Zerbinati R, Annan J. A genome-wide association study Müller J, Westhofen P, Watzka M, Apr 1;194(7): 3400-3413 A, Owusu M, Nkrumah EE, Maganga confirms PNPLA3 and identifies Oldenburg J. Two enzymes catalyze GD, Oppong S, Adu-Sarkodie Y, Vallo TM6SF2 and MBOAT7 as risk loci for vitamin K 2,3-epoxide reductase Coenen M, Hinze AV, Mengel P, da Silva Filho LV, Leroy EM, Thiel V, alcohol-related cirrhosis. Nat. Genet. activity in mouse: VKORC1 is highly M, Fuhrmann C, Lüdenbach B, van der Hoek L, Poon LL, Tschapka 2015 Dec 1;47(12): 1443-1448 expressed in exocrine tissues while Zimmermann J, Dykstra V, Fimmers M, Drosten C, Drexler JF. Evidence VKORC1L1 is highly expressed in R, Viviani R, Stingl J, Holdenrieder for an ancestral association of human Buchholz BM, Rüland A, Kiefer N, brain. Thromb. Res. 2015 May S, Müller M, Hartmann G, Coch C. coronavirus 229E with bats. J. Virol. Poetzsch B, von Websky M, Kalff JC, 1;135(5): 977-983 Immune- and miRNA-response to 2015 Dec 1;89(23): 11858-11870 Merz WM. Conception, Pregnancy, recombinant interferon beta-1a: a

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Corman VM, Grundhoff A, Baechlein A, Baune BT, Heindel W, Domschke After Repeated Ivermectin Treatment: V, Matzner U, Brüstle O, Koch C, Fischer N, Gmyl A, Wollny R, K, Forstner A, Nöthen MM, Treutlein A Randomized, Placebo-Controlled, P. Arylsulfatase A Overexpressing Dei D, Ritz D, Binger T, Adankwah J, Arolt V, Hohoff C, Rietschel M, Double-Blind Trial. Clin. Infect. Dis. Human iPSC-derived Neural Cells E, Marfo KS, Annison L, Annan A, Witt SH. NCAN Cross-Disorder Risk 2015 Aug 15;61(4): 517-526 Reduce CNS Sulfatide Storage in Adu-Sarkodie Y, Oppong S, Becher Variant is Associated with Limbic a Mouse Model of Metachromatic P, Drosten C, Drexler JF. Highly Gray Matter Deficits in Healthy Di Marzo V, Stella N, Zimmer A. Leukodystrophy. Mol. Ther. 2015 divergent hepaciviruses from African Subjects and Major Depression. Endocannabinoid signalling and Sep 1;23(9): 1519-1531 cattle. J. Virol. 2015 Jun 1;89(11): Neuropsychopharmacology 2015 the deteriorating brain. Nat. Rev. 5876-5882 Oct 1;40(11): 2510-2516 Neurosci. 2015 Jan 1;16(1): 30-42 Dold L, Ahlenstiel G, Althausen E, Luda C, Schwarze-Zander C, Curcio M, Bradke F. Microtubule de Angelis MH, Nicholson G, Selloum Didovic S, Opitz FV, Holzmann B, Boesecke C, Wasmuth JC, Rockstroh Organization in the Axon: TRIM46 M, White JK, Morgan H, Ramirez- Förster I, Weighardt H. Requirement JK, Spengler U. Survival and Determines the Orientation. Neuron Solis R, [...] Zimmer A, [...] Steel of MyD88 signaling in keratinocytes HLA-B*57 in HIV/HCV Co-Infected 2015 Dec 16;88(6): 1072-1075 KP, Herault Y, Gailus-Durner V, for Langerhans cell migration and Patients on Highly Active Antiretroviral Mallon AM, Brown SD. Analysis of initiation of atopic dermatitis-like Therapy (HAART). PLoS ONE 2015 Czogalla KJ, Watzka M, Oldenburg mammalian gene function through symptoms in mice. Eur. J. Immunol. Jan 1;10(8): e0134158 J. Structural Modeling Insights broad-based phenotypic screens 2015 Dec 23 into Human VKORC1 Phenotypes. across a consortium of mouse clinics. Draaken M, Knapp M, Pennimpede Nutrients 2015 Aug 1;7(8): 6837- Nat. Genet. 2015 Sep 1;47(9): 969- Disteldorf EM, Krebs CF, Paust T, Schmidt JM, Ebert AK, Rösch W, 6851 978 HJ, Turner JE, Nouailles G, Tittel A, Stein R, Utsch B, Hirsch K, Boemers Meyer-Schwesinger C, Stege G, Brix TM, Mangold E, Heilmann S, Ludwig DaErme AM, Wilsmann-Theis D, Debette S, Ibrahim Verbaas CA, S, Velden J, Wiech T, Helmchen U, KU, Jenetzky E, Zwink N, Moebus S, Wagenpfeil J, Hölzel M, Ferring- Bressler J, Schuur M, Smith A, [...] Steinmetz OM, Peters A, Bennstein Herrmann BG, Mattheisen M, Nöthen Schmitt S, Sternberg S, Wittmann M, Nöthen MM,[...] van Duijn CM, Launer SB, Kaffke A, Llanto C, Lira SA, MM, Ludwig M, Reutter H. Genome- Peters B, Bosio A, Bieber T, Wenzel L, Fitzpatrick AL, Seshadri S, Mosley Mittrücker HW, Stahl RA, Kurts C, wide Association Study and Meta- J. IL-36 (IL-1F9) is a Biomarker for TH, . Genome-wide Studies of Verbal Kaufmann SH, Panzer U. CXCL5 Analysis Identify ISL1 as Genome- Psoriasis Skin Lesions. J. Invest. Declarative Memory in Nondemented Drives Neutrophil Recruitment in wide Significant Susceptibility Gene Dermatol.γ 2015 Apr 1;135(4): 1025- Older People: The Cohorts for Heart TH17-Mediated GN. J. Am. Soc. for Bladder Exstrophy. PLoS Genet. 1032 and Aging Research in Genomic Nephrol. 2015 Jan 1;26(1): 55-66 2015 Mar 1;11(3): e1005024 Epidemiology Consortium. Biol. Dankowski T, Buck D, Andlauer TF, Psychiatry 2015 Apr 15;77(8): 749- Djudjaj S, Lue H, Rong S, Dressen K, Hermann N, Manekeller Antony G, Bayas A, [...] Nöthen 763 Papasotiriou M, Klinkhammer S, Walgenbach-Bruenagel G, MM, [...] Zettl UK, Ziemann U, Zipp BM, Zok S, Klaener O, Braun GS, Schildberg FA, Hettwer K, Uhlig S, F, Hemmer B, Ziegler A. Successful Debrah AY, Specht S, Klarmann- Lindenmeyer MT, Cohen CD, Bucala Kalff JC, Holdenrieder S. Apoptosis- Replication of GWAS Hits for Multiple Schulz U, Batsa L, Mand S, Marfo- R, Tittel AP, Kurts C, Moeller MJ, related biomarkers in patients with Sclerosis in 10,000 Germans Using Debrekyei Y, Fimmers R, Dubben Floege J, Ostendorf T, Bernhagen gastrointestinal cancer. Int J Clin the Exome Array. Genet. Epidemiol. B, Kwarteng A, Osei-Atweneboana J, Boor P. Macrophage Migration Pharmacol Ther 2015 Dec 1;53(12): 2015 Dec 1;39(8): 601-608 M, Boakye D, Ricchiuto A, Büttner Inhibitory Factor Mediates Proliferative 1062-1064 M, Adjei O, Mackenzie CD, Hoerauf GN via CD74. J. Am. Soc. Nephrol. Dannlowski U, Kugel H, Grotegerd A. Doxycycline Leads to Sterility 2015 Oct 9 Drexler JF, Corman VM, Lukashev D, Redlich R, Suchy J, Opel N, and Enhanced Killing of Female AN, van den Brand JM, Gmyl AP, Suslow T, Konrad C, Ohrmann P, Onchocerca volvulus Worms in an Doerr J, Böckenhoff A, Ewald B, Brünink S, Rasche A, Seggewi N, Bauer J, Kircher T, Krug A, Jansen Area With Persistent Microfilaridermia Ladewig J, Eckhardt M, Gieselmann Feng H, Leijten LM, Vallo P, Kuiken β

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T, Dotzauer A, Ulrich RG, Lemon SM, Teratol. 2015 Apr 1;103(4): 235-242 Senses Bacterial RNA in Human S, Elger CE, Becker AJ, Niehusmann Drosten C. Evolutionary origins of Monocytes and Plays a Nonredundant P. Large-scale analysis of viral nucleic hepatitis A virus in small mammals. Eckerle I, Annan A, Drosten C. Role for Recognition of Streptococcus acid spectrum in temporal lobe Proc. Natl. Acad. Sci. U.S.A. 2015 Response to the letter to the editor: pyogenes. J. Immunol. 2015 Aug epilepsy biopsies. Epilepsia 2015 Feb Dec 8;112(49): 15190-15195 Barasheed et al., ‚No evidence of 1;195(3): 1092-1099 1;56(2): 234-243 MERS-CoV in Ghanaian Hajj pilgrims: Drosten C, Muth D, Corman VM, cautious interpretation is needed‘. Ekumi KM, Paculova H, Lenasi Exner D, Kalff JC, Engelhart S, Exner Hussain R, Al Masri M, HajOmar Trop. Med. Int. Health 2015 Aug T, Pospichalova V, Bösken CA, M. [In Process Citation]. Zentralbl W, Landt O, Assiri A, Eckerle I, Al 1;20(8): 1123-1124 Rybarikova J, Bryja V, Geyer M, Chir 2015 Oct 1;140 Suppl 1(): Shangiti A, Al-Tawfiq JA, Albarrak A, Blazek D, Barboric M. Ovarian S57-S72 Zumla A, Rambaut A, Memish ZA. Eckerle I, Kapaun A, Junghanss T, carcinoma CDK12 mutations An Observational, Laboratory-Based Schnitzler P, Drosten C, Jänisch T. misregulate expression of DNA repair Fassl SK, Austermann J, Study of Outbreaks of Middle East Dengue virus serotype 3 infection in genes via deficient formation and Papantonopoulou O, Riemenschneider Respiratory Syndrome Coronavirus traveler returning from west Africa function of the Cdk12/CycK complex. M, Xue J, Bertheloot D, Freise N, in Jeddah and Riyadh, Kingdom of to Germany. Emerging Infect. Dis. Nucleic Acids Res. 2015 Mar Spiekermann C, Witten A, Viemann Saudi Arabia, 2014. Clin. Infect. Dis. 2015 Jan 1;21(1): 175-177 11;43(5): 2575-2589 D, Kirschnek S, Stoll M, Latz 2015 Feb 1;60(3): 369-377 E, Schultze JL, Roth J, Vogl T. Ehret F, Vogler S, Pojar S, Elliott DA, Engel DR, Krause TA, Snelgrove Transcriptome Assessment Reveals Drosten C. What transmission trees Bradke F, Steiner B, Kempermann SL, Thiebes S, Hickey MJ, Boor a Dominant Role for TLR4 in the reveal about Ebola. Lancet Infect Dis G. Mouse model of CADASIL reveals P, Kitching AR, Kurts C. CX3CR1 Activation of Human Monocytes by 2015 Mar 1;15(3): 258-259 novel insights into Notch3 function Reduces Kidney Fibrosis by Inhibiting the Alarmin MRP8. J. Immunol. 2015 in adult hippocampal neurogenesis. Local Proliferation of Profibrotic Jan 15;194(2): 575-583 Duerr GD, Heinemann JC, Gestrich Neurobiol. Dis. 2015 Mar 1;75(): 131- Macrophages. J. Immunol. 2015 Feb C, Heuft T, Klaas T, Keppel K, Roell 141 15;194(4): 1628-1638 Fechner S, Alvarez L, Bönigk W, Klein A, Zimmer A, Velten M, W, Müller A, Berger T, Pascal R, Kilic A, Bindila L, Lutz B, Dewald O. Ehrhardt M, Craveiro RB, Holst MI, Eslam M, Hashem AM, Leung R, Trötschel C, Poetsch A, Stölting G, Impaired border zone formation and Pietsch T, Dilloo D. The PI3K inhibitor Romero-Gomez M, Berg T, Dore Siegfried KR, Kremmer E, Seifert R, adverse remodeling after reperfused GDC-0941 displays promising GJ, Chan HL, Irving WL, Sheridan Kaupp UB. A K(+)-selective CNG myocardial infarction in cannabinoid in vitro and in vivo efficacy for D, Abate ML, Adams LA, Mangia A, channel orchestrates Ca2(+) signalling CB2 receptor deficient mice. Life Sci. targeted medulloblastoma therapy. Weltman M, Bugianesi E, Spengler in zebrafish sperm. Elife 2015 Jan 1 2015 Oct 1;138(): 8-17 Oncotarget 2015 Jan 20;6(2): 802- U, Shaker O, Fischer J, Mollison L, 813 Cheng W, Powell E, Nattermann J, Fischer A, Ellinghaus D, Nutsua M, Dworschak GC, Draaken M, Riordan S, McLeod D, Armstrong NJ, Hofmann S, Montgomery CG, [...] Hilger AC, Schramm C, Bartels E, Eickhoff S, Brewitz A, Gerner MY, Douglas MW, Liddle C, Booth DR, Nöthen MM, [...] Lieb W, Nebel Schmiedeke E, Grasshoff-Derr S, Klauschen F, Komander K, Hemmi George J, Ahlenstiel G. Interferon-λ A, Müller-Quernheim J, Franke Märzheuser S, Holland-Cunz S, H, Garbi N, Kaisho T, Germain RN, rs12979860 genotype and liver A, Schreiber S. Identification of Lacher M, Jenetzky E, Zwink N, Kastenmüller W. Robust Anti-viral fibrosis in viral and non-viral chronic Immune-relevant Factors Conferring Schmidt D, Nöthen MM, Ludwig M, Immunity Requires Multiple Distinct T liver disease. Nat Commun 2015 Jan Sarcoidosis Genetic Risk. Am. J. Reutter H. Genome-wide mapping Cell-Dendritic Cell Interactions. Cell 1;6(): 6422 Respir. Crit. Care Med. 2015 Sep of copy number variations in patients 2015 Sep 10;162(6): 1322-1337 15;192(6): 727-736 with both anorectal malformations and Esposito L, Drexler JF, Braganza O, central nervous system abnormalities. Eigenbrod T, Pelka K, Latz E, Doberentz E, Grote A, Widman G, Forstner AJ, Hofmann A, Maaser Birth Defects Res. Part A Clin. Mol. Kreikemeyer B, Dalpke AH. TLR8 Drosten C, Eis-Hübinger AM, Schoch A, Sumer S, Khudayberdiev S, [...]

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Becker T, Rietschel M, Cichon S, Fröhlich H, Bahamondez G, Götschel Gestrich C, Duerr GD, Heinemann of the Middle Eastern Respiratory Schratt G, Nöthen MM. Genome- F, Korf U. Dynamic Bayesian Network JC, Meertz A, Probst C, Roell W, Syndrome Coronavirus Spike Protein wide analysis implicates microRNAs Modeling of the Interplay between Schiller W, Zimmer A, Bindila in Infected Cells but Does Not Reduce and their target genes in the EGFR and Hedgehog Signaling. PLoS L, Lutz B, Welz A, Dewald O. Viral Infectivity. J. Infect. Dis. 2015 development of bipolar disorder. ONE 2015 Jan 1;10(11): e0142646 Activation of Endocannabinoid Mar 15;211(6): 889-897 Transl Psychiatry 2015 Jan 1;5(): System Is Associated with Persistent e678 Fröhlich H. biRte: Bayesian inference Inflammation in Human Aortic Ginhoux F, Schultze JL, Murray PJ, of context-specific regulator activities Aneurysm. Biomed Res Int 2015 Jan Ochando J, Biswas SK. 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The Immune Eubanks LM, Hoerauf A, Janda KD. 1;20(7): 913 transcatheter aortic valve in a case Checkpoint Regulator PD-L1 Is Highly Litomosoides sigmodontis: A jird urine of prosthesis frame underexpansion Expressed in Aggressive Primary metabolome study. Bioorg. Med. Franken L, Klein M, Spasova M, due to leaflet calcification. JACC Prostate Cancer. Clin. Cancer Res. Chem. Lett. 2015 Dec 15;25(24): Elsukova A, Wiedwald U, Welz M, Cardiovasc Interv 2015 May 1;8(6): 2015 Nov 16 5804-5807 Knolle P, Farle M, Limmer A, Kurts 866-868 C. Splenic red pulp macrophages are Geyer M, Pelka K, Latz E. Synergistic Glodde N, Jakobs M, Bald T, intrinsically superparamagnetic and Fuchs FC, Hammerstingl C, Sinning activation of Toll-like receptor 8 by Tüting T, Gaffal E. Differential role contaminate magnetic cell isolates. JM, Mellert F, Werner N, Grube E, two RNA degradation products. Nat. of cannabinoids in the pathogenesis Sci Rep 2015 Jan 1;5(): 12940 Nickenig G. Antegrade transcatheter Struct. 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Eight Novel Mutations postoperative intestinal inflammation bats from Africa. PLoS ONE 2015 Annuloplasty Ring. JACC Cardiovasc Confirm the Role of AAGAB in and prevents postoperative ileus. Jan 1;10(5): e0127035 Interv 2015 Dec 28;8(15): e263-e264 Punctate Palmoplantar Keratoderma Neurogastroenterol. Motil. 2015 Jul Type 1 (Buschke-Fischer-Brauer) and 1;27(7): 1038-1049 Freuling CM, Binger T, Beer M, Gaulton KJ, Ferreira T, Lee Y, Show Broad Phenotypic Variability. Adu-Sarkodie Y, Schatz J, Fischer Raimondo A, Mägi R, [...] Nöthen MM Acta Derm. Venereol. 2015 Nov 26 Glowka TR, Wei L, Hata K, Afify M, M, Hanke D, Hoffmann B, Höper [...] Altshuler D, Boehnke M, Teslovich Kalff JC, Minor T, Tolba RH. Oxygen D, Mettenleiter TC, Oppong SK, TM, McCarthy MI, Morris AP,. Genetic Gierer S, Müller MA, Heurich A, Insufflation in University of Wisconsin Drosten C, Müller T. Lagos bat virus fine mapping and genomic annotation Ritz D, Springstein BL, Karsten CB, Solution Ameliorates Reperfusion transmission in an Eidolon helvum bat defines causal mechanisms at type 2 Schendzielorz A, Gnirß K, Drosten C, Injury in Small Bowel after Cold colony, Ghana. Virus Res. 2015 Dec diabetes susceptibility loci. Nat. Genet. Pöhlmann S. Inhibition of Proprotein Storage and Reperfusion. Ann. 2;210(): 42-45 2015 Dec 1;47(12): 1415-1425 Convertases Abrogates Processing Transplant. 2015 Jan 1;20(): 469-477

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Goldmann G, Berens C, Marquardt N, Macrophages. PLoS Pathog. 2015 W, Irsen S, Noé F, Kaupp UB, 21;51(6): 1135-1138 Reich R, Oldenburg J, Wenghoefer Jan 1;11(1): e1004616 Al-Amoudi A. Higher-Order M. No increased bleeding risk for Architecture of Rhodopsin in Intact Hasenberg A, Hasenberg M, Männ L, oral surgery in patients with severe Gorris R, Fischer J, Erwes KL, Photoreceptors and Its Implication for Neumann F, Borkenstein L, Stecher congenital bleeding disorders due to Kesavan J, Peterson DA, Alexander Phototransduction Kinetics. Structure M, Kraus A, Engel DR, Klingberg A, intense perioperative management. M, Nöthen MM, Peitz M, Quandel 2015 Apr 7;23(4): 628-638 Seddigh P, Abdullah Z, Klebow S, Oral Maxillofac Surg 2015 Jun T, Karus M, Brüstle O. Pluripotent Engelmann S, Reinhold A, Brandau S, 1;19(2): 195-200 stem cell-derived radial glia-like Günther C, Kind B, Reijns MA, Seeling M, Waisman A, Schraven B, cells as stable intermediate for Berndt N, Martinez-Bueno M, [...] Göthert JR, Nimmerjahn F, Gunzer M. Goldmann G, Marquardt N, efficient generation of human Nöthen MM, [...] Dahl A, Roers A, Catchup: a mouse model for imaging- Horneff S, Oldenburg J, Zeitler H. oligodendrocytes. Glia 2015 Dec Alarcon-Riquelme ME, Jackson AP, based tracking and modulation Treatment of minor severe acquired 1;63(12): 2152-2167 Lee-Kirsch MA. Defective removal of of neutrophil granulocytes. Nat. haemophilia. Is there a rationale for ribonucleotides from DNA promotes Methods 2015 May 1;12(5): 445-452 immunoadsorption? Atheroscler Görtzen J, Schierwagen R, Bierwolf J, systemic autoimmunity. J. Clin. Suppl 2015 May 1;18(): 74-79 Klein S, Uschner FE, van der Ven PF, Invest. 2015 Jan 1;125(1): 413-424 Hecker J, Prokopenko D, Lange Fürst DO, Strassburg CP, Laleman C, Fier HL. On the Recombination Goldmann G, Zeitler H, Marquardt N, W, Pollok JM, Trebicka J. Interplay of Haas N, Riedt T, Labbaf Z, Baßler K, Rate Estimation in the Presence of Horneff S, Balta Z, Strassburg CP, Matrix Stiffness and c-SRC in Hepatic Gergis D, Fröhlich H, Gütgemann I, Population Substructure. PLoS ONE Oldenburg J. Long-term outcome Fibrosis. Front Physiol 2015 Jan Janzen V, Schorle H. Kit transduced 2015 Jan 1;10(12): e0145152 of liver transplantation in HCV/HIV 1;6(): 359 signals counteract erythroid coinfected haemophilia patients. A maturation by MAPK-dependent Heilbronner U, Malzahn D, Strohmaier single centre study of 10 patients. Gotot J, Piotrowski E, Otte MS, Tittel modulation of erythropoietin signaling J, Maier S, Frank J, Treutlein J, Hamostaseologie 2015 Jan 1;35(2): AP, Linlin G, Yao C, Ziegelbauer K, and apoptosis induction in mouse Mühleisen TW, Forstner AJ, Witt SH, 175-180 Panzer U, Garbi N, Kurts C, Thaiss fetal liver. Cell Death Differ. 2015 Cichon S, Falkai P, Nöthen MM, F. Inhibitor of NF B Kinase Subunit May 1;22(5): 790-800 Rietschel M, Schulze TG. A common Gollasch B, Basmanav FB, Nanda 2 Blockade Hinders the Initiation risk variant in CACNA1C supports a A, Fritz G, Mahmoudi H, Thiele but Aggravates theκ Progression of Habib R, Ansar M, Mattheisen M, sex-dependent effect on longitudinal H, Wehner M, Wolf S, Altmüller J, Crescentic GN. J. Am. Soc. Nephrol. Shahid M, Ali G, Ahmad W, Betz functioning and functional recovery Nürnberg P, Frank J, Betz RC. 2015 Nov 16 RC. A Novel Locus for Ectodermal from episodes of schizophrenia- Identification of a novel mutation in Dysplasia of Hair, Nail and Skin spectrum but not bipolar disorder. Eur RIPK4 in a kindred with phenotypic Gottschalk C, Kurts C. The Pigmentation Anomalies Maps to Neuropsychopharmacol 2015 Dec features of Bartsocas-Papas and Debate about Dendritic Cells and Chromosome 18p11.32-p11.31. 1;25(12): 2262-2270 CHAND syndromes. Am. J. Med. Macrophages in the Kidney. Front PLoS ONE 2015 Jan 1;10(6): Genet. A 2015 Nov 1;167A(11): Immunol 2015 Jan 1;6(): 435 e0129811 Heilmann S, Drichel D, Clarimon J, 2555-2562 Fernández V, Lacour A, Wagner H, Gottschalk C, Mettke E, Kurts C. The Hamedani NS, Blümke F, Tolle F, Thelen M, Hernández I, Fortea J, Gondorf F, Berbudi A, Buerfent BC, Role of Invariant Natural Killer T Cells Rohrbach F, Rühl H, Oldenburg Alegret M, Blesa R, Mauleón A, Roca Ajendra J, Bloemker D, Specht S, in Dendritic Cell Licensing, Cross- J, Mayer G, Pötzsch B, Müller MR, Kornhuber J, Peters O, Heun R, Schmidt D, Neumann AL, Layland Priming, and Memory CD8(+) T Cell J. Capture and Release (CaR): a Frölich L, Hüll M, Heneka MT, Rüther LE, Hoerauf A, Hübner MP. Generation. Front Immunol 2015 Jan simplified procedure for one-tube E, Riedel-Heller S, Scherer M, Wiltfang Chronic Filarial Infection Provides 1;6(): 379 isolation and concentration of J, Jessen F, Becker T, Tárraga L, Protection against Bacterial Sepsis single-stranded DNA during SELEX. Boada M, Maier W, Lleó A, Ruiz A, by Functionally Reprogramming Gunkel M, Schöneberg J, Alkhaldi Chem. Commun. (Camb.) 2015 Jan Nöthen MM, Ramirez A. PLD3 in

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non-familial Alzheimer‘s disease. G. Effect of pioglitazone medication Arias-Vasquez A, Desrivières S, JP, Oldenburg J, Tiede A, Male C, Nature 2015 Apr 2;520(7545): E3-E5 on the incidence of dementia. Ann. J [...] Nöthen MM [...]Wright MJ, Windyga J, Greinacher A, Knöbl PN, Neurol. 2015 Aug 1;78(2): 284-294 Schumann G, Franke B, Thompson Schrenk G, Koehn J, Scheiflinger F, Heine A, Brossart P. A party of PM, Medland SE. Common genetic Reipert BM. Affinity of FVIII-specific three: iNKT cells in GVHD prevention. Heneka MT, Golenbock DT, Latz variants influence human subcortical antibodies reveals major differences BLOOD. 2015 May 28;125(22): 3374- E. Innate immunity in Alzheimer‘s brain structures. Nature 2015 Apr between neutralizing and non- 3375 disease. Nat. Immunol. 2015 Mar 9;520(7546): 224-229 neutralizing antibodies. BLOOD 2015 1;16(3): 229-236 Feb 12;125(7): 1180-1188 Heine A, Held SA, Daecke SN, Hilger AC, Halbritter J, Pennimpede Riethausen K, Kotthoff P, Flores C, Herold M, Posevitz V, Chudyka D, T, van der Ven A, Sarma G, Braun Hoffmann F, Schmidt A, Dittmann Kurts C, Brossart P. The VEGF- Hucke S, Groß C, Kurth F, Leder C, DA, Porath JD, Kohl S, Hwang Chevillotte M, Wisskirchen C, Receptor Inhibitor Axitinib Impairs Loser K, Kurts C, Knolle P, Klotz L, DY, Dworschak GC, Hermann BG, Hellmuth JC, Willms S, Gilmore Dendritic Cell Phenotype and Wiendl H. B7-H1 Selectively Controls Pavlova A, El-Maarri O, Nöthen MM, RH, Glas J, Folwaczny M, Müller T, Function. PLoS ONE 2015 Jan TH17 Differentiation and Central Ludwig M, Reutter H, Hildebrandt Berg T, Spengler U, Fitzmaurice 1;10(6): e0128897 Nervous System Autoimmunity via a F. Targeted Resequencing of 29 K, Kelleher D, Reisch N, Rice Novel Non-PD-1-Mediated Pathway. Candidate Genes and Mouse CM, Endres S, Rothenfusser S. Heinemann JC, Duerr GD, Keppel J. Immunol. 2015 Oct 15;195(8): Expression Studies Implicate ZIC3 Polymorphisms in MDA-5 link protein K, Breitbach M, Fleischmann 3584-3595 and FOXF1 in Human VATER/ function to clearance of hepatitis C BK, Zimmer A, Wehner S, Welz VACTERL Association. Hum. Mutat. virus. Hepatology 2015 Feb 1;61(2): A, Dewald O. CB2 receptor- Herzner AM, Hagmann CA, Goldeck 2015 Dec 1;36(12): 1150-1154 460-470 mediated effects of pro-inflammatory M, Wolter S, Kübler K, Wittmann S, macrophages influence survival of Gramberg T, Andreeva L, Hopfner Hiller B, Hornung V. STING Signaling Holtick U, Frenzel LP, Shimabukuro- cardiomyocytes. Life Sci. 2015 Oct KP, Mertens C, Zillinger T, Jin T, Xiao the enERGIC Way. Cell Host Vornhagen A, Theurich S, Claasen J, 1;138(): 18-28 TS, Bartok E, Coch C, Ackermann D, Microbe 2015 Aug 12;18(2): 137-139 Scheid C, von Bergwelt-Baildon M, Hornung V, Ludwig J, Barchet W, Fröhlich H, Wendtner CM, Chemnitz Heneka MT, Carson MJ, Khoury JE, Hartmann G, Schlee M. Sequence- Hochheiser K, Kurts C. Selective JM. CD4+ T cell counts reflect the Landreth GE, Brosseron F, Feinstein specific activation of the DNA sensor Dependence of Kidney Dendritic immunosuppressive state of CD4 DL, Jacobs AH, Wyss-Coray T, cGAS by Y-form DNA structures as Cells on CX3CR1-Implications for helper cells in patients after allogeneic Vitorica J, Ransohoff RM, Herrup found in primary HIV-1 cDNA. Nat. Glomerulonephritis Therapy. Adv. Exp. stem cell transplantation. Ann. K, Frautschy SA, Finsen B, Brown Immunol. 2015 Oct 1;16(10): 1025- Med. Biol. 2015 Jan 1;850(): 55-71 Hematol. 2015 Jan 1;94(1): 129-137 GC, Verkhratsky A, Yamanaka K, 1033 Koistinaho J, Latz E, Halle A, Petzold Höchst B, Mikulec J, Baccega T, Hong G, Vilz TO, Kalff JC, Wehner GC, Town T, Morgan D, Shinohara Heymann F, Peusquens J, Ludwig- Metzger C, Welz M, Peusquens J, S. [Peritoneal adhesion formation]. ML, Perry VH, Holmes C, Bazan Portugall I, Kohlhepp M, Ergen C, Tacke F, Knolle P, Kurts C, Diehl Chirurg 2015 Feb 1;86(2): 175-180 NG, Brooks DJ, Hunot S, Joseph Niemietz P, Martin C, van Rooijen N, L, Ludwig-Portugall I. Differential B, Deigendesch N, Garaschuk O, Ochando JC, Randolph GJ, Luedde Induction of Ly6G and Ly6C Positive Hong GS, Schwandt T, Stein K, Boddeke E, Dinarello CA, Breitner JC, T, Ginhoux F, Kurts C, Trautwein C, Myeloid Derived Suppressor Cells in Schneiker B, Kummer MP, Heneka Cole GM, Golenbock DT, Kummer Tacke F. Liver inflammation abrogates Chronic Kidney and Liver Inflammation MT, Kitamura K, Kalff JC, Wehner MP. Neuroinflammation in Alzheimer‘s immunological tolerance induced by and Fibrosis. PLoS ONE 2015 Jan S. Effects of macrophage-dependent disease. Lancet Neurol 2015 Apr Kupffer cells. Hepatology 2015 Jul 1;10(3): e0119662 peroxisome proliferator-activated 1;14(4): 388-405 1;62(1): 279-291 receptor γ signalling on adhesion Hofbauer CJ, Whelan SF, Hirschler formation after abdominal surgery in Heneka MT, Fink A, Doblhammer Hibar DP, Stein JL, Renteria ME, M, Allacher P, Horling FM, Lawo an experimental model. Br J Surg

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2015 Nov 1;102(12): 1506-1516 Hückesfeld S, Schoofs A, Schlegel 2015 Jan 1;35 Suppl 1(): S27-S31 Jansen F, Yang X, Nickenig G, P, Miroschnikow A, Pankratz MJ. Werner N, Vasa-Nicotera M. Role, Hopt U, Ghadimi M, Kalff J. [In Localization of Motor Neurons and Jaeger M, van der Lee R, Cheng Function and Therapeutic Potential of Process Citation]. Zentralbl Chir Central Pattern Generators for Motor SC, Johnson MD, Kumar V, Ng A, microRNAs in Vascular Aging. Curr 2015 Dec 1;140(6): 583-584 Patterns Underlying Feeding Behavior Plantinga TS, Smeekens SP, Oosting Vasc Pharmacol 2015 Jan 1;13(3): in Drosophila Larvae. PLoS ONE M, Wang X, Barchet W, Fitzgerald 324-330 Horpaopan S, Spier I, Zink AM, 2015 Jan 1;10(8): e0135011 K, Joosten LA, Perfect JR, Wijmenga Altmüller J, Holzapfel S, Laner A, Vogt C, van de Veerdonk FL, Huynen MA, Jansen V, Alvarez L, Balbach M, S, Uhlhaas S, Heilmann S, Stienen Humme D, Haider A, Möbs M, Mitsui Xavier RJ, Kullberg BJ, Netea MG. Strünker T, Hegemann P, Kaupp UB, D, Pasternack SM, Keppler K, Adam H, Suárez-Fariñas M, Ohmatsu The RIG-I-like helicase receptor MDA5 Wachten D. Controlling fertilization R, Kayser K, Moebus S, Draaken M, H, Isabell Geilen C, Eberle J, (IFIH1) is involved in the host defense and cAMP signaling in sperm by Degenhardt F, Engels H, Hofmann Krueger JG, Beyer M, Hummel M, against Candida infections. Eur. J. optogenetics. Elife 2015 Jan 1 A, Nöthen MM, Steinke V, Perez- Anagnostopoulos I, Sterry W, Assaf Clin. Microbiol. Infect. Dis. 2015 Bouza A, Herms S, Holinski-Feder E, C. Aurora Kinase A Is Upregulated May 1;34(5): 963-974 Jenniches I, Ternes S, Albayram O, Fröhlich H, Thiele H, Hoffmann P, in Cutaneous T-Cell Lymphoma and Otte DM, Bach K, Bindila L, Michel Aretz S. Genome-wide CNV analysis Represents a Potential Therapeutic Jakobs C, Perner S, Hornung V. K, Lutz B, Bilkei-Gorzo A, Zimmer A. in 221 unrelated patients and targeted Target. J. Invest. Dermatol. 2015 AIM2 Drives Joint Inflammation in a Anxiety, Stress, and Fear Response in high-throughput sequencing reveal Sep 1;135(9): 2292-2300 Self-DNA Triggered Model of Chronic Mice with Reduced Endocannabinoid novel causative candidate genes for Polyarthritis. PLoS ONE 2015 Jan Levels. Biol. Psychiatry 2015 Apr 14 colorectal adenomatous polyposis. Ibsen MS, Gad HH, Andersen LL, 1;10(6): e0131702 Int. J. Cancer 2015 Mar 15;136(6): Hornung V, Julkunen I, Sarkar SN, Jenniches I, Zimmer A. Reply E578-E589 Hartmann R. Structural and functional Jansen C, Reiberger T, Huang To: The Anxiolytic Actions of analysis reveals that human OASL J, Eischeid H, Schierwagen R, 2-Arachidonoylglycerol: Converging Hosp F, Vossfeldt H, Heinig M, binds dsRNA to enhance RIG-I Mandorfer M, Anadol E, Schwabl P, Evidence from Two Recent Genetic Vasiljevic D, Arumughan A, Wyler E,, signaling. Nucleic Acids Res. 2015 Schwarze-Zander C, Warnecke-Eberz Endocannabinoid Deficiency Models. Nöthen MM, Landthaler M, Hubner May 26;43(10): 5236-5248 U, Strassburg CP, Rockstroh JK, Biol. Psychiatry 2015 Jul 2 N, Wanker EE, Lannfelt L, Ingelsson Peck-Radosavljevic M, Odenthal M, M, Lalowski M, Voigt A, Selbach M. Ivaškevičius V, Goldmann G, Trebicka J. Circulating MiRNA-122 Jikeli JF, Alvarez L, Friedrich BM, Quantitative interaction proteomics of Biswas A, Westhofen P, Thomas Levels Are Associated with Hepatic Wilson LG, Pascal R, Colin R, neurodegenerative disease proteins. A, Marquardt N, Horneff S, Klein Necroinflammation and Portal Pichlo M, Rennhack A, Brenker C, Cell Rep 2015 May 19;11(7): 1134- C, Rühl H, Pötzsch B, Oldenburg Hypertension in HIV/HCV Coinfection. Kaupp UB. Sperm navigation along 1146 J. Neoplasm-induced bleeding PLoS ONE 2015 Jan 1;10(2): helical paths in 3D chemoattractant in inherited, heterozygous FXIII-A e0116768 landscapes. Nat Commun 2015 Jan Hotz A, Oji V, Bourrat E, Jonca N, deficiency. Hamostaseologie 2015 1;6(): 7985 Mazereeuw-Hautier J, Betz RC, Jan 1;35 Suppl 1(): S32-S35 Jansen F, Yang X, Baumann K, Blume-Peytavi U, Stieler K, Morice- Przybilla D, Schmitz T, Flender A, Paul Junglen S, Marklewitz M, Zirkel F, Picard F, Schönbuchner I, Markus Ivaškevičius V, Thomas A, Biswas K, Alhusseiny A, Nickenig G, Werner Wollny R, Meyer B, Heidemann H, S, Schlipf N, Fischer J. Expanding A, Ensikat H, Schmitt U, Horneff S, N. Endothelial microparticles reduce Metzger S, Annan A, Dei D, Leendertz the Clinical and Genetic Spectrum of Pavlova A, Poetzsch B, Oldenburg J. ICAM-1 expression in a microRNA- FH, Oppong S, Drosten C. No KRT1, KRT2 and KRT10 Mutations in A novel fibrinogen chain frameshift 222-dependent mechanism. J. Cell. Evidence of Gouléako and Herbert Keratinopathic Ichthyosis. Acta Derm. deletion (c.637delT) in a patient with Mol. Med. 2015 Sep 1;19(9): 2202- Virus Infections in Pigs, Côte d‘Ivoire Venereol. 2015 Nov 19 hypodysfibrinogenemiaγ associated 2214 and Ghana. Emerging Infect. Dis. with thrombosis. Hamostaseologie 2015 Dec 1;21(12): 2190-2193

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Krüger N, Hoffmann M, Drexler JF, Kummer MP, Schwarzenberger De Nardo D. ATF3 Is a Key Regulator NK Cells and Hepatic Stellate Cells Müller MA, Corman VM, Sauder C, R, Sayah-Jeanne S, Dubernet M, of Macrophage IFN Responses. J. (HSC) by Acting on either Cell Type. J. Rubin S, He B, Örvell C, Drosten C, Walczak R, Hum DW, Schwartz Immunol. 2015 Nov 1;195(9): 4446- Hepatol. 2015 Feb 1;62(2): 398-404 Herrler G. Functional properties and S, Axt D, Heneka MT. Pan-PPAR 4455 genetic relatedness of the fusion and Modulation Effectively Protects APP/ Lässig C, Matheisl S, Sparrer KM, de hemagglutinin-neuraminidase proteins PS1 Mice from Amyloid Deposition Lachmann N, Czarnecki K, Brennig Oliveira Mann CC, Moldt M, Patel JR, of a mumps virus-like bat virus. J. and Cognitive Deficits. Mol. S, Phaltane R, Heise M, Heinz Goldeck M, Hartmann G, García- Virol. 2015 Apr 1;89(8): 4539-4548 Neurobiol. 2015 Apr 1;51(2): 661- N, Kempf H, Dilloo D, Kaever V, Sastre A, Hornung V, Conzelmann 671 Schambach A, Heuser M, Moritz T. KK, Beckmann R, Hopfner KP. Kruschwitz JD, Walter M, Varikuti Deoxycytidine-kinase knockdown as a ATP hydrolysis by the viral RNA D, Jensen J, Plichta MM, Haddad Kunsleben N, Rüdrich U, Gehring novel myeloprotective strategy in the sensor RIG-I prevents unintentional L, Grimm O, Mohnke S, Pöhland L, M, Novak N, Kapp A, Raap U. IL- context of fludarabine, cytarabine or recognition of self-RNA. Elife 2015 Schott B, Wold A, Mühleisen TW, 31 induces Chemotaxis, Calcium cladribine therapy. Leukemia 2015 Jan 1;4 Heinz A, Erk S, Romanczuk-Seiferth Mobilization, Release of Reactive Nov 1;29(11): 2266-2269 N, Witt SH, Nöthen MM, Rietschel Oxygen Species and CCL26 in Layland LE, Ajendra J, Ritter M, Meyer-Lindenberg A, Walter H. Eosinophils which are Capable to Lacour A, Schüller V, Drichel D, M, Wiszniewsky A, Hoerauf A, 5-HTTLPR/rs25531 polymorphism Release IL-31. J. Invest. Dermatol. Herold C, Jessen F, Leber M, Maier Hübner MP. Development of patent and neuroticism are linked by resting 2015 Jul 1;135(7): 1908-1911 W, Noethen MM, Ramirez A, Litomosoides sigmodontis infections state functional connectivity of Vaitsiakhovich T, Becker T. Novel in semi-susceptible C57BL/6 mice amygdala and fusiform gyrus. Brain Kunz M, König IR, Schillert A, Kruppa genetic matching methods for in the absence of adaptive immune Struct Funct 2015 Jul 1;220(4): J, Ziegler A, Grallert H, Müller- handling population stratification in responses. Parasit Vectors 2015 Jan 2373-2385 Nurasyid M, Lieb W, Franke A, genome-wide association studies. 1;8(): 396 Ranki A, Panelius J, Koskenmies S, BMC Bioinformatics 2015 Jan Kühn S, Erdmann C, Kage F, Block Hasan T, Kere J, Rönn AC, Simon 1;16(): 84 Lee SH, Byrne EM, Hultman CM, J, Schwenkmezger L, Steffen A, JC, Schmidt E, Wenzel J, Tüting T, Kähler A, Vinkhuyzen AA, [...] Nöthen Rottner K, Geyer M. The structure Landsberg J, Zeller T, Blankenberg Lang PA, Meryk A, Pandyra AA, MM [...] Klareskog L, Mariette X, of FMNL2-Cdc42 yields insights into S, Gläser R, Patsinakidis N, Kuhn Brenner D, Brüstle A, Xu HC, Merches Plenge RM, van Laar M, van Riel the mechanism of lamellipodia and A, Ibrahim SM. Genome-wide K, Lang F, Khairnar V, Sharma P, P. New data and an old puzzle: filopodia formation. Nat Commun association study identifies new Funkner P, Recher M, Shaabani N, the negative association between 2015 Jan 1;6(): 7088 susceptibility loci for cutaneous lupus Duncan GS, Duhan V, Homey B, schizophrenia and rheumatoid erythematosus. Exp. Dermatol. 2015 Ohashi PS, Häussinger D, Knolle PA, arthritis. Int J Epidemiol 2015 Aug 18 Kukuk GM, Hittatiya K, Sprinkart Jul 1;24(7): 510-515 Honke N, Mak TW, Lang KS. Toso AM, Eggers H, Gieseke J, Block W, regulates differentiation and activation Lekana-Douki SE, Kombila-Koumavor Moeller P, Willinek WA, Spengler Kurzwelly D, Krüger S, Biskup S, of inflammatory dendritic cells during C, Nkoghe D, Drosten C, Drexler JF, U, Trebicka J, Fischer HP, Schild Heneka MT. A distinct clinical persistence-prone virus infection. Cell Leroy EM. Molecular epidemiology HH, Träber F. Comparison between phenotype in a German kindred with Death Differ. 2015 Jan 1;22(1): 164- of enteric viruses and genotyping of modified Dixon MRI techniques, motor neuron disease carrying a 173 rotavirus A, adenovirus and astrovirus MR spectroscopic relaxometry, and CHCHD10 mutation. Brain 2015 Sep among children under 5 years old in different histologic quantification 1;138(Pt 9): e376 Langhans B, Alwan AW, Krämer Gabon. Int. J. Infect. Dis. 2015 May methods in the assessment of hepatic B, Glässner A, Lutz P, Strassburg 1;34(): 90-95 steatosis. Eur Radiol 2015 Oct Labzin LI, Schmidt SV, Masters SL, CP, Nattermann J, Spengler U. 1;25(10): 2869-2879 Beyer M, Krebs W, Klee K, Stahl R, Regulatory CD4(+) T cells (Tregs) Lentz CS, Sattler JM, Fendler M, Lütjohann D, Schultze JL, Latz E, Modulate the Interaction between Gottwalt S, Halls VS, Strassel S,

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Arriens S, Hannam JS, Specht S, M, Bergen SE, Landén M, Hultman Lissitchkov T, Hampton K, von Regulation of Anti-Tumor Immune Famulok M, Mueller AK, Hoerauf A, CM, Forstner AJ, Strohmaier J, Depka M, Hay C, Rangarajan S, Responses by Mesenchymal Stem Pfarr KM. In Vitro Activity of wALADin Hecker J, Schulze TG, Müller-Myhsok Tuddenham E, Holstein K, Huth- Cells. Front Immunol 2015 Jan 1;6(): Benzimidazoles against Different B, Reif A, Mitchell PB, Martin NG, Kühne A, Pabinger I, Knaub S, Bichler 645 Life Cycle Stages of Plasmodium Cichon S, Nöthen MM, Alkelai J, Oldenburg J. Novel, human cell Parasites. Antimicrob. Agents A, Lerer B, Jamain S, Leboyer M, line-derived recombinant factor VIII Lübkemeier I, Bosen F, Kim JS, Chemother. 2015 Jan 1;59(1): 654- Bellivier F, Etain B, Kahn JP, Henry (human-cl rhFVIII; Nuwiq(®) ) in adults Sasse P, Malan D, Fleischmann 658 C, Rietschel M. Convergent Lines with severe haemophilia A: efficacy BK, Willecke K. The Human of Evidence Support LRP8 as a and safety. Haemophilia 2015 Aug Connexin43E42K Mutation from a Lenz TL, Deutsch AJ, Han B, Hu Susceptibility Gene for Psychosis. 28 Sudden Infant Death Victim Leads X, Okada Y, [...] Nöthen MM, [...] Mol. Neurobiol. 2015 Dec 4 to Impaired Ventricular Activation Rich SS, Wijmenga C, Sunyaev Liu F, Hamer MA, Heilmann S, Herold and Neonatal Death in Mice. Circ SR, de Bakker PI, Raychaudhuri Li W, Zech I, Gieselmann V, Müller C, Moebus S, Hofman A, Uitterlinden Cardiovasc Genet 2015 Feb 1;8(1): S. Widespread non-additive and CE. A capillary electrophoresis AG, Nöthen MM, van Duijn CM, 21-29 interaction effects within HLA loci method with dynamic pH junction Nijsten TE, Kayser M. Prediction modulate the risk of autoimmune stacking for the monitoring of of male-pattern baldness from Luo XJ, Mattheisen M, Li M, Huang diseases. Nat. Genet. 2015 Sep cerebroside sulfotransferase. J genotypes. Eur. J. Hum. Genet. 2015 L, Rietschel M, Børglum AD, Als TD, 1;47(9): 1085-1090 Chromatogr A 2015 Aug 14;1407(): Oct 28 van den Oord EJ, Aberg KA, Mors O, 222-227 Mortensen PB, Luo Z, Degenhardt Levy M, Thaiss CA, Zeevi D, Locke AE, Kahali B, Berndt SI, Justice F, Cichon S, Schulze TG, Nöthen Dohnalová L, Zilberman-Schapira Lindlau A, Widmann CN, Putensen C, AE, Pers TH, [...] Nöthen MM [...], MM, Su B, Zhao Z, Gan L, Yao YG. G, Mahdi JA, David E, Savidor A, Jessen F, Semmler A, Heneka MT. North KE, Ingelsson E, Hirschhorn Systematic Integration of Brain eQTL Korem T, Herzig Y, Pevsner-Fischer Predictors of hippocampal atrophy in JN, Loos RJ, Speliotes EK. Genetic and GWAS Identifies ZNF323 as a M, Shapiro H, Christ A, Harmelin A, critically ill patients. Eur. J. Neurol. studies of body mass index yield new Novel Schizophrenia Risk Gene and Halpern Z, Latz E, Flavell RA, Amit 2015 Feb 1;22(2): 410-415 insights for obesity biology. Nature Suggests Recent Positive Selection I, Segal E, Elinav E. Microbiota- 2015 Feb 12;518(7538): 197-206 Based on Compensatory Advantage Modulated Metabolites Shape the Linhart M, Sinning JM, Ghanem on Pulmonary Function. Schizophr Intestinal Microenvironment by A, Kozhuppakalam FJ, Fistéra R, Louwersheimer E, Ramirez A, Bull 2015 Nov 1;41(6): 1294-1308 Regulating NLRP6 Inflammasome Hammerstingl C, Pizarro C, Grube E, Cruchaga C, Becker T, Kornhuber Signaling. Cell 2015 Dec 3;163(6): Werner N, Nickenig G, Skowasch J, Peters O, Heilmann S, Wiltfang Lutz P, Nischalke HD, Strassburg 1428-1443 D. Prevalence and Impact of Sleep J, Jessen F, Visser PJ, Scheltens CP, Spengler U. Spontaneous Disordered Breathing in Patients with P, Pijnenburg YA, Teunissen CE, bacterial peritonitis: The clinical Li J, Jørgensen SF, Maggadottir SM, Severe Aortic Stenosis. PLoS ONE Barkhof F, van Swieten JC, Holstege challenge of a leaky gut and a cirrhotic Bakay M, Warnatz K, [...] Nöthen 2015 Jan 1;10(7): e0133176 H, Van der Flier WM, . The influence of liver. World J Hepatol 2015 Mar MM,[...] Karlsen TH, Grimbacher B, genetic variants in SORL1 gene on the 27;7(3): 304-314 Hakonarson H, Hammarström L, Linz A, Knieper Y, Gronau T, Hansen manifestation of Alzheimer‘s disease. Ellinghaus E. Association of CLEC16A U, Aszodi A, Garbi N, Hämmerling Neurobiol. Aging 2015 Mar 1;36(3): Lutz P, Pfarr K, Nischalke HD, with human common variable GJ, Pap T, Bruckner P, Dreier R. ER 1605.e13-1605.e20 Krämer B, Goeser F, Glässner A, immunodeficiency disorder and role stress during the pubertal growth Wolter F, Kokordelis P, Nattermann in murine B cells. Nat Commun 2015 spurt results in impaired long bone Lu KH, Tounsi A, Shridhar N, J, Sauerbruch T, Hoerauf A, Jan 1;6(): 6804 growth in chondrocyte-specific ERp57 Küblbeck G, Klevenz A, Prokosch Strassburg CP, Spengler U. The knockout mice. J. Bone Miner. Res. S, Bald T, Tüting T, Arnold B. ratio of calprotectin to total protein as Li M, Huang L, Grigoroiu-Serbanescu 2015 Aug 1;30(8): 1481-1493 Dickkopf-3 Contributes to the a diagnostic and prognostic marker

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Pougialis G, Bestvater F, Klotz Virus-Infected Mice. Eur J Microbiol E, Alhakeem RF, Assiri AM, Albarrak 1;29(1): 8-14 L, Moldenhauer G, Tüting T, Immunol (Bp) 2015 Dec 1;5(4): 246- AM, Al-Shangiti AM, Al-Tawfiq JA, Hämmerling GJ, Arnold B, Oelert 255 Wikramaratna P, Alrabeeah AA, Nemere I, Garbi N, Winger Q. T. Self-Antigen Presentation by Drosten C, Memish ZA. Presence The 1,25D3 -MARRS Receptor/ Keratinocytes in the Inflamed Adult Mitschka S, Ulas T, Goller T, of Middle East respiratory syndrome PDIA3/ERp57 and Lifespan. J. Cell. Skin Modulates T Cell Auto-Reactivity. Schneider K, Egert A, Mertens J, coronavirus antibodies in Saudi Biochem. 2015 Mar 1;116(3): 380- J. Invest. Dermatol. 2015 Aug Brüstle O, Schorle H, Beyer M, Arabia: a nationwide, cross-sectional, 385 1;135(8): 1996-2004 Klee K, Xue J, Günther P, Bassler serological study. Lancet Infect Dis K, Schultze JL, Kolanus W. Co- 2015 May 1;15(5): 559-564 Nenadic I, Maitra R, Basmanav FB, Mellert F, Sinning JM, Werner N, existence of intact stemness and Schultz CC, Lorenz C, Schachtzabel Welz A, Grube E, Nickenig G, priming of neural differentiation Münch D, Engels I, Müller A, Reder- C, Smesny S, Nöthen MM, Cichon Hammerstingl C. First-in-man programs in mES cells lacking Trim71. Christ K, Falkenstein-Paul H, S, Reichenbach JR, Sauer H, transapical mitral valve replacement Sci Rep 2015 Jan 1;5(): 11126 Bierbaum G, Grein F, Bendas G, Sahl Schlösser RG, Gaser C. ZNF804A using the Direct Flow Medical® aortic HG, Schneider T. Structural variations genetic variation (rs1344706) affects valve prosthesis. Eur. Heart J. 2015 Mizushina Y, Shirasuna K, Usui F, of the cell wall precursor lipid II - brain grey but not white matter in Aug 14;36(31): 2119 Karasawa T, Kawashima A, Kimura Influence on binding and activity of the schizophrenia and healthy subjects. H, Kobayashi M, Komada T, Inoue lipoglycopeptide antibiotic oritavancin. Psychol Med 2015 Jan 1;45(1): 143- Merklinger E, Schloetel JG, Spitta L, Y, Mato N, Yamasawa H, Latz E, Antimicrob. Agents Chemother. 152 Thiele C, Lang T. No Evidence for Iwakura Y, Kasahara T, Bando M, 2015 Feb 1;59(2): 772-781 Spontaneous Lipid Transfer at ER-PM Sugiyama Y, Takahashi M. NLRP3 Netea MG, Latz E, Mills KH, O‘Neill Membrane Contact Sites. J. Membr. deficiency exacerbates hyperoxia- Münch D, Sahl HG. Structural LA. Innate immune memory: a Biol. 2015 Oct 5 induced lethality through Stat3 variations of the cell wall precursor paradigm shift in understanding host signaling independently of interleukin- lipid II in Gram-positive bacteria - defense. Nat. Immunol. 2015 Jul Meyer B, García-Bocanegra I, 1 J. Biol. Chem. 2015 Feb Impact on binding and efficacy of 1;16(7): 675-679 Wernery U, Wernery R, Sieberg A, 20;290(8): 5065-5077 antimicrobial peptides. Biochim. Müller MA, Drexler JF, Drosten C, β Biophys. Acta 2015 Nov 1;1848(11 Ng M, Ndungo E, Kaczmarek ME, Eckerle I. Serologic Assessment of Mombo IM, Berthet N, Lukashev Pt B): 3062-3071 Herbert AS, Binger T, Kuehne AI, Possibility for MERS-CoV Infection in AN, Bleicker T, Brünink S, Léger Jangra RK, Hawkins JA, Gifford RJ, Equids. Emerging Infect. Dis. 2015 L, Atencia R, Cox D, Bouchier C, Muth D, Corman VM, Meyer B, Assiri Biswas R, Demogines A, James RM, Jan 1;21(1): 181-182 Durand P, Arnathau C, Brazier L, A, Al-Masri M, Farah M, Steinhagen Yu M, Brummelkamp TR, Drosten Fair JN, Schneider BS, Drexler JF, K, Lattwein E, Al-Tawfiq JA, Albarrak C, Wang LF, Kuhn JH, Müller MA, Meyer K, Buettner S, Ghezzi D, Prugnolle F, Drosten C, Renaud F, A, Müller MA, Drosten C, Memish Dye JM, Sawyer SL, Chandran K. Zeviani M, Bano D, Nicotera P. Loss Leroy EM, Rougeron V. First Detection ZA. Infectious Middle East Respiratory Filovirus receptor NPC1 contributes to of apoptosis-inducing factor critically of an Enterovirus C99 in a Captive Syndrome Coronavirus Excretion and species-specific patterns of ebolavirus affects MIA40 function. Cell Death Chimpanzee with Acute Flaccid Serotype Variability Based on Live susceptibility in bats. Elife 2015 Jan 1 Dis 2015 Jan 1;6(): e1814 Paralysis, from the Tchimpounga Virus Isolates from Patients in Saudi Chimpanzee Rehabilitation Center, Arabia. J. Clin. Microbiol. 2015 Sep Nickenig G, Hammerstingl C. Milanez-Almeida P, Ulas T, Pasztoi Republic of Congo. PLoS ONE 2015 1;53(9): 2951-2955 The Mitralign transcatheter direct M, Glage S, Schughart K, Lutz MB, Jan 1;10(8): e0136700 mitral valve annuloplasty system. Schultze JL, Huehn J. CD11b(+) Nadorp B, Soreq H. Gut feeling: EuroIntervention 2015 Sep 1;11 Ly6C(++)Ly6G(-) Cells with Müller MA, Meyer B, Corman VM, Al- MicroRNA discriminators of the Suppl W(): W62-W63 Suppressive Activity Towards T Cells Masri M, Turkestani A, Ritz D, Sieberg intestinal TLR9-cholinergic links. Accumulate in Lungs of Influenza a A, Aldabbagh S, Bosch BJ, Lattwein Int. Immunopharmacol. 2015 Nov Nickl-Jockschat T, Stöcker T, Krug

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A, Markov V, Maximov II, Huang R, Neuropsychopharmacol 2015 Aug Oldenburg J. Optimal treatment cancer. Cell Res. 2015 Apr 1;25(4): Schneider F, Habel U, Eickhoff SB, 1;25(8): 1388-1396 strategies for hemophilia: 445-458 Zerres K, Nöthen MM, Rietschel achievements and limitations of M, Jon Shah N, Treutlein J, Kircher Nüsgen N, Goering W, Dauksa A, current prophylactic regimens. Parampalli Yajnanarayana S, Stübig T. Genetic variation in the G72 Biswas A, Jamil MA, Dimitriou I, BLOOD. 2015 Mar 26;125(13): 2038- T, Cornez I, Alchalby H, Schönberg gene is associated with increased Sharma A, Singer H, Fimmers R, 2044 K, Rudolph J, Triviai I, Wolschke C, frontotemporal fiber tract integrity. Eur Fröhlich H, Oldenburg J, Gulbinas Heine A, Brossart P, Kröger N, Wolf Arch Psychiatry Clin Neurosci 2015 A, Schulz WA, El-Maarri O. Inter-locus Østergaard SD, Mukherjee S, Sharp D. JAK1/2 inhibition impairs T cell Jun 1;265(4): 291-301 as well as intra-locus heterogeneity SJ, Proitsi P, Lotta LA, Day F, Perry function in vitro and in patients with in LINE-1 promoter methylation in JR, Boehme KL, Walter S, Kauwe myeloproliferative neoplasms. Br. J. Nielsen MJ, Lehmann J, Leeming common human cancers suggests JS, Gibbons LE, Nöthen MM, Haematol. 2015 Jun 1;169(6): 824- DJ, Schierwagen R, Klein S, Jansen selective demethylation pressure at Larson EB, Powell JF, Langenberg 833 C, Strassburg CP, Bendtsen F, specific CpGs. Clin Epigenetics 2015 C, Crane PK, Wareham NJ, Scott Møller S, Sauerbruch T, Karsdal Jan 1;7(1): 17 RA. Associations between Potentially Pas SD, Patel P, Reusken C, MA, Krag A, Trebicka J. Circulating Modifiable Risk Factors and Alzheimer Domingo C, Corman VM, Drosten Elastin Fragments Are Not Affected Oldenburg J, Lacroix-Desmazes Disease: A Mendelian Randomization C, Dijkman R, Thiel V, Nowotny by Hepatic, Renal and Hemodynamic S, Lillicrap D. Alloantibodies to Study. PLoS Med. 2015 Jun 1;12(6): N, Koopmans MP, Niedrig M. Changes, But Reflect Survival in therapeutic factor VIII in hemophilia e1001841; First international external quality Cirrhosis with TIPS. Dig. Dis. Sci. A: the role of von Willebrand factor in assessment of molecular diagnostics 2015 Nov 1;60(11): 3456-3464 regulating factor VIII immunogenicity. Otten C, De Benedetti S, Gaballah for Mers-CoV. J. Clin. Virol. 2015 Haematologica 2015 Feb 1;100(2): A, Bühl H, Klöckner A, Brauner Aug 1;69(): 81-85 Niyonzima N, Samstad EO, Aune 149-156 J, Sahl HG, Henrichfreise B. Co- MH, Ryan L, Bakke SS, Rokstad Solvents as Stabilizing Agents during Paschka P, Schlenk RF, Gaidzik AM, Wright SD, Damås JK, Mollnes Oldenburg J, Watzka M, Bevans Heterologous Overexpression in VI, Herzig JK, Aulitzky T, Bullinger TE, Latz E, Espevik T. Reconstituted CG. VKORC1 and VKORC1L1: Why Escherichia coli - Application to L, Späth D, Teleanu V, Kündgen High-Density Lipoprotein Attenuates do Vertebrates Have Two Vitamin K Chlamydial Penicillin-Binding Protein A, Köhne CH, Brossart P, Held G, Cholesterol Crystal-Induced 2,3-Epoxide Reductases? Nutrients 6. PLoS ONE 2015 Jan 1;10(4): Horst HA, Ringhoffer M, Götze K, Inflammatory Responses by Reducing 2015 Aug 1;7(8): 6250-6280 e0122110 Nachbaur D, Kindler T, Heuser M, Complement Activation. J. Immunol. Thol F, Ganser A, Döhner H, Döhner 2015 Jul 1;195(1): 257-264 Oldenburg J, Zimmermann R, Oztürk C, Schueler R, Werner N, K. ASXL1 mutations in younger adult Katsarou O, Theodossiades G, Zanon Nickenig G, Hammerstingl C. patients with acute myeloid leukemia: Nöthen (International Genomics of E, Niemann B, Kellermann E, Lundin MitraClip procedure for the treatment A study of the German-Austrian Acute Alzheimer’s Disease Consortium B. Controlled, cross-sectional MRI of a pseudo-cleft in the posterior Myeloid Leukemia Study Group. – IGAP) . Convergent genetic and evaluation of joint status in severe mitral leaflet. Eur Heart J Cardiovasc Haematologica 2015 Mar 1;100(3): expression data implicate immunity haemophilia A patients treated Imaging 2015 Jan 1;16(1): 112 324-330 in Alzheimer‘s disease. Alzheimers with prophylaxis vs. on demand. Dement 2015 Jun 1;11(6): 658-671 Haemophilia 2015 Mar 1;21(2): 171- Papadakis AI, Sun C, Knijnenburg Paternoster L, Standl M, Waage J, 179 TA, Xue Y, Grernrum W, Hölzel Baurecht H, Hotze M, [...] Novak Nozaki C, Markert A, Zimmer M, Nijkamp W, Wessels LF, N, [...] Australian Asthma Genetics A. Inhibition of FAAH reduces Oldenburg J. Hypogonadism and Beijersbergen RL, Bernards R, Huang Consortium (AAGC), [...] Nöthen nitroglycerin-induced migraine- fertility issues following primary S. SMARCE1 suppresses EGFR MM, [...] Hinds DA, Glass D, Brown like pain and trigeminal neuronal treatment for testicular cancer. Urol. expression and controls responses SJ, Heinrich J, Evans DM, Weidinger hyperactivity in mice. Eur Oncol. 2015 Sep 1;33(9): 407-412 to MET and ALK inhibitors in lung S; EArly Genetics and Lifecourse

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Epidemiology (EAGLE) Eczema Bedogni F, Branny M, Stangl K, 735-743 Dev. 2015 Sep 1;150(): 55-64 Consortium. Multi-ancestry genome- Kovac J, Schiltgen M, Kraus S, de wide association study of 21,000 Jaegere P. Optimal Implantation Pezeshkpoor B, Oldenburg J. F8 Pizarro C, Ahmadzadehfar H, cases and 95,000 controls identifies Depth and Adherence to Guidelines gene: embedded in a region of Essler M, Fimmers R, Nickenig new risk loci for atopic dermatitis. Nat. on Permanent Pacing to Improve the genomic instability representing a G, Skowasch D. Volumetric and Genet. 2015 Dec 1;47(12): 1449- Results of Transcatheter Aortic Valve hotspot of complex rearrangements. scintigraphic changes following 1456 Replacement With the Medtronic Haemophilia 2015 Jul 1;21(4): 513- endoscopic lung volume reduction. CoreValve System: The CoreValve 515 Eur. Respir. J. 2015 Jan 1;45(1): Paul F, Arkin Y, Giladi A, Jaitin DA, Prospective, International, Post- 262-265 Kenigsberg E, Keren-Shaul H, Winter Market ADVANCE-II Study. JACC Pezeshkpoor B, Theophilus D, Lara-Astiaso D, Gury M, Weiner Cardiovasc Interv 2015 May 1;8(6): BD, Guilliatt AM, Oldenburg J, Pizarro C, Ahmadzadehfar H, Essler A, David E, Cohen N, Lauridsen 837-846 Williams MD, El-Maarri O. Novel M, Tuleta I, Fimmers R, Nickenig G, FK, Haas S, Schlitzer A, Mildner A, characterization of a breakpoint in F8: Skowasch D. Effect of endobronchial Ginhoux F, Jung S, Trumpp A, Porse Peykov S, Berkel S, Degenhardt F, an individualized approach to gene valve therapy on pulmonary perfusion BT, Tanay A, Amit I. Transcriptional Rietschel M, Nöthen MM, Rappold analysis when PCR and MLPA results and ventilation distribution. PLoS Heterogeneity and Lineage GA. Rare SHANK2 variants in contradict. Haemophilia 2015 May ONE 2015 Jan 1;10(3): e0118976 Commitment in Myeloid Progenitors. schizophrenia. Mol. Psychiatry 2015 1;21(3): 392-397 Cell 2015 Dec 17;163(7): 1663-1677 Dec 1;20(12): 1487-1488 Pizarro C, Hammerstingl C, Schaefer Pflugrad H, Bronzlik P, Raab P, Tryc C, Grohé C, Nickenig G, Skowasch Pavlova A, Preisler B, Driesen J, de Peykov S, Berkel S, Schoen M, AB, Goldbecker A, Barg-Hock H, D. [New Therapeutic Approaches to Moerloose P, Zieger B, Hütker S, Weiss K, Degenhardt F, Strohmaier Strassburg CP, Ding X, Lanfermann Pulmonary Embolism: Trials‘ Results Dengler K, Harbrecht U, Oldenburg J, Weiss B, Proepper C, Schratt G, H, Weissenborn K. Cerebral white and Significance of Direct Oral J. Congenital combined deficiency Nöthen MM, Boeckers TM, Rietschel matter lesions in patients with liver Anticoagulants.] Pneumologie 2015 of coagulation factors VII and X M, Rappold GA. Identification and cirrhosis - causative for hepatic Feb 1;69(2): 99-110 - different genetic mechanisms. functional characterization of rare encephalopathy or bystanders? Liver Haemophilia 2015 May 1;21(3): 386- SHANK2 variants in schizophrenia. Int. 2015 Jul 1;35(7): 1816-1823 Pizarro C, Schaefer C, Kimeu I, Pingel 391 Mol. Psychiatry 2015 Dec 1;20(12): S, Horlbeck F, Tuleta I, Nickenig 1489-1498 Pischke S, Schwarze-Zander C, G, Skowasch D. Underdiagnosis Peng W, Novak N. Pathogenesis of Bremer B, Lehmann P, Wiegand SB, of Obstructive Sleep Apnoea atopic dermatitis. Clin. Exp. Allergy Peyrot WJ, Lee SH, Milaneschi Y, Gisa A, Behrendt P, Strassburg CP, in Peripheral Arterial Disease. 2015 Mar 1;45(3): 566-574 Abdellaoui A, Byrne EM, Esko T, de Manns MP, Wedemeyer H, Rockstroh Respiration 2015 Feb 21 Geus EJ, Hemani G, Hottenga JJ, JK. Hepatitis E Virus Seroprevalence Pennekamp PH, Strauss AC, Klein Kloiber S, Levinson DF, Lucae S, , Rate in HIV-Infected Patients in Pizarro C, Schueler R, Hammerstingl C, Marx A, Goldmann G, Friedrich Martin NG, Medland SE, Metspalu Germany: A Comparison of Two C, Tuleta I, Nickenig G, Skowasch M, Marquardt N, Oldenburg J. Giant A, Milani L, Noethen MM, Potash Commercial Assays. Intervirology D. Impact of endoscopic lung haemophilic pseudotumour of the JB, Rietschel M, Rietveld CA, Ripke 2015 Jan 1;58(5): 283-287 volume reduction on right ventricular pelvis: case report and literature S, Shi J, , Willemsen G, Zhu Z, myocardial function. PLoS ONE 2015 review. Haemophilia 2015 Nov Boomsma DI, Wray NR, Penninx Piyanova A, Lomazzo E, Bindila Jan 1;10(4): e0121377 1;21(6): e484-e486 BW. The association between L, Lerner R, Albayram O, Ruhl T, lower educational attainment and Lutz B, Zimmer A, Bilkei-Gorzo Pizarro C, Skowasch D, Nickenig G, Petronio AS, Sinning JM, Van depression owing to shared genetic A. Age-related changes in the Thomas D, Kaminski M. [Spontaneous Mieghem N, Zucchelli G, Nickenig effects? Results in ~25,000 subjects. endocannabinoid system in the rupture of aneurysmatic pulmonary G, Bekeredjian R, Bosmans J, Mol. Psychiatry 2015 Jun 1;20(6): mouse hippocampus. Mech. Ageing artery in homozygotic alpha-1-

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1;12(11): 1001 resistant Staphylococcus aureus Hu W, Dreymueller D, Liao L, Frissen Schueler R, Nickenig G, May AE, (MRSA) and Enterobacteriaceae M, Ludwig A, Gassler N, Pabst O, Schillinger W, Bekeredjian R, Ouarrak Schmid-Burgk JL, Schmidt T, expressing extended-spectrum Latz E, Sellge G, Penders J, Tacke F, T, Schofer J, Hehrlein C, Sievert H, Hornung V. Ligation-Independent ß-lactamases (ESBL-E) on a model Trautwein C. CX3CR1 is a gatekeeper Boekstegers P, Lubos E, Hoffmann Cloning (LIC) Assembly of TALEN pig farm. Appl. Environ. Microbiol. for intestinal barrier integrity in mice: R, Baldus S, Senges J, Hammerstingl Genes. Methods Mol. Biol. 2015 Jan 2015 Nov 1;81(21): 7633-7643 Limiting steatohepatitis by maintaining C. Predictors for short-term outcomes 1;1239(): 161-169 intestinal homeostasis. Hepatology of patients undergoing transcatheter Schmithausen RM, Schulze- 2015 Nov 1;62(5): 1405-1416 mitral valve interventions: analysis Schmidt R, Hofer E, Bouwman FH, Geisthoevel SV, Stemmer F, El-Jade of 778 prospective patients Buerger K, Cordonnier C, Fladby T, M, Reif M, Hack S, Meilaender A, Schönberg K, Rudolph J, Vonnahme from the German TRAMI registry Galimberti D, Georges J, Heneka Montabauer G, Fimmers R, Parcina M, Parampalli Yajnanarayana S, focusing on baseline renal function. MT, Hort J, Laczó J, Molinuevo JL, M, Hoerauf A, Exner M, Petersen Cornez I, Hejazi M, Manser AR, EuroIntervention 2015 Sep 8;11(5): O‘Brien JT, Religa D, Scheltens P, B, Bierbaum G, Bekeredjian-Ding I. Uhrberg M, Verbeek W, Koschmieder n/a Schott JM, Sorbi S. EFNS-ENS/ Analysis of Transmission of MRSA S, Brümmendorf TH, Brossart P, EAN Guideline on concomitant use and ESBL-E among Pigs and Farm Heine A, Wolf D. JAK Inhibition Schueler R, Öztürk C, Wedekind of cholinesterase inhibitors and Personnel. PLoS ONE 2015 Jan Impairs NK Cell Function in JA, Werner N, Stöckigt F, Mellert memantine in moderate to severe 1;10(9): e0138173 Myeloproliferative Neoplasms. Cancer F, Nickenig G, Hammerstingl C. Alzheimer‘s disease. Eur. J. Neurol. Res. 2015 Jun 1;75(11): 2187-2199 Persistence of Iatrogenic Atrial Septal 2015 Jun 1;22(6): 889-898 Schmitt I, Kaut O, Khazneh H, deBoni Defect After Interventional Mitral Valve L, Ahmad A, Berg D, Klein C, Fröhlich Schrage R, Schmitz AL, Gaffal E, Repair With the MitraClip System: A Schmidt T, Schmid-Burgk JL, H, Wüllner U. L-dopa increases Annala S, Kehraus S, [...]Hölzel M, Note of Caution. JACC Cardiovasc Hornung V. Synthesis of an arrayed -synuclein DNA methylation in Milligan G, Tobin AB, Gomeza J, Interv 2015 Mar 1;8(3): 450-459 sgRNA library targeting the human Parkinson‘s disease patients in vivo Dohlman HG, Sondek J, Harden genome. Sci Rep 2015 Jan 1;5(): andα in vitro. Mov. Disord. 2015 Nov TK, Bouvier M, Laporte SA, Aoki J, Schultze JL, Freeman T, Hume DA, 14987 1;30(13): 1794-1801 Fleischmann BK, Mohr K, König Latz E. A transcriptional perspective GM, Tüting T, Kostenis E. The on human macrophage biology. Schmidt-Lauber C, Bossaller L, Schmöle AC, Lundt R, Gennequin experimental power of FR900359 Semin. Immunol. 2015 Feb 1;27(1): Abujudeh HH, Vladimer GI, Christ B, Schrage H, Beins E, Krämer A, to study Gq-regulated biological 44-50 A, Fitzgerald KA, Latz E, Gravallese Zimmer T, Limmer A, Zimmer A, Otte processes. Nat Commun 2015 Jan EM, Marshak-Rothstein A, Kay J. DM. Expression Analysis of CB2-GFP 1;6(): 10156 Schultze JL, Schmieder A, Goerdt Gadolinium-based compounds induce BAC Transgenic Mice. PLoS ONE S. Macrophage activation in human NLRP3-dependent IL-1β production 2015 Jan 1;10(9): e0138986 Schuberth-Wagner C, Ludwig J, diseases. Semin. Immunol. 2015 Aug and peritoneal inflammation. Ann. Bruder AK, Herzner AM, Zillinger T, 1;27(4): 249-256 Rheum. Dis. 2015 Nov 1;74(11): Schmöle AC, Lundt R, Ternes S, Goldeck M, Schmidt T, Schmid-Burgk 2062-2069 Albayram O, Ulas T, Schultze JL, JL, Kerber R, Wolter S, Stümpel Schultze JL. Global transcriptional Bano D, Nicotera P, Alferink J, JP, Roth A, Bartok E, Drosten C, regulation in the immune system. Schmithausen RM, Kellner SR, Zimmer A. Cannabinoid receptor Coch C, Hornung V, Barchet W, Editorial. Semin. Immunol. 2015 Feb Schulze-Geisthoevel SV, Hack S, 2 deficiency results in reduced Kümmerer BM, Hartmann G, Schlee 1;27(1): 1-3 Engelhart S, Bodenstein I, Al-Sabti neuroinflammation in an Alzheimer‘s M. A Conserved Histidine in the N, Reif M, Fimmers R, Körber-Irrgang disease mouse model. Neurobiol. RNA Sensor RIG-I Controls Immune Schultze JL. Teaching ‚big data‘ B, Harlizius J, Hoerauf A, Exner M, Aging 2015 Feb 1;36(2): 710-719 Tolerance to N1-2‘O-Methylated Self analysis to young immunologists. Nat. Bierbaum G, Petersen B, Bekeredjian- RNA. Immunity 2015 Jul 21;43(1): Immunol. 2015 Sep 1;16(9): 902-905 Ding I. Eradication of methicillin- Schneider KM, Bieghs V, Heymann F, 41-51

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Schultze JL. Transcriptional Seifert R, Flick M, Bönigk W, Alvarez 1;5(): 16800 transcatheter aortic valve implantation. programming of human L, Trötschel C, Poetsch A, Müller A, EuroIntervention 2015 Feb 6 macrophages: on the way to systems Goodwin N, Pelzer P, Kashikar ND, Sharma A, Jamil MA, Nuesgen N, immunology. J. Mol. Med. 2015 Jun Kremmer E, Jikeli J, Timmermann B, Schreiner F, Priebe L, Hoffmann P, Sinning JM, Wollert KC, Sedaghat 1;93(6): 589-597 Kuhl H, Fridman D, Windler F, Kaupp Herns S, Nöthen MM, Fröhlich H, A, Widera C, Radermacher MC, UB, Strünker T. The CatSper channel Oldenburg J, Woelfle J, El-Maarri Descoups C, Hammerstingl C, Schumak B, Klocke K, Kuepper JM, controls chemosensation in sea urchin O. DNA methylation signature in Weber M, Stundl A, Ghanem A, Biswas A, Djie-Maletz A, Limmer A, sperm. EMBO J. 2015 Feb 3;34(3): peripheral blood reveals distinct Widder J, Vasa-Nicotera M, Mellert van Rooijen N, Mack M, Hoerauf A, 379-392 characteristics of human X F, Schiller W, Bauersachs J, Zur B, Dunay IR. Specific Depletion of Ly6Chi chromosome numerical aberrations. Holdenrieder S, Welz A, Grube E, Inflammatory Monocytes Prevents Seite S, Bieber T. Barrier function Clin Epigenetics 2015 Jan 1;7(1): 76 Pencina MJ, Nickenig G, Werner N, Immunopathology in Experimental and microbiotic dysbiosis in atopic Kempf T. Risk scores and biomarkers Cerebral Malaria. PLoS ONE 2015 dermatitis. Clin Cosmet Investig Shenhar-Tsarfaty S, Yayon N, for the prediction of 1-year outcome Jan 1;10(4): e0124080 Dermatol 2015 Jan 1;8(): 479-483 Waiskopf N, Shapira I, Toker S, after transcatheter aortic valve Zaltser D, Berliner S, Ritov Y, Soreq replacement. Am. Heart J. 2015 Oct Schwarze-Zander C, Pabst S, Sester DP, Sagulenko V, Thygesen H. Fear and C-reactive protein 1;170(4): 821-829 Hammerstingl C, Ohlig J, Wasmuth SJ, Cridland JA, Loi YS, Cridland cosynergize annual pulse increases in JC, Boesecke C, Stoffel-Wagner SO, Masters SL, Genske U, healthy adults. Proc. Natl. Acad. Sci. Sippel C, Kim Y, Wallau A, Brossart B, Carstensen A, Nickenig G, Hornung V, Andoniou CE, Sweet U.S.A. 2015 Feb 3;112(5): E467-E471 P, Schmidt-Wolf I, Walger P. AML Strassburg CP, Rockstroh JK, MJ, Degli-Esposti MA, Schroder K, versus ICU: outcome of septic AML Skowasch D, Schueler R. Pulmonary Stacey KJ. Deficient NLRP3 and Siebourg-Polster J, Mudrak D, patients in an intensive care setting. J. hypertension in HIV infection: a AIM2 Inflammasome Function in Emmenlauer M, Rämö P, Dehio C, Cancer Res. Clin. Oncol. 2015 Sep prospective echocardiographic study. Autoimmune NZB Mice. J. Immunol. Greber U, Fröhlich H, Beerenwinkel 1;141(9): 1645-1651 HIV Med. 2015 Oct 1;16(9): 578-582 2015 Aug 1;195(3): 1233-1241 N. NEMix: single-cell nested effects models for probabilistic pathway Sommer D, Peters AE, Baumgart AK, Sedaghat A, Al-Rashid F, Sinning Seubert B, Grünwald B, Kobuch J, stimulation. PLoS Comput. Biol. Beyer M. TALEN-mediated genome JM, Wendt D, Thielmann M, Grube Cui H, Schelter F, Schaten S, Siveke 2015 Apr 1;11(4): e1004078 engineering to generate targeted E, Nickenig G, Erbel R, Werner N, JT, Lim NH, Nagase H, Simonavicius mice. Chromosome Res. 2015 Feb Kahlert P. Outcome in TAVI patients N, Heikenwälder M, Reinheckel T, Singer H, Biswas A, Nuesgen N, 1;23(1): 43-55 with symptomatic aortic stenosis not Sleeman JP, Janssen KP, Knolle Oldenburg J, El-Maarri O. NLRP7, fulfilling PARTNER study inclusion PA, Krüger A. TIMP-1 creates a pre- Involved in Hydatidiform Molar Soreq H. Checks and balances on criteria. Catheter Cardiovasc Interv metastatic niche in the liver through Pregnancy (HYDM1), Interacts cholinergic signaling in brain and body 2015 Nov 15;86(6): 1097-1104 SDF-1/CXCR4-dependent neutrophil with the Transcriptional Repressor function. Trends Neurosci. 2015 Jul recruitment in mice. Hepatology ZBTB16. PLoS ONE 2015 Jan 1;38(7): 448-458 Sedaghat A, von Dobbeler C, Sontag 2015 Jan 1;61(1): 238-248 1;10(6): e0130416 B, Sinning JM, Fimmers R, Mellert F, Soreq L, Salomonis N, Israel Z, Schiller W, Welz A, Grube E, Nickenig Shahraz A, Kopatz J, Mathy R, Sinning JM, Hammerstingl C, Bergman H, Soreq H. Analyzing G, Hauptmann KE, Werner N. Use of Kappler J, Winter D, Kapoor S, Schueler R, Neugebauer A, Keul alternative splicing data of splice a balloon-expandable transfemoral Schütza V, Scheper T, Gieselmann S, Ghanem A, Mellert F, Schiller W, junction arrays from Parkinson sheath in a TAVI cohort with complex V, Neumann H. Anti-inflammatory Müller C, Vasa-Nicotera M, Zur B, patients‘ leukocytes before and after access site - a propensity score activity of low molecular weight Welz A, Grube E, Nickenig G, Werner deep brain stimulation as compared matched analysis. EuroIntervention polysialic acid on human N. The prognostic value of acute with control donors. Genom Data 2015 Oct 1;11(6): 698-704 macrophages. Sci Rep 2015 Jan and chronic troponin elevation after 2015 Sep 1;5(): 340-343

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Sorg UR, Behnke K, Degrandi D, apolipoprotein E-deficient mice with Orthop Unfall 2015 Oct 1;153(5): Committed Cardiomyocytes. PLoS Reich M, Keitel V, Herebian D, a high-fat diet. J Cardiol 2015 Dec 526-532 ONE 2015 Jan 1;10(8): e0135880 Deenen R, Beyer M, Schultze JL, 1;66(6): 532-538 Köhrer K, Gabbert HE, Mayatepek E, Strauss AC, Schmolders J, Friedrich Tawamie H, Wohlleber E, Uebe S, Häussinger D, Pfeffer K. Cooperative Stieber C, Grumach AS, Cordeiro MJ, Pflugmacher R, Müller MC, Schmäl C, Nöthen MM, Abou Jamra role of lymphotoxin receptor and E, Constantino-Silva RN, Barth S, Goldmann G, Oldenburg J, R. Recurrent null mutation in SPG20 tumor necrosis factor receptor p55 in Hoffmann P, Pesquero JB, Renné T, Pennekamp PH. Outcome after total leads to Troyer syndrome. Mol. Cell. murine liver regeneration.β J. Hepatol. Nöthen MM, Cichon S. First report knee arthroplasty in haemophilic Probes 2015 Oct 1;29(5): 315-318 2015 Dec 19 of a FXII gene mutation in a Brazilian patients with stiff knees. Haemophilia family with hereditary angio-oedema 2015 Jul 1;21(4): e300-e305 Terhal PA, Nievelstein RJ, Verver EJ, Stanton MC, Mkwanda SZ, Debrah with normal C1 inhibitor. Br. J. Topsakal V, van Dommelen P, [...] AY, Batsa L, Biritwum NK, Hoerauf Dermatol. 2015 Oct 1;173(4): 1102- Strünker T, Alvarez L, Kaupp UB. At Betz RC,[...]w Vreeburg M, Wakeling A, Cliffe M, Best A, Molineux A, Kelly- 1104 the physical limit - chemosensation in E, Knoers NV, Coucke P, Mortier Hope LA. Developing a community- sperm. Curr. Opin. Neurobiol. 2015 GR. A study of the clinical and led SMS reporting tool for the rapid Stiess M, Wegehingel S, Nguyen C, Oct 1;34(): 110-116 radiological features in a cohort of assessment of lymphatic filariasis Nickel W, Bradke F, Cambridge SB. 93 patients with a COL2A1 mutation morbidity burden: case studies from A Dual SILAC Proteomic Labeling Strünker T, Kaupp UB. Larry causing spondyloepiphyseal dysplasia Malawi and Ghana. BMC Infect. Dis. Strategy for Quantifying Constitutive Cohen-50 ways to DYE your science. congenita or a related phenotype. 2015 Jan 1;15(): 214 and Cell-Cell Induced Protein Neurophotonics 2015 Apr 1;2(2): Am. J. Med. Genet. A 2015 Mar Secretion. J. Proteome Res. 2015 021004 1;167A(3): 461-475 Staudacher A, Hinz T, Novak N, von Aug 7;14(8): 3229-3238 Bubnoff D, Bieber T. Exaggerated Stuart PE, Nair RP, Tsoi LC, Tejasvi Thomas A, Biswas A, Ivaskevicius IDO1 expression and activity in Stingl JC, Welker S, Hartmann G, T, Das S, [...] Nöthen MM, [...] V, Oldenburg J. Structural and Langerhans cells from patients Damann V, Gerzer R. Where Failure Is Gregersen PK, Franke A, Gladman functional influences of coagulation with atopic dermatitis upon viral Not an Option -Personalized Medicine DD, Abecasis GR, Elder JT. Genome- factor XIII subunit B heterozygous stimulation: a potential predictive in Astronauts. PLoS ONE 2015 Jan wide Association Analysis of Psoriatic missense mutants. Mol Genet biomarker for high risk of Eczema 1;10(10): e0140764 Arthritis and Cutaneous Psoriasis Genomic Med 2015 Jul 1;3(4): 258- herpeticum. Allergy 2015 Nov Reveals Differences in Their Genetic 271 1;70(11): 1432-1439 Stöckigt F, Jüngst P, Linhart M, Architecture. Am. J. Hum. Genet. Nickenig G, Andrié R, Beiert T, 2015 Dec 3;97(6): 816-836 Thor T, Künkele A, Pajtler KW, Stein A, Stroobants S, Gieselmann Schrickel JW. Association of Heart Wefers AK, Stephan H, [...] Zimmer V, D‘Hooge R, Matzner U. Rate Turbulence With Arrhythmia Sturm M, Becker A, Schroeder A, A, [...] Schüller U, de Angelis MH, Anti-inflammatory Therapy Susceptibility and Heart Disease in Bilkei-Gorzo A, Zimmer A. Impact of Eggert A, Schramm A, Schulte JH. With Simvastatin Improves Mice. J. Cardiovasc. Electrophysiol. chronic corticosterone application on MiR-34a deficiency accelerates Neuroinflammation and CNS Function 2015 Jul 29 depression-like behavior in C57BL/6N medulloblastoma formation in vivo. in a Mouse Model of Metachromatic and C57BL/6J mice. Genes Brain Int. J. Cancer 2015 May 15;136(10): Leukodystrophy. Mol. Ther. 2015 Jul Strauss AC, Goldmann G, Behav. 2015 Mar 1;14(3): 292-300 2293-2303 1;23(7): 1160-1168 Schmolders J, Müller MC, Placzek R, Oldenburg J, Wirtz DC, Pennekamp Tarnawski L, Xian X, Monnerat G, Tiede A, Oldenburg J, Lissitchkov T, Steinmetz M, Lucanus E, Zimmer S, PH. [Impact of Preoperative Knee Macaulay IC, Malan D, Borgman A, Knaub S, Bichler J, Manco-Johnson Nickenig G, Werner N. Mobilization Stiffness on the Postoperative Wu SM, Fleischmann BK, Jovinge MJ. Prophylaxis vs. on-demand of sca1/flk-1 positive endothelial Outcome after Total Knee Arthroplasty S. Integrin Based Isolation Enables treatment with Nuwiq(®) (Human- progenitor cells declines in in Patients with Haemophilia]. Z Purification of Murine Lineage cl rhFVIII) in adults with severe

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haemophilia A. Haemophilia 2015 polyadenylation element binding 1;8(2): 327-333 Oldenburg J, Dreßen P, Brettner Nov 19 (CPEB)2 protein expression and its S, Homann J, Molderings GJ. RNA binding activity. Hippocampus Vijayakrishnan J, Henrion M, Determination of plasma heparin level Tiyerili V, Becher UM, Camara B, 2015 May 1;25(5): 630-642 Moorman AV, Fiege B, Kumar R, improves identification of systemic Yildirimtürk C, Aksoy A, Kebschull [...] Nöthen MM,[...] Greaves M, mast cell activation disease. PLoS M, Werner N, Nickenig G, Müller C. Uschner FE, Ranabhat G, Choi SS, Hemminki K, Harrison CJ, Stanulla ONE 2015 Jan 1;10(4): e0124912 Impact of peroxisome proliferator- Granzow M, Klein S, Schierwagen M, Houlston RS. The 9p21.3 risk activated receptor on angiotensin R, Raskopf E, Gautsch S, van der of childhood acute lymphoblastic Walenbergh SM, Houben T, Hendrikx II type 1 receptor-mediated insulin Ven PF, Fürst DO, Strassburg CP, leukaemia is explained by a rare high- T, Jeurissen ML, van Gorp PJ, Vaes sensitivity, vascularγ inflammation and Sauerbruch T, Diehl AM, Trebicka impact variant in CDKN2A. Sci Rep N, Olde Damink SW, Verheyen F, atherogenesis in hypercholesterolemic J. Statins activate the canonical 2015 Jan 1;5(): 15065 Koek GH, Lütjohann D, Grebe A, Latz mice. Arch Med Sci 2015 Aug hedgehog-signaling and aggravate E, Shiri-Sverdlov R. Weekly Treatment 12;11(4): 877-885 non-cirrhotic portal hypertension, but Vilz TO, Roessel L, Chang J, Pantelis of 2-Hydroxypropyl- -cyclodextrin inhibit the non-canonical hedgehog D, Schwandt T, Koscielny A, Wehner Improves Intracellular Cholesterol Tiyerili V, Nickenig G, Hammerstingl signaling and cirrhotic portal S, Kalff JC. Establishing a biomarker Levels in LDL Receptorβ Knockout C. Catch of the day: interventional hypertension. Sci Rep 2015 Jan 1;5(): for postoperative ileus in humans - Mice. Int J Mol Sci 2015 Jan 1;16(9): device retrieval after late embolization 14573 Results of the BiPOI trial. Life Sci. 21056-21069 of an Amplatzer cardiac plug left 2015 Dec 15;143(): 58-64 atrial appendage occluder. Clin Res Vacchelli E, Ma Y, Baracco EE, Sistigu Wali A, Liu L, Takeichi T, Jelani M, Cardiol 2015 Dec 1;104(12): 1106- A, Enot DP, [...] Schultze JL,[...] Vitale Vogt CC, Bruegmann T, Malan D, Rahman OU, Heng YK, Thng S, Lee 1108 I, Laurent-Puig P, Mattei F, Zitvogel L, Ottersbach A, Roell W, Fleischmann J, Akiyama M, McGrath JA, Betz RC. Kroemer G. Chemotherapy-induced BK, Sasse P. Systemic gene transfer Familial Primary Localized Cutaneous Traschütz A, Tzaridis T, Penner AH, antitumor immunity requires formyl enables optogenetic pacing of mouse Amyloidosis Results from Either Kuchelmeister K, Urbach H, Hattingen peptide receptor 1. Science 2015 hearts. Cardiovasc. Res. 2015 May Dominant or Recessive Mutations in E, Heneka MT. Reduction of Nov 20;350(6263): 972-978 1;106(2): 338-343 OSMR. Acta Derm. Venereol. 2015 microbleeds by immunosuppression Nov 1;95(8): 1005-1007 in a patient with A -related vascular Vaitsiakhovich T, Drichel D, Herold Vollbach S, Müller A, Drexler JF, inflammation. Neurol Neuroimmunol C, Lacour A, Becker T. METAINTER: Simon A, Drosten C, Eis-Hübinger Walker M, Specht S, Churcher TS, Neuroinflamm 2015β Dec 1;2(6): e165 meta-analysis of multiple regression AM, Panning M. Prevalence, type and Hoerauf A, Taylor MJ, Basáñez models in genome-wide association concentration of human enterovirus MG. Therapeutic Efficacy and Tuleta I, Reek D, Braun P, Bauriedel studies. Bioinformatics 2015 Jan and parechovirus in cerebrospinal fluid Macrofilaricidal Activity of Doxycycline G, Nickenig G, Skowasch D, Andrié 15;31(2): 151-157 samples of pediatric patients over a for the Treatment of River Blindness. R. Influence of intimal Chlamydophila 10-year period: a retrospective study. Clin. Infect. Dis. 2015 Apr 15;60(8): pneumoniae persistence on van Setten J, Išgum I, Pechlivanis S, Virol. J. 2015 Jan 1;12(): 199 1199-1207 cardiovascular complications after Tragante V, de Jong PA, Smolonska coronary intervention. Infection 2015 J, Platteel M, Hoffmann P, Oudkerk von Websky MW, Kalff JC, Schäfer Wasserman E, Tam J, Mechoulam Feb 1;43(1): 51-57 M, de Koning HJ, Nöthen MM, N. Current knowledge on regulation R, Zimmer A, Maor G, Bab I. Moebus S, Erbel R, Jöckel KH, and impairment of motility after CB1 cannabinoid receptors Turimella SL, Bedner P, Skubal M, Viergever MA, Mali WP, de Bakker PI. intestinal transplantation. Curr Opin mediate endochondral skeletal Vangoor VR, Kaczmarczyk L, Karl Serum Lipid Levels, Body Mass Index, Organ Transplant 2015 Jun 1;20(3): growth attenuation by Δ9- K, Zoidl G, Gieselmann V, Seifert and Their Role in Coronary Artery 303-307 tetrahydrocannabinol. Ann. N. Y. G, Steinhäuser C, Kandel E, Theis Calcification: A Polygenic Analysis. Acad. Sci. 2015 Jan 1;1335(): 110- M. Characterization of cytoplasmic Circ Cardiovasc Genet 2015 Apr Vysniauskaite M, Hertfelder HJ, 119

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Wassermann R, Gulen MF, Sala C, R, Hose D, Hemminki K. The 7p15.3 Is there a risk of filarial infection during F, Herms J, Konnerth A, Marie H, Perin SG, Lou Y, Rybniker J, Schmid- (rs4487645) association for multiple long-term missions in Haiti? Travel Haass C. -Secretase processing Burgk JL, Schmidt T, Hornung V, myeloma shows strong allele-specific Med Infect Dis 2015 Dec 19 of APP inhibits neuronal activity in Cole ST, Ablasser A. Mycobacterium regulation of the MYC-interacting the hippocampus.η Nature 2015 Oct tuberculosis Differentially Activates gene CDCA7L in malignant plasma Wenzel M, Senges CH, Zhang J, 15;526(7573): 443-447 cGAS- and Inflammasome-Dependent cells. Haematologica 2015 Mar Suleman S, Nguyen M, Kumar P, Intracellular Immune Responses 1;100(3): e110-e113 Chiriac AI, Stepanek JJ, Raatschen Wilsmann-Theis D, Wagenpfeil through ESX-1. Cell Host Microbe N, May C, Krämer U, Sahl HG, J, Holzinger D, Roth J, Koch S, 2015 Jun 10;17(6): 799-810 Weis M, Behner L, Binger T, Drexler Straus SK, Bandow JE. Antimicrobial Schnautz S, Bieber T, Wenzel J. JF, Drosten C, Maisner A. Fusion Peptides from the Aurein Family Form Among the S100 proteins, S100A12 Weber M, Brüggemann E, Schueler R, activity of African henipavirus F Ion-Selective Pores in Bacillus subtilis. is the most significant marker for Momcilovic D, Sinning JM, Ghanem proteins with a naturally occurring Chembiochem 2015 May 4;16(7): psoriasis disease activity. J Eur Acad A, Werner N, Grube E, Schiller start codon directly upstream of the 1101-1108 Dermatol Venereol 2015 Sep 2 W, Mellert F, Welz A, Nickenig signal peptide. Virus Res. 2015 Apr G, Hammerstingl C. Impact of left 2;201(): 85-93 Wernery U, Corman VM, Wong Witkowski PT, Kallies R, Hoveka J, ventricular conduction defect with EY, Tsang AK, Muth D, Lau SK, Auste B, Ithete NL, Šoltys K, Szemes or without need for permanent right Weisheit CK, Engel DR, Kurts C. Khazanehdari K, Zirkel F, Ali M, Nagy T, Drosten C, Preiser W, Klempa ventricular pacing on functional and Dendritic Cells and Macrophages: P, Juhasz J, Wernery R, Joseph S, B, Mfune JK, Kruger DH. Novel clinical recovery after TAVR. Clin Res Sentinels in the Kidney. Clin J Am Syriac G, Elizabeth SK, Patteril NA, Arenavirus Isolates from Namaqua Cardiol 2015 Nov 1;104(11): 964-974 Soc Nephrol 2015 Oct 7;10(10): Woo PC, Drosten C. Acute middle Rock Mice, Namibia, Southern Africa. 1841-1851 East respiratory syndrome coronavirus Emerging Infect. Dis. 2015 Jul Weber M, Sediri H, Felgenhauer U, infection in livestock Dromedaries, 1;21(7): 1213-1216 Binzen I, Bänfer S, Jacob R, Brunotte Weismüller TJ, Lerch C, Evangelidou Dubai, 2014. Emerging Infect. Dis. L, García-Sastre A, Schmid-Burgk E, Strassburg CP, Lehner F, 2015 Jun 1;21(6): 1019-1022 Witt A, Seeger JM, Coutelle O, JL, Schmidt T, Hornung V, Kochs G, Schrem H, Klempnauer J, Manns Zigrino P, Broxtermann P, Andree M, Schwemmle M, Klenk HD, Weber F. MP, Haller H, Schiffer M. A pocket Wiencierz AM, Kernbach M, Ecklebe Brinkmann K, Jüngst C, Schauss AC, Influenza Virus Adaptation PB2-627K guide to identify patients at risk for J, Monnerat G, Tomiuk S, Raulf A, Schüll S, Wohlleber D, Knolle PA, Modulates Nucleocapsid Inhibition by chronic kidney disease after liver Christalla P, Malan D, Hesse M, Krönke M, Mauch C, Kashkar H. IAP the Pathogen Sensor RIG-I. Cell Host transplantation. Transpl. Int. 2015 Bosio A, Fleischmann BK, Eckardt antagonization promotes inflammatory Microbe 2015 Mar 11;17(3): 309-319 May 1;28(5): 519-528 D. Differential Expression Levels destruction of vascular endothelium. of Integrin 6 Enable the Selective EMBO Rep. 2015 Jun 1;16(6): 719- Weighardt H, Förster I. Bcl-3 puts the Weisser-Thomas J, Kempelmann Identification and Isolation of Atrial and 727 brakes on contact hypersensitivity. H, Nickenig G, Grohe C, Djoufack Ventricular αCardiomyocytes. PLoS Eur. J. Immunol. 2015 Apr 1;45(4): P, Fink K, Meyer R. Influence of ONE 2015 Jan 1;10(11): e0143538 Wittmann S, Behrendt R, Eissmann 971-974 gelsolin deficiency on excitation K, Volkmann B, Thomas D, Ebert contraction coupling in adult Willem M, Tahirovic S, Busche MA, T, Cribier A, Benkirane M, Hornung Weinhold N, Meissner T, Johnson murine cardiomyocytes. J. Physiol. Ovsepian SV, Chafai M, Kootar V, Bouzas NF, Gramberg T. DC, Seckinger A, Moreaux J, Försti A, Pharmacol. 2015 Jun 1;66(3): 373- S, Hornburg D, Evans LD, Moore Phosphorylation of murine SAMHD1 Chen B, Nickel J, Chubb D, Rawstron 383 S, Daria A, Hampel H, Müller V, regulates its antiretroviral activity. AC, Doughty C, Dahir NB, Begum Giudici C, Nuscher B, Wenninger- Retrovirology 2015 Jan 1;12(): 103 DB, Young K, Walker BA, Hoffmann Weitzel T, Rosas R, Fica A, Dabanch Weinzierl A, Kremmer E, Heneka P, Nöthen MM, Davies FE, Klein B, J, Polanco M, Egaña A, Triantafilo V, MT, Thal DR, Giedraitis V, Lannfelt Wolter F, Glässner A, Krämer Goldschmidt H, Morgan GJ, Houlston Pfarr K, Hoerauf A, Reiter-Owona I. L, Müller U, Livesey FJ, Meissner B, Kokordelis P, Finnemann C,

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Kaczmarek DJ, Goeser F, Lutz P, Barré-Sinoussi F, Delfraissy JF, Zoulim Nischalke HD, Strassburg CP, F. Towards an HBV cure: state-of-the- Spengler U, Nattermann J. Hypoxia art and unresolved questions-report impairs anti-viral activity of natural of the ANRS workshop on HBV cure. killer (NK) cells but has little effect Gut 2015 Aug 1;64(8): 1314-1326 on anti-fibrotic NK cell functions in hepatitis C virus infection. J. Hepatol. Zeitler H, Balta Z, Klein B, Strassburg 2015 Dec 1;63(6): 1334-1344 CP. Extracorporeal Treatment in Severe Hypertriglyceridemia-Induced Yakut E, Jakobs C, Peric A, Michel G, Pancreatitis. Ther Apher Dial 2015 Baal N, Bein G, Brüne B, Hornung Aug 1;19(4): 405-410 V, Hackstein H. Extracorporeal Photopheresis Promotes IL-1 Zimmer A. Genetic Manipulation of Production. J. Immunol. 2015 Mar the Endocannabinoid System. Handb 15;194(6): 2569-2577 β Exp Pharmacol 2015 Jan 1;231(): 129-183 Yao H, Dittmann M, Peisley A, Hoffmann HH, Gilmore RH, Schmidt Zimmer S, Grebe A, Latz E. Danger T, Schmid-Burgk JL, Hornung V, Rice Signaling in Atherosclerosis. Circ. CM, Hur S. ATP-Dependent Effector- Res. 2015 Jan 16;116(2): 323-340 like Functions of RIG-I-like Receptors. Mol. Cell 2015 May 7;58(3): 541-548 Zuern CS, Bauer A, Lubos E, Boekstegers P, Puls M, Bardeleben Zehner M, Burgdorf S. Sec61 RS, Ouarrak T, Butter C, Eggebrecht in antigen cross-presentation. H, Nickenig G, Zahn R, Senges J, Oncotarget 2015 Jun 22 May AE. Influence of non-cardiac comorbidities on outcome after Zehner M, Marschall AL, Bos E, percutaneous mitral valve repair: Schloetel JG, Kreer C, Fehrenschild results from the German transcatheter D, Limmer A, Ossendorp F, Lang T, mitral valve interventions (TRAMI) Koster AJ, Dübel S, Burgdorf S. The registry. Clin Res Cardiol 2015 Dec translocon protein sec61 mediates 1;104(12): 1044-1053 Model of the BMZ II, University Hospital Bonn antigen transport from endosomes in by Ludes Generalplaner GmbH the cytosol for cross-presentation to CD8(+) T cells. Immunity 2015 May 19;42(5): 850-863

Zeisel MB, Lucifora J, Mason WS, Sureau C, Beck J, Levrero M, Kann M, Knolle PA, Benkirane M, Durantel D, Michel ML, Autran B, Cosset FL, Strick-Marchand H, Trépo C, Kao JH, Carrat F, Lacombe K, Schinazi RF,

150 151 Prizes and Distinctions awarded within Prizes & Distinctions ImmunoSensation 2015

2015 Prof. Frank Bradke has been awarded the Gottfried Wilhelm Leibniz prize. Cluster member Prof. Bradke is the head of the “Axon Growth and Regeneration” research group at the German Center for Neurodegenerative Diseases (DZNE). The award includes prize money of 2,5 million €.

2015 Prof. Veit Hornung from the Institute of Molecular Medicine, University Hos- pital Bonn has been announced by EMBO as one of 58 outstanding researchers in the field of life sciences that have been elected to its membership.

2015 Prof. Veit Hornung received ERC (European Research Council) Consolidator Grant for his project “Genetic Dissection of Innate Immune Sensing and Signal- ing” (GENESIS).

2015 Prof. Thomas Tüting (Department of Dermatology) received the Photoder- matology Research Award. This international award is being sponsored by La Roche-Posay Laboratoire Pharma- ceutique Germany. The prize is awarded biennially.

February 2015 Prof. Achim Hörauf and his research team (Institute of Medical Microbiology, Immunology and Parasitology at the University Hospital Bonn) has been awarded the “Memento Preis für vernachlässigte Krankheiten” 2015. The award was launched by Ärzte ohne Grenzen e.V., Brot für die Welt, DAHW Deut- sche Lepra, Tuberkulosehilfe e.V. and BUKO Pharma-Kampagne in 2014. The Memen- to Preis is awarded annually. This year the prize giving ceremony took place in Berlin on February 25, 2015.

February 2015 Prof. Hermona Soreq (Hebrew University) received the “Rappaport Prize” for her Excellence in Medical Research. The Rappaport family established the prize in order to promote visionary, groundbreak- ing and innovative research with therapeutic ramifications that significantly promote human health. Cluster member Hermona Soreq received $60,000 for her research on the neurotransmitter acetylcholine’s role in both health and disease in the brain and other organs.

March 23, 2015 Prof. Waldemar Kolanus was elected as executive Director of the LIMES Institute. ImmunoSensation’s vice speaker Prof. Waldemar Kolanus was officially elected as the new executive Director of the LIMES Institute.

April 2015 Prof. Achim Hörauf has been awarded the BioRegionen Innovation Prize of 2015. Cluster member Prof. Achim Hörauf (Institute of Medical Microbiology, Immunology & Parasitology, University Hospital Bonn) and his team received the BioRegionen Innova- tion Prize 2015 for their remarkable invention in the field of tropical infectious diseases.

153 Prizes and Distinctions awarded within ImmunoSensation 2015

April 29, 2015 Inauguration of Cluster member Prof. Michael Hoch as rector of the University of Bonn. The former excecutive Director of the LIMES Institute is the 143. rector of the Rhein- sche Friedrich-Wilhelms-Universtität Bonn.

May 2015 Prof. Christian Kurts from the Institute of Experimental Immunology, University Hospital Bonn became an elected member of the German National Academy of Sciences, Leopoldina.

September 30 - October 03, 2015 Dr. Anna-Maria Herzner received the Paula Pitha Award. Anna-Maria Herzner from the Institute of Clinical Chemistry and Clinical Pharmacolo- gy received the Paula Pitha Award for the Best Abstract on Interferon Research at the TOLL2015 Conference (http://www.toll2015.org), which took place in Marbella, Spain. More than 400 abstracts had been submitted.

October 30, 2015 Dr. Beate Henrichfreise has been awarded the PHOENIX Phar- mazie Wissenschaftspreis. The prize is being awarded in the categories pharmacology and clinical pharmacy, pharmaceutical biology, pharmaceutical chemistry and pharmaceutical technology. Beate Henrichfreise from the Insitute of Medical Microbiology, Immunology & Parasi- tology, University of Bonn received the prize in the field “pharmaceutical biology” with her publication “AmiA is a penicillin target enzyme with dual activity in the intracellular pathogen Chlamydia pneumoniae” (Nature Communications. 5, 4201, 2014).

November 2015 Dr. Annkristin Heine received the Lisec-Artz award. Cluster member Dr. Annkristin Heine from the Medical Clinic III and Institute of Experi- mental Immunology received the Lisec-Artz award for her outstanding cancer research.

November 2015 Prof. Christian Kurts is speaker of the DFG funded Bonn and Melbourne International Research and Training Group (Bo&MeRanG) that will start in April 2016 and covers the topic „Myeloid Antigen Presenting Cells and the Induction of Adaptive Immunity”.

November 27, 2015 DFG Review Board Election 2015. Inauguration of Prof. Michael Hoch as rector of the University of Bonn Three Cluster members have been elected as members of the DFG review boards for by Volker Lannert the 2016-2019 term. The DFG review boards scientifically evaluate proposal to fund research projects in their respective subject areas. The following ImmunoSensation members have been elected: Prof. Achim Hörauf (Institute of Medical Microbiology, Immunology & Parasitology, University Hospital Bonn) for subject area Medical Microbiology, Parasitology, Medical Mycology, and Hygiene, Molecular Infection Biology, Prof. Irmgard Förster (LIMES Institute, University of Bonn) for the subject area Immunology, Prof. Christian Kurts (Institute of Experimental Immu- nology, University Hospital Bonn) for the subject area Nephrology.

154 155 Annual Report 2015 Members ImmunoSensation Member List

Abdullah, Zeinab Institute of Experimental Immunology Medical Faculty, University of Bonn, University Hospital Bonn [email protected]

Al-Amoudi, Ashraf German Centre for Neurodegenerative Diseases (DZNE) [email protected]

Bano, Daniele German Centre for Neurodegenerative Diseases (DZNE) [email protected]

Barchet, Winfried Institute of Clinical Chemistry and Clinical Pharmacology Medical Faculty, University of Bonn, University Hospital Bonn [email protected]

Becker, Tim German Centre for Neurodegenerative Diseases (DZNE) [email protected]

Betz, Regina Institute of Human Genetics Medical Faculty, University of Bonn, University Hospital Bonn [email protected]

Beyer, Marc Life & Medical Sciences Institute (LIMES) Mathematics and Natural Sciences Faculty, University of Bonn [email protected]

Bieber, Thomas Department of Dermatology & Allergology Medical Faculty, University of Bonn, University Hospital Bonn [email protected]

Bovier, Anton Probability Theory and Stochastic Analysis Institute for Applied Mathematics, Mathematics and Natural Sciences Faculty University of Bonn [email protected]

Bradke, Frank German Centre for Neurodegenerative Diseases (DZNE) [email protected]

157 Annual Report 2015 Annual Report 2015 ImmunoSensation Member List ImmunoSensation Member List

Brossart, Peter Gerzer, Rupert Medical Clinic III for Hematology and Oncology Institute of Aerospace Medicine Medical Faculty, University of Bonn, University Hospital Bonn German Aerospace Center (DLR), Cologne [email protected] [email protected]

Burgdorf, Sven Geyer, Matthias Life & Medical Sciences Institute (LIMES) Institute of Innate Immunity Mathematics and Natural Sciences Faculty, University of Bonn Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

Dilloo, Dagmar Gieselmann, Volkmar Department of Pediatric Haematology & Oncology Institute of Biochemistry & Molecular Biology Medical Faculty, University of Bonn, University Hospital Bonn Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

Drosten, Christian Halle, Annett Institute of Virology center of advanced european studies and research (caesar) Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected] Hartmann, Gunther Fava, Eugenio Institute of Clinical Chemistry & Clinical Pharmacology German Center for Neurodegenerative Diseases (DZNE) Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

Fleischmann, Bernd K. Heine, Annkristin Institut für Physiologie 1 Medical Clinic III & Institute of Experimental Immunology Medical Faculty, University of Bonn, University Hospital Bonn Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

Förster, Irmgard Heneka, Michael Life & Medical Sciences Institute (LIMES) Institute of Neurology Mathematics and Natural Sciences Faculty, University of Bonn Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

Fröhlich, Holger Hoch, Michael Algorithmic Bioinformatics at the B-IT Life & Medical Sciences Institute (LIMES) Mathematics and Natural Sciences Faculty, University of Bonn Mathematics and Natural Sciences Faculty, University of Bonn [email protected] [email protected]

Garbi, Natalio Hölzel, Michael Institute of Experimental Immunology Institute of Clinical Chemistry & Clinical Pharmacology Medical Faculty, University of Bonn, University Hospital Bonn Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

158 159 Annual Report 2015 Annual Report 2015 ImmunoSensation Member List ImmunoSensation Member List

Hörauf, Achim Latz, Eicke Institute of Medical Microbiology, Immunology and Parasitology Institute of Innate Immunity Medical Faculty, University of Bonn, University Hospital Bonn Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

Hornung, Veit Neumann, Harald Institute of Molecular Medicine Institute of Reconstructive Neurobiology Medical Faculty, University of Bonn, University Hospital Bonn Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

Kalff, Jörg Nickenig, Georg Department of Surgery Medical Clinic II for Cardiology, Angiology and Pneumology Medical Faculty, University of Bonn, University Hospital Bonn Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

Kastenmüller, Wolfgang Nicotera, Pierluigi Institute of Experimental Immunology German Center for Neurodegenerative Diseases (DZNE) Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected] Nöthen, Markus M. Kaupp, U. Benjamin Institute of Human Genetics center of advanced european studies and research (caesar) Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

Knolle, Percy Novak, Natalija Institutes of Molecular Immunology and Experimental Oncology Department of Dermatology Klinikum München rechts an der Isar, TU München Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

Kolanus, Waldemar Oldenburg, Johannes Life & Medical Sciences Institute (LIMES) Experimental Haematology and Transfusion Medicine Mathematics and Natural Sciences Faculty, University of Bonn Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

Kurts, Christian Pankratz, Michael J. Institute of Experimental Immunology Life & Medical Sciences Institute (LIMES) Medical Faculty, University of Bonn, University Hospital Bonn Mathematics and Natural Sciences Faculty, University of Bonn [email protected] [email protected]

Lange, Christoph Sahl, Hans-Georg Institute of Genomic Mathematics Institute of Medical Microbiology, Immunology and Parasitology Medical Faculty, University of Bonn, University Hospital Bonn Medical Faculty, University of Bonn, University Hospital Bonn [email protected] [email protected]

160 161 Annual Report 2015 Annual Report 2015 ImmunoSensation Member List ImmunoSensation Member List

Wehner, Sven Department of Surgery Schlee, Martin Medical Faculty, University of Bonn, University Hospital Bonn Institute of Clinical Chemistry & Clinical Pharmacology [email protected] Medical Faculty, University of Bonn, University Hospital Bonn [email protected] Wilhelm, Christoph Institute of Clinical Chemistry & Clinical Pharmacology Schlitzer, Andreas Medical Faculty, University of Bonn, University Hospital Bonn Life & Medical Sciences Institute (LIMES) [email protected] Mathematics and Natural Sciences Faculty, University of Bonn [email protected] Zimmer, Andreas Institute of Molecular Psychiatry Schultze, Joachim Medical Faculty, University of Bonn, University Hospital Bonn Life & Medical Sciences Institute (LIMES) [email protected] Mathematics and Natural Sciences Faculty, University of Bonn [email protected]

Soreq, Hermona Department of Biological Chemistry Hebrew University, Jerusalem, Israel [email protected]

Spengler, Ulrich Medical Clinic I - General Internal Medicine Medical Faculty, University of Bonn, University Hospital Bonn [email protected]

Strassburg, Christian Medical Clinic I - General Internal Medicine Medical Faculty, University of Bonn, University Hospital Bonn [email protected]

Thiele, Christoph Life & Medical Sciences Institute (LIMES) Mathematics and Natural Sciences Faculty, University of Bonn [email protected]

Tüting, Thomas Department of Dermatology Medical Faculty, University of Bonn, University Hospital Bonn [email protected]

Wachten, Dagmar Turtles at the Poppelsdorfer Schloss University of Bonn center of advanced european studies and research (caesar) by Dr. Thomas Mauersberg [email protected]

162 163 10 Most Relevant Publications for Dr. Zeinab Abdullah 1. Beyer M. *, Abdullah Z. *, Chemnitz J. M. *, M. Daniela, Dr. Zeinab Abdullah, PhD Sander J., Lehmann C., Thabet Y., Shinde, P. V., Schmidle- Institute of Experimental Immunology ithner L., Köhne M., Trebicka J., Schierwagen R., Hofmann A. Popov A., Lang K. S., Oxenius A., Buch T., Kurts C., Heiken- Biosketches wälder M., Fätkenheuer G., Lang P. A., Hartmann P., Knolle P. A. *, Schultze J. L. *. (2016). TNF impairs CD4+ T-cell mediat- new Member since 2015 ed immune control in chronic viral infection. Nat Immunology 2. Hasenberg, A., Hasenberg, M., Mann, L., Neumann, F., Borkenstein, L., Stecher, M., Kraus, A., Engel, D. R., Klingberg, New Members A., Seddigh, P., Abdullah, Z., Klebow, S., Engelmann, S., Re- inhold, A., Brandau, S., Seeling, M., Waisman, A., Schraven, B., Gothert, J. R., Nimmerjahn, F., Gunzer, M. (2015): Catchup: a mouse model for imaging-based tracking and modulation of neutrophil granulocytes. Nat Methods 12, 445-452. 3. Bottcher, J. P., Beyer, M., Meissner, F., Abdullah, Z., Sander, J., Hochst, B., Eickhoff, S., Rieckmann, J. C., Russo, C., Bauer, T., Flecken, T., Giesen, D., Engel, D., Jung, S., Busch, D. H., Protzer, U., Thimme, R., Mann, M., Kurts, C., Schultze, J. L., Kastenmuller, W., Knolle, P. A. (2015): Func- tional classification of memory CD8(+) T cells by CX3CR1 expression. Nat Commun 6, 8306. Rheinische Friedrich-Wilhelms-Universität Bonn 4. M. J. Wolf, Adili, A., Piotrowitz, K., Abdullah, Z., Boege, Institute of Experimental Immunology Y., Stemmer, K., Ringelhan, M., Simonavicius, N., Egger, M., E-Mail: [email protected] Wohlleber, D., Lorentzen, A., Einer, C., Schulz, S., Clavel, T., Protzer, U., Thiele, C., Zischka, H., Moch, H., Tschop, M., Research Expertise Tumanov, A. V., Haller, D., Unger, K., Karin, M., Kopf, M., The overall goal of our research is to understand the mo- Knolle, P., Weber, A. and Heikenwalder, M. (2014): Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes lecular and cellular mechanisms by which chronic inflam- nonalcoholic steatohepatitis and liver cancer via cross-talk with mation can affect outcome of infection and immune cell hepatocytes. Cancer cell, 549-64 function. Specifically, the research focuses on mechanistic 5. Abdullah, Z. and Knolle, P. A. (2014): Scaling of immune studies to understand the impact of chronic inflammation responses against intracellular bacterial infection. The EMBO during liver fibrosis on the function of hepatic myeloid cells journal, 2283-94 in host defence and adaptive immune responses against de 6. L. R. Huang, Wohlleber, D., Reisinger, F., Jenne, C. N., novo infections. Cheng, R. L., Abdullah, Z., Schildberg, F. A., Odenthal, M., Dienes, H. P., van Rooijen, N., Schmitt, E., Garbi, N., Croft, M., Education / Training Kurts, C., Kubes, P., Protzer, U., Heikenwalder, M. and Knolle, University of Cologne, Immunology, PhD, 2007 P. A. (2013): Intrahepatic myeloid-cell aggregates enable local University of Bonn, Biology, Diploma Thesis, 2004 proliferation of CD8(+) T cells and successful immunotherapy against chronic viral liver infection. Nature immunology, 574-83 7. Abdullah Z., Schlee, M., Roth, S., Mraheil, M. A., Barchet, Appointments / Positions Held W., Bottcher, J., Hain, T., Geiger, S., Hayakawa, Y., Fritz, J. H., Since 2015 Civril, F., Hopfner, K. P., Kurts, C., Ruland, J., Hartmann, G., Group Leader at the Institute of Experimental Immunology, Chakraborty, T. and Knolle, P. A. (2012): RIG-I detects infection University of Bonn, Germany with live Listeria by sensing secreted bacterial nucleic acids. 2012 - 2015 The EMBO journal, 4153-64 Senior Group Leader at the Institutes of Molecular Medicine 8. Abdullah Z., Geiger, S., Nino-Castro, A., Bottcher, J. and Experimental Immunology, University of Bonn, Germa- P., Muraliv, E., Gaidt, M., Schildberg, F. A., Riethausen, K., ny Flossdorf, J., Krebs, W., Chakraborty, T., Kurts, C., Schultze, 2009 - 2012 J. L., Knolle, P. A. and Klotz, L. (2012): Lack of PPARgamma Junior Research Group Leader of Bonfor at the Institutes of in myeloid cells confers resistance to Listeria monocytogenes infection. PloS one, e37349 Molecular Medicine and Experimental Immunology, Univer- 9. Abdullah Z., Saric, T., Kashkar, H., Baschuk, N., Yazdan- sity of Bonn, Germany panah, B., Fleischmann, B. K., Hescheler, J., Kronke, M. and 2008 - 2009 Utermohlen, O. (2007): Serpin-6 expression protects embry- Postdoctoral Research Fellow, Institute of Medical Micro- onic stem cells from lysis by antigen-specific CTL. Journal of biology, Immunology and Hygiene, University of Cologne, immunology, 3390-9 Germany 10. A. Popov*, Abdullah, Z*., Wickenhauser, C., Saric, T., Driesen, J., Hanisch, F. G., Domann, E., Raven, E. L., Dehus, Honors / Awards O., Hermann, C., Eggle, D., Debey, S., Chakraborty, T., Kro- 2014 nke, M., Utermohlen, O. and Schultze, J. L. (2006): Indoleam- DFG TRR57 “Organ Fibrosis: From Mechanisms of Injury to ine 2,3-dioxygenase-expressing dendritic cells form suppura- Modulation of Disease” (Female Scientist Support Program) tive granulomas following Listeria monocytogenes infection. 2012 The Journal of clinical investigation, 3160-70 DFG TRR57 “Organ Fibrosis: From Mechanisms of Injury to *These authors contributed equally Modulation of Disease” (Female Scientist Support Program)

165 10 Most Relevant Publications for PD Dr. Marc Beyer 2001 - 2002 PD Dr. Marc Beyer, MD 1. Beyer M, Abdullah Z, Chemnitz JM, Maisel D, Sander Prof. Matthias Geyer, PhD Visiting Scientist, Computational and Structural Biology J, Lehmann C, Thabet Y, Shinde PV, Schmidleithner L, Programme, European Molecular Biology Laboratory, Life and Medical Sciences Institute (LIMES) Köhne M, Trebicka J, Schierwagen R, Hofmann A, Popov Institute of Innate Immunity Heidelberg, Germany A, Lang KS, Oxenius A, Buch T, Kurts C, Heikenwalder M, 1998 - 2001 Fätkenheuer G, Lang PA, Hartmann P, Knolle PA, Schultze Research associate at the Howard Hughes Medical new Member since 2015 JL. 1. Tumor-necrosis factor impairs CD4(+) T cell-medi- new Member since 2014 Institute, Dept. of Medicine, Microbiology and Immunology, ated immunological control in chronic viral infection. Nat University of California at San Francisco, San Francisco, Immunol. 2016 Mar 7 USA 2. Schmidt SV, Krebs W, Ulas T, Xue J, Baßler K, Günther 1995 - 1998 P, Hardt AL, Schultze H, Sander J, Klee K, Theis H, Kraut Research fellow in the Dept. of Biophysics, Max-Planck- M, Beyer M, Schultze JL. The transcriptional regulator Institute for Medical Research, Heidelberg, Germany network of human inflammatory macrophages is defined by open chromatin. Cell Res. 2016 Feb. Honors / Awards 3. Schultze JL, Beyer M. Myelopoiesis Reloaded: Sin- 2008 gle-Cell Transcriptomics Leads the Way. Immunity. 2016 Editorial Board Member: Cytoskeleton Jan 19. 2001 4. Böttcher JP, Beyer M, Meissner F, Abdullah Z, Sander Habilitation fellowship of the Peter and Traudl Engelhorn- J, Höchst B, Eickhoff S, Rieckmann JC, Russo C, Bauer T, Stiftung, Penzberg Flecken T, Giesen D, Engel D, Jung S, Busch DH, Protzer 1998 Rheinische Friedrich-Wilhelms-Universität Bonn U, Thimme R, Mann M, Kurts C, Schultze JL, Kastenmüller Rheinische Friedrich-Wilhelms-Universität Bonn Long-term fellowship of the European Molecular Biology Life and Medical Sciences Institute (LIMES) W, Knolle PA. Functional classification of memory CD8(+) T Institute of Innate Immunity Organization (EMBO), Heidelberg Genomics & Immunoregulation, Group leader cells by CX3CR1 expression. Nat Commun. 2015 Sep 25. Department of Structural Immunology 1995 E-Mail: [email protected] 5. Krebs W, Schmidt SV, Goren A, De Nardo D, Labzin L, E-Mail: [email protected] Postdoctoral fellowship of the German Science Foundation Bovier A, Ulas T, Theis H, Kraut M, Latz E, Beyer M, Schul- (DFG) Research Expertise tze JL. Optimization of transcription factor binding map Research Expertise accuracy utilizing knockout-mouse models. Nucleic Acids 10 Most Relevant Publications for Prof. Matthias Geyer Marc Beyer’s scientific focus is on the characterization of The Geyer lab is interested in the regulation of transcription Res. 2014 2014 Dec 1;42(21):13051-60. 1. Greifenberg AK, Hönig D, Pilarova K, Düster R, Bartholo- immunoregulatory mechanisms in myeloid and T cells. 6. Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W, and the molecular mechanisms that govern immune receptor Based on transcriptomic and epigenetic discovery his activation. We use a variety of techniques from molecular meeusen K, Bösken CA, Anand K, Blazek D, Geyer M (2016). Quester I, De Nardo D, Gohel TD, Emde M, Schmidleithner Structural and functional analysis of the Cdk13/Cyclin K com- group uses genetic engineering to study fundamental mo- biology and biochemistry to structural biology to analyze L, Ganesan H, Nino-Castro A, Mallmann MR, Labzin L, plex. Cell Rep. 14, 320–331. lecular mechanisms of immunoregulation. interaction between proteins, RNA, lipids, and ligands. The Theis H, Kraut M, Beyer M, Latz E, Freeman TC, Ulas T, 2. Kühn S, Erdmann C, Kage, F, Block, J, Schwenkmezger Schultze JL. Transcriptome-based network analysis reveals transcription cycle is regulated by cyclin-dependent kinases L, Steffen A, Rottner K, Geyer M (2015). Structure of the Education / Training a spectrum model of human macrophage activation. Immu- that phosphorylate the RNA polymerase II. We analyze the FMNL2–Cdc42 complex yields insights in lamellipodia and University of Bonn, Germany, Life & Medical Sciences, nity. 2014 Feb 20;40(2):274-88. transition from transcription initiation to productive elongation filopodia formation. Nat. Commun. 6: 7088. Habilitation, 2015 7. Sommer D, Peters A, Wirtz T, Mai M, Ackermann J, in eukaryotic cells. We study the molecular and structural 3. Bösken CA, Farnung L, Hintermair C, Merzel Schachter University of Cologne, Germany, Medicine, MD thesis, 2005 Thabet Y, Schmidt J, Weighardt H, Wunderlich FT, Degen mechanisms that determine the activity and regulation of M, Vogel-Bachmayr K, Blazek D, Anand K, Fisher RP, Eick University of Heidelberg, Germany, Bioinformatics, J, Schultze JL, Beyer M. Efficient genome engineering by transcription-controlling kinases, as well as their inhibition D, Geyer M (2014). The structure and substrate specificity of Postgraduate program, 2004 targeted homologous recombination in mouse embryos by small molecular compounds. We recently also focused human Cdk12/Cyclin K. Nat. Commun. 5: 3505. University of Cologne, Germany, Medicine, Medicine Fellow using transcription activator-like effector nucleases. Nat on the analysis of receptor activation of NLRP3 and forma- 4. Eick D, Geyer M (2013). The RNA polymerase II car- 2002 - 2004 Commun. 2014 Jan 13;5:3045. tion of the NLRP3/ASC/caspase inflammasome. Besides boxy-terminal domain (CTD) code. Chem. Rev. 113, 8456– 8490. University of Cologne, Germany, Medicine, MD, 2002 8. Beyer M, Mallmann MR, Xue J, Staratschek-Jox A, NACHT-domain containing proteins, Toll-like receptors, RIG-I 5. Czudnochowski N, Bösken CA, Geyer M (2012). Serine-7 Vorholt D, Krebs W, Sommer D, Sander J, Mertens C, and the cGAS-STING pathway mediate the immune-recognition of pathogens. We aim at identifying target sites in these but not serine-5 phosphorylation primes RNA polymerase II Appointments / Positions Held Nino-Castro A, Schmidt SV, Schultze JL. High-resolu- CTD for P-TEFb recognition. Nat. Commun. 3: 842. tion transcriptome of human macrophages. PLoS One. immune regulators that allow for the specific interference with Since 2014 the immune system, e.g., by small molecular compounds. 6. Vollmuth F, Geyer M (2010). Interaction of propionylated Group leader, University of Bonn, Germany 2012;7(9):e45466. and butyrylated histone H3 lysine marks with Brd4 bromo- 2008 - 2013 9. Beyer M, Schumak B, Weihrauch MR, Andres B, Giese domains. Angew. Chem. Int. Ed. Engl. 49, 6768–6772. Education / Training Senior postdoctoral research fellow, University of Bonn, T, Endl E, Knolle PA, Classen S, Limmer A, Schultze JL. In 7. Gerlach H, Laumann V, Martens S, Becker CF, Goody RS, Germany vivo expansion of naïve CD4+ CD25(high) FOXP3+ regula- University of Heidelberg, Germany, Biochemistry, Geyer M (2010). HIV-1 Nef membrane association depends 2004 - 2007 tory T c ells in patients with colorectal carcinoma after IL-2 Habilitation, 2006 on charge, curvature, composition and sequence. Nat. Chem. Postdoctoral research fellow, University of Cologne, Ger- administration. PLoS One. 2012;7(1):e30422. University of Heidelberg, Germany, Biophysics, PhD, 1995 Biol. 6, 46–53. many 10. Beyer M, Thabet Y, Müller RU, Sadlon T, Classen S, University of Heidelberg, Germany, Physics, Diploma, 1991 8. Anand K, Schulte A, Vogel-Bachmayr K, Scheffzek K, 2002 - 2004 Lahl K, Basu S, Zhou X, Bailey-Bucktrout SL, Krebs W, Geyer M (2008). Structural insights into the cyclin T1-Tat-TAR RNA transcription activation complex from EIAV. Nat. Struct. Medicine fellow, University of Cologne, Germany Schönfeld EA, Böttcher J, Golovina T, Mayer CT, Hofmann Appointments / Positions Held Mol. Biol. 15, 1287–1292. A, Sommer D, Debey-Pascher S, Endl E, Limmer A, Hip- 2014 - present pen KL, Blazar BR, Balderas R, Quast T, Waha A, Mayer 9. Nekrep N, Jabrane-Ferrat N, Wolf HM, Eibl MM, Geyer M, Group leader Structural Immunology, University of Bonn, Peterlin BM (2002). Mutation in a winged-helix DNA-binding G, Famulok M, Knolle PA, Wickenhauser C, Kolanus W, Germany Schermer B, Bluestone JA, Barry SC, Sparwasser T, Riley motif causes atypical bare lymphocyte syndrome. Nat. Immu- 2012 - 2014 nol. 3, 1075–1081. JL, Schultze JL. Repression of the genome organizer Group leader Physical Biochemistry, Research center 10. Antz C, Geyer M, Fakler B, Schott MK, Guy HR, Frank R, SATB1 in regulatory T cells is required for suppressive func- caesar, Bonn, Germany Ruppersberg JP, Kalbitzer HR. (1998). NMR structure of inac- tion and inhibition of effector differentiation. Nat Immunol. 2003 - 2012 tivation gates from mammalian voltage-dependent potassium 2011 Aug 14;12(9):898-907. Group leader, Department of Physical Biochemistry, Max channels. Nature 385, 272–275. Planck Institute of Molecular Physiology, Dortmund, Germany

166 167 2014 Most Relevant Publications for Prof. Michael Hölzel Poster Prize for best abstract in the category “Immu- 1. Riesenberg R, Groetchen A, Siddaway R, Bald T, Rein- Dr. Annkristin Heine, MD notherapy“ of the German Society for Hematology and Prof. Michael Hölzel, MD Institute of Experimental Immunology hardt J, Smorra D, Kohlmeyer J, Renn M, Phung B, Aymans Oncology Institute of Clinical Chemistry and Clinical Pharmacology P, Schmidt T, Hornung V, Davidson I, Goding CR, Jönsson Medical Clinic III for Oncology, Hematology and Rheumatology 2012 G, Landsberg J, Tüting T, Hölzel M (2015) MITF and c-Jun BONFOR young scientists award in the category “post- antagonism interconnects melanoma dedifferentiation with new Member since 2015 doc“ new Member since 2013 pro-inflammatory cytokine responsiveness and myeloid cell 2006 recruitment. Nature Communications. 6:8755´ Carl-Liebermeister prize for excellent scientific research of 2. Hölzel M, Landsberg J, Glodde N, Bald T, Rogava M, medical students Riesenberg S, Becker A, Jönsson G, Tüting T. (2015epub) A Preclinical Model of Malignant Peripheral Nerve Sheath Tu- mor-like Melanoma Is Characterized by Infiltrating Mast Cells. Cancer Res. 76(2):251-63. 10 Most Relevant Publications for Dr. Annkristin Heine 3. Bald, T., Landsberg, J., Lopez-Ramos, D., Renn, M., 1. Heine A, Schilling J, Grünwald B, Krüger A, Gevensleben Glodde, N., Jansen, P., Gaffal, E., Steitz, J., Tolba, R., Kalinke, H, Held SAE, Garbi N, Kurts C, Brossart P, Knolle P, Diehl L U., Limmer, A., Jönsson, G., Hölzel, M., Tüting T (2014). and Höchst B. The induction of human myeloid-derived sup- Immune-cell poor melanomas benefit from PD-1 blockade pressor cells through hepatic stellate cells is dose-dependently after targeted type I IFN activation. Cancer Discovery, 2014 inhibited by the tyrosine kinase inhibitors nilotinib, dasatinib Mar 3. Epub ahead of print. and sorafenib, but not sunitinib. Cancer Immunol Immunother- 4. Bald, T., Quast, T., Landsberg, J., Rogava, M., Glodde, apy 2016 Mar;65(3):273-82 N., Lopez-Ramos, D., Kohlmeyer, J., Riesenberg, S., van 2. Rittig SM, Haentschel M, Weimer KJ, Heine A, Muller Rheinische Friedrich-Wilhelms-Universität Bonn Rheinische Friedrich-Wilhelms-Universität Bonn den Boorn-Konijnenberg, D., Hömig-Hölzel, C., Reuten, MR, Brugger W, Horger MS, Maksimovic O, Stenzl A, Hoerr I, Institute of Experimental Immunology and Medical Clin- Unit for RNA Biology, Institute of Clinical Chemistry and R. Schadow, B., Weighardt, I., Wenzel, D., Helfrich, I., Rammensee HG, Holderried TA, Kanz L, Pascolo S, Brossart ic III for Oncology, Hematology and Rheumatology Clinical Pharmacology Schadendorf, D., Bloch, W.,. Bianchi, M.E., Koch, M., P. Long-term survival correlates with immunological respons- Fleischmann, B.K., Förster, I., Kastenmüller, W., Kolanus, W., E-Mail: [email protected] es in renal cell carcinoma patients treated with mRNA-based E-Mail: [email protected] Hölzel, M.*, Gaffal, G.*, Tüting, T* (*corresponding authors). immunotherapy. Oncoimmunology 2015 Oct 29;5(5) (2014). Ultraviolet radiation-induced inflammation promotes an- Research Expertise 3. Held SAE*, Heine A*, Kesper AR, Beckers A, Wolf D, Bros- Research Expertise giotropism and metastasis in melanoma. Nature, 507, 109-13. sart P. Interferon gamma modulates sensitivity of CML cells to Dr. Heine and her group are interested in the mechanisms Michael Hölzel has long-standing research expertise in 5. Landsberg, J., Kohlmeyer, J., Renn, M., Bald, T., Rogava, tyrosine kinase inhibitors. Oncoimmunology, in press governing antigen cross-presentation and cytotoxic T cell the field of tumor biology and functional genomics with a M., Cron, M., Fatho, M., Lennerz, V., Wölfel, T., Hölzel, M., 4. Heine A, Held SAE, Daecke SN, Riethausen K, Flores C, Tüting, T. (2012) Melanomas resist T-cell therapy through induction in the context of anti-tumor immune responses. Kurts C and Brossart P. The VEGF-receptor inhibitor axitinib particular focus on neural crest derived tumors such as Effective cancer vaccines should not only induce strong melanoma. Currently his group investigates how the im- inflammation-induced reversible dedifferentiation. Nature, 490, impairs dendritic cell phenotype and function. PlosOne, 2015 412–416. and durable T cell responses, but also optimally modulate mune system crosstalks with the tumor cells in response to Jun 4;10(6):e0128897 6. Huang, S., Hölzel, M., Knijnenburger, T., Schlicker, A., the balance between suppressive and stimulatory factors danger and proinflammatory signals released by therapy- 5. Schonberg K, Rudolph J, Vonnahme M, Parampalli Roepman, P., McDermott, U., Garnett, M.J., Grernrum, W., in the tumor microenvironment. The aim of her research is Yajnanarayana S, Cornez I, Hejazi M, Manser A, Uhrberg M, induced tumor tissue injury. A central hypothesis is that Sun, C., Prahallad, A., Groenendijk, F.H., Mittempergher, L., the identification of novel immunotherapeutic strategies that Verbeek W, Koschmieder S, Brummendorf TH, Brossart P, this reciprocal communication drives therapy relapse due Nijkamp, W., Neefjes, J., Salazar, R., Ten Dijke, P., Uramoto, accomplish both, with a special focus on different pathways Heine A, Wolf D. JAK inhibition impairs NK cell function in to rewiring of survival and differentiation pathways in tumor H., Tanaka, F., Beijersbergen, R.L., Wessels, L.F., Bernards, of dendritic cell licensing and chemokine receptor modula- myeloproliferative neoplasms. Cancer Res. 2015 Apr 1. pii: cells. This knowledge is critically needed for the rational R. (2012) MED12 controls the response to multiple cancer tion. canres.3198.2014 combination of immunotherapies and targeted signal drugs through regulation of TGFβ receptor signaling. Cell, 151, 6. Parampalli Yajnanarayana S, Stübig T, Cornez I, Alchalby transduction inhibitors in the clinic. 937–950. Education / Training H, Schönberg K, Rudolph J, Triviai I, Wolschke C, Heine A, 7. Hölzel, M.*, Huang, S.*, Koster, J., Ora, I., Lakeman, A., University of Bonn, Germany, Internal Medicine, Hematolo- Brossart P, Kröger N, Wolf D. JAK1/2 inhibition impairs T cell Education / Training Caron, H., Nijkamp, W., Xie, J., Callens, T., Asgharzadeh, S., function in vitro and in patients with myeloproliferative neo- gy, Oncology, Medical Specialist, 2013 University of Munich, Germany, Medicine, MD thesis, 2004 Seeger, RC., Messiaen, L., Versteeg, R., Bernards, R. NF1 University of Tübingen, Germany, Clinical Immunology, MD plasms. Br J Haematol. 2015 Mar 30 is a tumor suppressor in neuroblastoma that determines 7. , Brossart P, Wolf D. Ruxolitinib is a potent immu- University of Munich, Germany, Medicine MD, 2003 thesis, 2006 Heine A retinoic acid response and disease outcome. Cell, 2010; 142, nosuppressive compound: is it time for anti-infective prophy- University of Tübingen, Germany; University of Bordeaux, 218–229. laxis? Blood. 2013 Nov 28;122(23):3843-4 Appointments / Positions Held France; Mount Sinai School of Medicine, New York, USA, 8. Hölzel M, Orban M, Hochstatter J, Rohrmoser M, Harasim 8. Heine A, Held SAE, Daecke SN, Wallner S, Yajnanaraya- 2012 - present MD, 2006 T, Malamoussi A, Kremmer E, Längst G, Eick D. (2010) Defects na SM, Kurts C, Wolf D and Brossart P. The JAK-inhibitor W2 Professor, Unit for RNA Biology, Institute of Clinical in 18 S or 28 S rRNA processing activate the p53 pathway. J Ruxolitinib impairs dendritic cell function in vitro and in vivo. Chemistry and Clinical Pharmacology, University of Bonn, Biol Chem., 285, 6364-70. Appointments / Positions Held Blood. 2013 Aug 15;122(7):1192-202 Germany 9. Huang S, Laoukili J, Epping MT, Koster J, Hölzel M., since 2013 9. Held SAE, Duchardt KM, Tenzer S, Rückrich T, von 2007 - 2011 Westerman BA, Nijkamp W, Hata A, Asgharzadeh S, Seeger Schwarzenberg K, Bringmann A, Schild HJ, Driessen C, Senior Physician in the Medical Clinic III for Oncology, He- Postdoctoral Fellow, Laboratory of Rene Bernards, The RC, Versteeg R, Beijersbergen RL, Bernards R. (2009) ZNF423 Brossart P and Heine A. Imatinib mesylate and nilotinib affect matology and Rheumatology, University of Bonn, Germany Netherlands Cancer Institute, Amsterdam, The Netherlands is critically required for retinoic acid-induced differentiation since 2015 MHC-class I presentation by modulating the proteasomal pro- and is a marker of neuroblastoma outcome. Cancer Cell, 15, cessing of antigenic peptides. Cancer Immunol Immunother. 2003 - 2006 Group leader of a clinical-translational junior research Residency Hematology/Oncology, University Hospital 328-40. group, Institute of Experimental Immunology and Medical 2012 Nov 25. 10. Heine A, Grünebach F, Holderried T, Appel S, Weck MM, Munich (LMU), Germany Clinic III, University of Bonn, Germany *These authors contributed equally Dörfel D, Sinzger C, Brossart P. Transfection of dendritic cells 2013 - 2014 with in vitro-transcribed CMV RNA induces polyclonal CD8+- Honors / Awards Group leader of a BONFOR junior research group, Institute and CD4+-mediated CMV-specific T cell responses. Mol Ther. 2002 of Experimental Immunology, University of Bonn, Germany 2006 Feb;13(2):280-8. Scholarship „Harvard-Munich Alliance“ 2010 - 2012 Postdoctoral fellow, Institute of Experimental 1999 Immunology, University of Bonn, Germany *These authors contributed equally Scholarship “Studienstiftung des deutschen Volkes”

Honors / Awards 2015 Lisec-Artz-price for best junior scientist in the field of oncology

168 169 10 Most Relevant Publications for Prof. Wolfgang 10 Most Relevant Publications for Dr. Martin Schlee Prof. Wolfgang Kastenmüller, MD Kastenmüller Dr. Martin Schlee, PhD 1. Herzner AM, Hagmann CA, Goldeck M, Wolter S, Kübler 1. Eickhoff S, Brewitz A, Gerner MY, Klauschen F, Koman- K, Wittmann S, Gramberg T, Andreeva L, Hopfner KP, Mertens C, Zillinger T, Jin T, Xiao TS, Bartok E, Coch C, Ackermann D, Institute of Molecular Medicine der K, Hemmi H, Garbi N, Kaisho T, Germain RN, Kast- Institute of Clinical Chemistry and Clinical Pharmacology Hornung V, Ludwig J, Barchet W, Hartmann G and Schlee M. enmuller W. 2015. Robust Anti-viral Immunity Requires Sequence-specific activation of cGAS by Y-form DNA struc- Multiple Distinct T Cell-Dendritic Cell Interactions. Cell 2015 tures as found in primary HIV-1 cDNA. Nat Immunol. 2015. new Member since 2013 Sep 10;162(6):1322-37 new Member since 2015 16(10):1025-33 2. Franklin BS, Bossaller L, De Nardo D, Ratter JM, 2. Schuberth-Wagner C, Ludwig J, Bruder AK, Herzner AM, Stutz A, Engels G, Brenker C, Nordhoff M, Mirandola SR, Zillinger T, Goldeck, M, Schmidt T, Schmid-Burgk L, Kerber R, Al-Amoudi A, Mangan MS, Zimmer S, Monks BG, Fricke Wolter S, Stümpel JP, Roth A, Bartok E, Drosten C, Coch C, M, Schmidt RE, Espevik T, Jones B, Jarnicki AG, Hansbro Hornung V, Barchet W, Kümmerer BM, Hartmann G, Schlee PM, Busto P, Marshak-Rothstein A, Hornemann S, Aguzzi M. A conserved histidine in the RNA sensor RIG-I controls A, Kastenmuller W, Latz E. The adaptor ASC has extracel- immune tolerance to N1-2’O-methylated self RNA. Immunity. lular and ‘prionoid’ activities that propagate inflammation. 2015. 43(1):41-51 Nat Immunol: 2014 Aug;15(8):727-37. 3. Goubau D, Schlee M*, Deddouche S, Pruijssers AJ, 3. Honda T, Egen JG, Lammermann T, Kastenmuller Zillinger T, Goldeck M, Schuberth C, Van der Veen AG, Fujimu- W, Torabi-Parizi P, Germain RN. 2014. Tuning of antigen ra T, Rehwinkel J, Iskarpatyoti JA, Barchet W, Ludwig J, Der- sensitivity by T cell receptor-dependent negative feedback mody TS, Hartmann G, Reis e Sousa C. Antiviral immunity via controls T cell effector function in inflamed tissues. Immuni- RIG-I-mediated recognition of RNA bearing 5’-diphosphates. ty 40: 235-47 Nature. 2014. 514(7522):372-5 (JIF 41.3) 4. Coch C, Lück C, Schwickart A, Putschli B, Renn M, Höller Rheinische Friedrich-Wilhelms-Universität Bonn 4. Bald T, Quast T, Landsberg J, Rogava M, Glodde N, Rheinische Friedrich-Wilhelms-University Bonn, Univer- T, Barchet W, Hartmann G, Schlee M. A Human In Vitro Whole Lopez-Ramos D, Kohlmeyer J, Riesenberg S, van den Institute of Molecular Medicine sity Hospital, Institute of Clinical Chemistry and Clinical Blood Assay to Predict the Systemic Cytokine Response to E-Mail: [email protected] Boorn-Konijnenberg D, Hömig-Hölzel C, Reuten R, Schad- Pharmacology Therapeutic Oligonucleotides Including siRNA. PLoS One. ow B, Weighardt H, Wenzel D, Helfrich I, Schadendorf D, E-Mail: [email protected] 2013. 8: e71057. doi:10.1371/journal.pone.0071057 Research Expertise Bloch W, Bianchi ME, Lugassy C, Barnhill RL, Koch M, 5. Hagmann CA, Herzner AM, Abdullah Z, Zillinger T, Jakobs Fleischmann BK, Förster I, Kastenmuller W, Kolanus W, The scientific focus of his group are cellular interactions and C, Schuberth C, Coch C, Higgins PG, Wisplinghoff H, Barchet Hölzel M, Gaffal E, Tüting T. Ultraviolet-radiation-induced Research Expertise W, Hornung V, Hartmann G, Schlee M. RIG-I detects triphos- cell-cell communication in the context of acute infections. inflammation promotes angiotropism and metastasis in The focus of Martin Schlee’s research group is immune phorylated RNA of Listeria monocytogenes during infection in Central techniques are live intravital imaging and histocy- melanoma. Nature. 2014 Mar 6;507(7490):109-13. recognition and immune tolerance of viral and endogenous non-immune cells. PLoS One. 2013. 8(4): e62872 tometry. 5. Lämmermann T, Afonso PV, Angermann BR, Wang JM, nucleic acids. Nucleic acid receptors of the innate immune 6. Abdullah Z, Schlee M*, Roth S, Mraheil MA, Barchet W, Kastenmuller W, Parent CA, Germain RN.: Neutrophil system initiate and control the antiviral immune response of Böttcher J, Hain T, Geiger S, Hayakawa Y, Fritz JH, Civril F, Education / Training swarms require LTB4 and integrins at sites of cell death in the infected organism. The detection of pathogenic RNA/ Hopfner K-P, Kurts C, Ruland J, Hartmann G, Chakraborty Laboratory of Systems Biology NIH/USA, vivo. Nature. 2013 Jun 20;498(7454):371-5. DNA by nucleic acid receptors is based on recognition of T and Knolle PA. RIG-I detects infection with live Listeria by Ronald N. Germain, 2008 - 2012 6. Kastenmuller W., Brandes, M., Wang, Z., Herz, J., unusual RNA/DNA localization, structure and modifications, sensing secreted bacterial nucleic acids. EMBO J. 2012. 31, Technical University of Munich, Germany, Specialization Egen YG., Germain, RN.: Peripheral pre-positioning and so-called pattern recognition motifs. The challenge here is 4153 – 4164. 7. Coch C, Busch N, Wimmenauer V, Hartmann E, Janke Infectious Disease, 2008 local CXCL9-mediated guidance orchestrate rapid memory that the innate immune system detects sensitively patho- M, Abdel-Mottaleb MMA, Lamprecht A, Ludwig J, Barchet Technical University of Munich, Germany, Medicine, MD CD8+ T cell responses in the lymph node. Immunity, 2013, genic nucleic acids without false activation by the endoge- W, Schlee M* , Hartmann G*. Higher activation of TLR9 in thesis, 2003 Jan 24: nous nucleic acids. While an insensitive recognition favors plasmacytoid dendritic cells by microbial DNA compared with Technical University of Munich, Germany, Medicine, 7. Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, the spread of infection, an excessive immune detection of self-DNA based on CpG-specific recognition of phosphodi- 1997 - 2002 Kastenmuller W, Deming C, Quinones M, Koo L, Conlan nucleic acids leads to autoimmune diseases. The group has ester DNA. Journal of Leukocyte Biology. 2009. 86: 663-670, Universities of Regensburg, Germany, Medicine, S, Spencer S, Hall JA, Dzutsev A, Kong H, Campbell DJ, identified and characterized recognition motifs of the cyto- 8. Schlee M, Roth A, Hornung V, Hagmann CA, Wimmenau- 1995 - 1997 Trinchieri G, Segre JA, Belkaid Y. 2012. Compartmentalized solic DNA receptor cGAS and the cytosolic RNA receptor er V, Barchet W, Coch C, Janke M, Mihailovic A, Wardle G, control of skin immunity by resident commensals. Science RIG-I and endogenous as well as viral RNA modifications Juranek S, Kato H, Kawai T, Poeck H, Fitzgerald KA, Takeuchi Appointments / Positions Held 337: 1115-9 that prevent recognition by RIG-I. O, Akira S, Tuschl T, Latz E, Ludwig J, Hartmann G. Recogni- 2013 8. Kastenmuller W., Torabi-Parizi, P., Subramanian, S., tion of 5’ Triphosphate by RIG-I Helicase Requires Short Blunt Associate Professor, University of Bonn, Germany Lammermann, T., Germain, R.N.: A spatially-organized Education / Training Double-Stranded RNA as Contained in Panhandle of Nega- multicellular innate immune response in the lymph node tive-Strand Virus. Immunity. 2009. 31(1): 25-34 2008 - 2012 University of Munich, Germany, Biochemistry, PhD, 2003 limits the systemic spread of tissue-invasive pathogens. 9. Schlee M, Hölzel M, Bernard S, Mailhammer R, Schuh- Postdoctoral Fellow, NIH/Besthesda USA University of Bielefeld, Germany, Biochemistry, Diploma, Cell, 2012, Sep 14; 150(6):1235-48. macher M, Reschke J, Eick D, Marinkovic D, Wirth T, Ros- 2002 - 2008 1999 Clinical Fellow/Post-Doc, Technical University of Munich, 9. Gerner, M.Y., Kastenmuller W., Ifrim, I., Kabat J., enwald A, Staudt LM, Eilers M, Baran-Marszak F, Fagard R, Germain, R.N.: Histo-Cytometry: in situ multiplex cell Feuillard J, Laux G, Bornkamm GW. C-myc activation impairs Germany Appointments / Positions Held phenotyping, quantification, and spatial analysis applied the NF-kappaB and the interferon response: implications for 2006 - present the pathogenesis of Burkitt’s lymphoma. Int J Cancer. 2007 Honors / Awards to dendritic cell subset analysis in lymph nodes. Immunity, 2012 Aug 24;37(2):364-76. Group Leader, Institute of Clinical Chemistry and Clinical 120(7):1387-95 2012 10. Schlee M, Krug T, Gires O, Zeidler R, Hammerschmidt 10. Kastenmuller W, Gasteiger G, Gronau JH, Baier R, Pharmacology, University of Bonn, Germany CIG - Best Paper Award NIH W, Mailhammer R, Laux G, Sauer G, Lovric J, Bornkamm Ljapoci R, Busch DH, Drexler I. 2007. Cross-competition 2005 - 2006 2003 GW. Identification of Epstein-Barr virus (EBV) nuclear antigen of CD8+ T cells shapes the immunodominance hierarchy PostDoc, Division of Clinical Pharmacology, University of Dietmar-Zumpf-Promotions Preis 2 (EBNA2) target proteins by proteome analysis: activation during boost vaccination. J Exp Med 204: 2187-98 Munich, Germany 2003 - 2005 of EBNA2 in conditionally immortalized B cells reflects early events after infection of primary B cells by EBV. J Virol. 2004 PostDoc, Institute of Clinical Molecular Biology and Tumor 78(8):3941-52 Genetics, Helmholtz Center Munich, Germany

Honors / Awards 2009 Bonfor Junior research Group award

170 171 10 Most Relevant Publications for Dr. Andreas Schlitzer Honors / Awards Dr. Andreas Schlitzer, PhD 1. Paul, F., Arkin, Y., Giladi, A., Jaitin, D. A., Kenigs- Prof. Sven Wehner, PhD 2013 berg, E., Keren-Shaul, H., …, Schlitzer, A., et al. (2015). ‘Poster of Distinction; Digestive Diesease Week, May 19-22 Life and Medical Sciences Institute (LIMES) Transcriptional Heterogeneity and Lineage Commitment in Department of Surgery San Diego Myeloid Progenitors. Cell, 1–16. 2007 2. Schlitzer, A., Sivakamasundari, V., Chen, J., Bin Su- Best of Abstracts, Detusche Gesellschaft für Chirurgie new Member since 2015 matoh, H. R., Schreuder, J., Lum, J., et al. (2015). Iden- new Member since 2015 tification of cDC1- and cDC2-committed DC progenitors 2005 reveals early lineage priming at the common DC progenitor Best of Abstracts, Deutsche Gesellschaft für Chirurgie’ stage in the bone marrow. Nat Immunol, 1–13. http://doi. org/10.1038/ni.3200 10 Most Relevant Publications for Prof. Sven Wehner 3. Schlitzer, A., McGovern, N., & Ginhoux, F. (2015). 1. Ochoa-Cortes F, Turco F, Linan-Rico A, Soghomonyan Dendritic cells and monocyte-derived cells: Two comple- S, Whitaker E, Wehner S, Cuomo R, Christofi FL. Enteric mentary and integrated functional systems. Seminars in Glial Cells: A New Frontier in Neurogastroenterology and Cell & Developmental Biology. http://doi.org/10.1016/j. Clinical Target for Inflammatory Bowel Diseases. 2016 semcdb.2015.03.011 Feb;22(2):433-49 4. Becher, B.*, Schlitzer, A.*, Chen, J., Mair, F., Suma- 2. Stein K, Stoffels M, Lysson M, Schneiker B, Dewald O, toh, H. R., Teng, K. W. W., et al. (2014). High-dimensional Krönke G, Kalff JC, Wehner S. A role for 12/15-lipoxygen- analysis of the murine myeloid cell system. Nat Immunol, ase-derived proresolving mediators in postoperative ileus: 15(12), 1181–1189. doi:10.1038/ni.3006. Co-first author protectin DX-regulated neutrophil extravasation. J Leukoc Biol. 2016 Feb;99(2):231-9. Rheinische Friedrich-Wilhelms-Universität Bonn, Life 5. McGovern*, Schlitzer, A.*, N., Gunawan, M., Jardine, Rheinische Friedrich-Wilhelms-University Bonn, De- 3. Hong GS, Schwandt T, Stein K, Schneiker B, Kummer and Medical Sciences Institute (LIMES) L., Shin, A., Poyner, E., et al. (2014). Human dermal CD14+ partment of Surgery, Immune Pathophysiology cells are a transient population of monocyte-derived MP, Heneka MT, Kitamura K, Kalff JC, Wehner S. Effects of E-Mail: [email protected] macrophages. Immunity, 41(3), 465–477. doi:10.1016/j. E-Mail: [email protected] macrophage-dependent peroxisome proliferator-activated immuni.2014.08.006. Co-first author receptor γ signalling on adhesion formation after abdom- Research Expertise Research Expertise 6. Schlitzer, A., & Ginhoux, F. (2014). Organization of the inal surgery in an experimental model. Br J Surg. 2015 The aim of our research is to identify (neuro)-immunologi- Nov;102(12):1506-16. The aim of our research is to understand the complexity mouse and human DC network. Current Opinion in Immu- cal mechanisms contributing to acute (postoperative) and 4. Stoffels B, Hupa KJ, Snoek A, van Bree A, Stein K, and function of dendritic cells and monocytes during health nology, 26, 90–99. doi:10.1016/j.coi.2013.11.002 chronic functional disturbances of the GI tract. In a series Schwandt T, Vilz T, Lysson M, van´t Veer, Hornung V, Kalff and disease. A major focus lies on the developmental pro- 7. Jakubzick, C., Gautier, E. L., Gibbings, S. L., Sojka, D. of publications our group demonstrated that interactions JC, de Jonge WJ, Wehner S. Interleukin-1 receptor signal- cesses leading to the functional specialization of dendritic K., Schlitzer, A., Johnson, T. E., et al. (2013). Minimal dif- of resident immune cells and the enteric nervous system ing contributes to postoperative ileus by targeting enteric cell subsets and monocytes. To analyse these highly het- ferentiation of classical monocytes as they survey steady- trigger postoperative bowel wall inflammation. This local glial cells. Gastroenterology 2014, 146(1): 176-87. erogeneous compartments we use state of the art technol- state tissues and transport antigen to lymph nodes. Immu- neuroinflammation can be effectively modified by intrinsic 5. Glowka TR, Steinebach A, Schwandt T, Kranz A, Kalff ogies such as single cell mRNA sequencing, multi-colour nity, 39(3), 599–610. doi:10.1016/j.immuni.2013.08.007 and extrinsic neurotransmitters. With international collabo- JC, Wehner S. CGRP release during abdominal surgery fish and advanced flow cytometry. Taken together we are 8. Schlitzer, A., McGovern, N., Teo, P., Zelante, T., rators we also investigate the neuroimmunology of chronic mediates small bowel inflammation and postoperative ileus investigating how the development of dendritic cells and Atarashi, K., Low, D., et al. (2013). IRF4 transcription inflammatory bowel diseases. Currently, we are aiming in a macrophage dependent Neurogastroenterol Motil, monocytes shapes their functional specialization during factor-dependent CD11b+ dendritic cells in human and to understand the initial trigger mechanisms of intestinal 2015, 27(7):1039-49. homeostasis and disease. mouse control mucosal IL-17 cytokine responses. Immuni- ty, 38(5), 970–983. doi:10.1016/j.immuni.2013.04.011 inflammation as well as to identify novel neuro-immune 6. Vilz TO, Sommer MD, Kahl P, Pantelis D, Kalff JC, Weh- 9. Schlitzer, A., Heiseke, A. F., Einwächter, H., Reindl, W., modulatory pathways. This will help us to gather a com- ner S. Oral CPSI-2364 treatment prevents postoperative Education / Training Schiemann, M., Manta, C.- P., et al. (2012). Tissue-spe- prehensive understanding of acute and chronic intestinal ileus in swine without impairment of anastomotic healing. Technical University of Munich, Germany, Immunology, cific differentiation of a circulating CCR9- pDC-like com- inflammatory disorders. Cell.Physiol.Biochem , 2013;32(5):1362-1373. PhD, 2012 mon dendritic cell precursor. Blood, 119(25), 6063–6071. 7. Schwandt T, Schumak B, Jüngerkes F, Gielen G, University of Manchester, UK, Immunology, Master of Sci- doi:10.1182/blood- 2012-03-418400 Education / Training Schmidbauer P, Klocke K, Staratscheck-Jox A, van ence, 2008 10. Schlitzer, A., Loschko, J., Mair, K., Vogelmann, R., University of Bonn, Molecular Medicine, venia legendi, 2012 Rooijen N, Kraal G, Ludwig-Portugall I, Wehner S, Kalff University of Marburg, Germany, Molecular Biology, Bache- Henkel, L., Einwächter, H., et al. (2011). Identification of University of Bonn, Cell Biology, PhD thesis, 2003 JC, Kirschning , Coch C, Kalinke U, Wenzel J, Kurts C, lor of Science, 2007 CCR9- murine plasmacytoid DC precursors with plastici- University of Bonn, Biology, Diploma, 1999 Zawatzky R, Holzmann B, Layland L, Schultze J, Burg- ty to differentiate into conventional DCs. Blood, 117(24), dorf S, Haan J, Knolle J, Franken L, Weber O, Limmer A. Appointments / Positions Held 6562–6570. doi:10.1182/blood- 2010-12-326678 Appointments / Positions Held Expression of type I interferon by splenic macrophages 2015 - present 2016 - present suppresses adaptive immunity during sepsis. EMBO J, Emmy Noether research group leader, Myeloid cell biology, Full Professor for Immune Pathophysiology, University of 2012; 31(1):201-13. University of Bonn, Germany Bonn, Germany 8. Engel DR, Koscielny A Wehner S, Maurer J, Schiwon 2012 - 2015 2013 - 2015 M, Franken L, Schumak B, Limmer A, Sparwasser T, Hirner Postdoctoral Fellow, SIngapore Immunology Network, Asociate Professor, AMC, Amsterdam, Netherlands T, Knolle PA, Kalff JC KurtsC. T helper type 1 memory cells Singapore 2006 - 2013 disseminate postoperative ileus over the entire intestinal Independent workgroup leader and laboratory head, De- tract. Nature Medicine 2010, 16(12), 1407-13. Honors / Awards partment of Surgery, University Bonn, Germany 9. Wehner S, Straesser S, Pantelis D, Sielecki T, de la Cruz VF, Hirner A, Kalff JC. Inhibition of p38 MAP kinase 2015 2003 - 2006 pathway as a target for prophylaxis of postoperative ileus in Bright Sparks award of the German Immunologists associ- Postdoctoral Fellow, Department of Surgery, University of mice. Gastroenterology 2009;136(2):619-629. ation Bonn, Germany 10. Wehner S, Behrendt FF, Lyutenski B, Lysson M, Bauer 2013 - 2016 1999 - 2003 AJ, Kalff JC. Inhibition of Macrophage Function Prevents Junior Invstigator fellowship, Biomedical research council, Research Scientist at Celonic GmBH, Research Center Intestinal Inflammation and Postoperative Ileus in Rodents. Singapore Jülich; Doctoral Student, Institute of Cell Biology, University of Bonn, Germany Gut 2007; 56(2):176-85.

172 173 Society of Mucosal Immunology travel fellowship 2012 Prof. Christoph Wilhelm, PhD NIH Fellow Award for Research Excellence (FARE award) Institute of Clinical Chemistry and Clinical Pharmacology 2012 Human Frontiers Science program postdoctoral fellowship 2010 new Member since 2015 British Society for Immunology travel fellowship for the International Congress of Immunology 2010 European Federation of Immunological Societies travel fellowship for the International Congress of Immunology 2009 European Federation of Immunological Societies travel fellowship for the European Congress of Immunology 2008 MUGEN travel fellowship for ENII-MUGEN Immunology Summer School 2007 Medical Research Council (MRC) Ph.D. studentship

Rheinische Friedrich-Wilhelms-University Bonn, Insti- 10 Most Relevant Publications for Prof. Christoph Wilhelm tute of Clinical Chemistry and Clinical Pharmacology 1. Zhong C, Cui K, Wilhelm C, Hu G, Mao K, Belkaid Y, Zhao K, Zhu J.GATA3 dictates NKp46+ T-bet/RORγt-co-expressing E-Mail: [email protected] ILC3 development and regulates ILC3 homeostasis and function. Nature Immunology 2016. Research Expertise 2. Askenase MH, Han SJ, Byrd AL, Morais da Fonseca D, Prof. Wilhelm has longterm experience in the research of Bouladoux N, Wilhelm C, Konkel JE, Hand TW, Lacerda-Que- a unique group of immune cells termed innate lymphoid iroz N, Su XZ, Trinchieri G, Grainger JR, Belkaid Y. Bone-Mar- cells (ILC). His scientific focus is to understand how these row-Resident NK Cells Prime Monocytes for Regulatory cells protect the barrier sites of our body such as the lung, Function during Infection. Immunity 2015. skin and gut and to understand the maintenance of ILC 3. Naik, S., N. Bouladoux, J.L. Linehan, S.J. Han, O.J. mediated barrier immunity in the context of malnutrition. Harrison, C. Wilhelm, S. Conlan, S. Himmelfarb, A.L. Byrd, C. The overall aim of this research is to understand the link Deming, M. Quinones, J.M. Brenchley, H.H. Kong, R. Tussi- between westernization and the growing health problem of wand, K.M. Murphy, M. Merad, J.A. Segre, and Y. Belkaid. 2015. Commensal-dendritic-cell interaction specifies a unique chronic inflammatory conditions such as inflammatory bowl protective skin immune signature. Nature 2015. disease (IBD) and asthma. 4. Wilhelm C*, Spencer SP*, Yang Q, Hall JA, Bouladoux N, Boyd A, Nutman TB, Urban JF Jr, Wang J, Ramalingam Education / Training TR, Bhandoola A, Wynn TA, Belkaid Y. Adaptation of innate Hofgarten University of Bonn National Institute for Medical Research, London, UK, Immu- lymphoid cells to a micronutrient deficiency promotes type 2 by Frank Luerweg nology, PhD, 2011 barrier immunity. Science 2014 *Primary authors contributed University of Munich, Germany, Biology MSc (Diploma), equally to this work. 2007 5. Turner JE*, Morrison PJ*, Wilhelm C, Wilson M, Ahlfors H, Renauld JC, Panzer U, Helmby H and Stockinger B. (2013) Appointments / Positions Held IL-9-mediated survival of type 2 innate lymphoid cells pro- 2015 - present motes damage control in helminth-induced lung inflammation. Assistant Professor for Immunopathology, University of J Exp Med *Primary authors contributed equally to this work. Bonn, Germany 6. Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, 2015 - present Kastenmuller W, Deming C, Quinones M, Koo L, Conlan S, Principal Investigator, Department of Medicine, University of Spencer S, Hall JA, Dzutsev A, Kong H, Campbell DJ, Trinch- ieri G, Segre JA, Belkaid Y. (2012) Compartmentalized control Bonn, Germany of skin immunity by resident commensals. Science 2011- 2015 7. Wilhelm C, Turner JE, Van Snick J, and Stockinger B. The Postdoctoral Fellow, National Institutes of Health, USA many lives of IL-9: a question of survival? Nature Immunology 2012. Honors / Awards 8. Wilhelm C, Hirota K, Stieglitz B, Van Snick J, Tolaini M, 2015 Lahl K, Sparwasser T, Helmby H and Stockinger B. (2011) An NRW-Return Programme, funding to establish an indepen- IL-9 fate reporter demonstrates the induction of an innate IL-9 dent research programme response in lung inflammation. Nature immunology 2014 9. Li Y, Innocentin S, Withers DR, Roberts NA, Gallagher AR, NIH Fellow Award for Research Excellence (FARE award) Grigorieva EF, Wilhelm C and Veldhoen M. (2011) Exogenous 2014 stimuli maintain intraepithelial lymphocytes via aryl hydrocar- The CIG best paper award, Best publication in cytokine re- bon receptor activation. Cell search for postdoctoral fellow working at the NIH and FDA 10. Veldhoen M, Uyttenhove C, van Snick J, Helmby H, 2014 Westendorf A Buer J, Martin B, Wilhelm C and Stockinger B. (2008) Transforming growth factor-beta ‘reprograms’ the Keystone Symposia travel fellowship for oral presentation at differentiation of T helper 2 cells and promotes an interleukin the Keystone Symposia 2014 9-producing subset. Nature immunology 2013

174 175 2005 Prize of excellence for young researchers for the PhD work, Dr. Ashraf Al-Amoudi, PhD Faculty of Biology and Medicine, University of Lausanne, German Centre for Neurodegenerative Diseases (DZNE) and center of advanced european studies and research (caesar) Lausanne, Switzerland Biosketches 10 Most Relevant Publications for Dr. Ashraf Al- Amoudi 1. Gunkel M, Schöneberg J, Alkhaldi W, Irsen S, Noé F, Kaupp UB, Al-Amoudi A. 2015. Higher-order architecture of rhodopsin in intact photoreceptors and its implication for Core Members phototransduction kinetics. pii: S0969-2126(15)00039-8. doi: 10.1016/j.str.2015.01.015. 2. Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G, Brenker C, Nordhoff M, Mirandola SR, Al-Amoudi A, Mangan MS, Zimmer S, Monks BG, Fricke M, Schmidt RE, Espevik T, Jones B, Jarnicki AG, Hansbro PM, Busto P, Marshak-Rothstein A, Hornemann S, Aguzzi A, Kastenmüller W, Latz E. 2014. The adaptor ASC has extracellular and ‘prionoid’ activities that propagate inflammation. Nat Immunol. 727-37. 3. Al-Amoudi A, Frangakis AS. 2013. Three-dimension- German Centre for Neurodegenerative Diseases (DZNE) al visualization of the molecular architecture of cell-cell and center of advanced european studies and research junctions in situ by cryo-electron tomography of vitreous (caesar) sections. Methods Mol Biol 961: 97-117. E-Mail: [email protected] 4. Al-Amoudi A, Castaño-Diez D, Devos DP, Russell RB, Johnson GT, Frangakis AS. The three-dimensional molec- Research Expertise ular structure of the desmosomal plaque. Proc. Natl. Acad. Sci. 2011,108, 6480-5. Structural biology, cryo-electron tomography, intercellular 5. Al-Amoudi A, Diez DC, Betts MJ, Frangakis AS. 2007. adhesion junctions, synapses, neurodegenerative diseases. The molecular architecture of cadherins in native epidermal desmosomes. Nature 450: 832-7. Education / Training 6. Castano-Diez D, Al-Amoudi A, Glynn AM, Seybert A, University of Lausanne, Switzerland, Life science/EM Frangakis AS. 2007. Fiducial-less alignment of cryo-sec- Structural, Biology, PhD, 2004 tions. J Struct Biol 159: 413-23. University of Lausanne, Switzerland, Physics, Science 7. Al-Amoudi A, Studer D, Dubochet J. 2005. Cutting diploma, 1999 artefacts and cutting process in vitreous sections for Birzeit University, West Bank, Palestine, Physics, B.Sc, cryo-electron microscopy. J Struct Biol 150: 109-21. 1997 8. Al-Amoudi A, Dubochet J, Norlen L. 2005. Nanostruc- ture of the epidermal extracellular space as observed by Appointments / Positions Held cryo-electron microscopy of vitreous sections of human Jan 2010 - present skin. J Invest Dermatol 124: 764-77. Group leader, Cryo-Electron Microscopy and Tomography 9. Norlen L, Al-Amoudi A. 2004. Stratum corneum keratin in neurodegenerative diseases, German Centre for structure, function, and formation: the cubic rod-packing Neurodegenerative Disease (DZNE) and center of advanced and membrane templating model. J Invest Dermatol 123: european studies andresearch (caesar), Bonn 715-32. 2005 - 2009 10. Al-Amoudi A, Chang JJ, Leforestier A, McDowall A, Postdoctoral fellow, Structural and Computational Biology Salamin LM, Norlen LP, Richter K, Blanc NS, Studer D, Unit, European Molecular Biology Laboratory (EMBL), Dubochet J. 2004. Cryo-electron microscopy of vitreous Heidelberg, Germany sections. EMBO J 23: 3583-8. 2004 - 2005 Postdoctoral, Laboratory of Ultrastructure Analysis University of Lausanne, Switzerland

Honors / Awards 2014 - 2017 SFB, Transregio Collaborative Research, TRR83 2012 - 2017 Cluster of Excellence, ImmunoSensation, DFG 2010 - 2014 Wellcome Trust and MRC Career Development Awards - declined 2007 - 2009 Marie Curie Intra-European Fellowship 2006 - 2007 EMBO Fellowship

177 Buddecke-Foundation for the advancement of basic medical University of California, Irvine, CA, USA research 1982 - 1986 Prof. Regina C. Betz, MD 2008 EP-Patent application 07 01 8871.9: “Maintenance of Prof. Anton Bovier, PhD Assistant, Institute for Theoretical Physics, ETH-Zurich Institute of Human Genetics hair growth and treatment of hair loss.” (together with Prof. Institute for Applied Mathematics Nöthen, S. Pasternack Dipl.-biol., and Dr. Al Aboud) Honors / Awards 2008 Lecture Prize at the Annual Meeting of the European Hair Research Society in Genoa, Italy 2014 2006 Gottron-Just-Scientific Prize of the University and City of Member of Selection Committee, Heinz-Maier-Leibnitz prize Ulm, Germany 2013 2002 - 2004 Flemish Research Council Postdoctoral Fellowship Elected Fellow, Institute of Mathematical Statistics 2000 - 2002 DFG Postdoctoral Fellowship 2012 Kloosterman Chair, University Leiden, NL 2010 10 Most Relevant Publications for Prof. Regina Betz Lady Davies Visiting Professor, Technion, Haifa, IL 1. Betz RC, Petukhova L, Ripke S, [..] Clynes D, de Bakker 2010 PIW, Nöthen MM, Daly MJ, Christiano AM: Meta-analysis of genome-wide association studies in alopecia areata resolves HLA Plenary Speaker, Annual Meeting of the German associations and reveals two new susceptibility loci. Nat Commun, Mathematical Association Jan 2015 22, 6:5966 2009 2. Basmanav FB, Oprisoreanu AM, Pasternack SM, Thiele H, Fritz EURANDOM Chair, EURANDOM; Eindhoven, NL G, Wenzel J, Größer L, Wehner M, Wolf S, Fagerberg C, Bygum A, 2008 Altmüller J, Rütten A, Parmentier L, El Shabrawi-Caelen L, Hafner C, Nürnberg P, Kruse R, Schoch S, Hanneken S, Betz RC. 2014. Member of the Selection Committee of the Minerva Rheinische Friedrich-Wilhelms-Universität Bonn Mutations in POGLUT1, encoding protein O-glucosyltransferase Rheinische Friedrich-Wilhelms-Universität Bonn Foundation Institute of Human Genetics 1, cause autosomal dominant Dowling-Degos disease. Am J Hum Institute for Applied Mathematics 2008 Genet 94:135-143. E-Mail: [email protected] E-Mail: [email protected] Member of the Review Board for Mathematics of the 3. Pasternack SM, Refke M, Paknia E, Hennies HC, Franz T, German Research Council Schäfer N, Fryer A, van Steensel M, Sweeney E, Just M, Grimm Research Expertise C, Kruse R, Ferrándiz C, Nöthen MM, Fischer U, Betz RC. 2013. Research Expertise 2006 The aim of our research is the identification and functional Mutations in SNRPE, encoding a core protein of the spliceosome, Invited Speaker at the International Congress of characterization of genes for monogenic and genetically com- cause autosomal-dominant hypotrichosis simplex. Am J Hum The main focus of my work concerns the analysis of Mathematicians, Madrid plex hair loss disorders with a major focus on the autoimmune Genet 92:81-87. interacting stochastic systems of many components. This disorder alopecia areata (AA). We have the largest sample 4. Jagielska D, Redler S, Brockschmidt FF, Herold C, Garcia includes a special focus on models from statistical mechan- Bartels N, Hanneken S, Eigelshoven S, Refke M, Barth S, Giehl 10 Most Relevant Publications for Prof. Anton Bovier of AA patients available worldwide, which includes a current ics with an emphasis on disordered models, in particular KA, Kruse R, Lutz G, Wolff H, Blaumeiser B, Böhm M, Blume-Pey- spin glasses. Apart from classical aspects of equilibrium 1. Bovier, A. and den Hollander, F. 2015 Metastability: A total of more than 2.200 individuals of middle European origin. tavi U, Becker T, Nöthen MM, Betz RC. 2012. A follow-up study of We have been able to demonstrate the contribution of the Gibbs measures I am particularly interested in aspects of Potential-Theoretic Approach. xxi + 581 pp. Grundlehren a genome-wide association scan in alopecia areata: replication of der mathematischen Wissenschaften Vol. 351, Springer, HLA-complex and the genes PTPN22, TRAF1/C5 , CTLA4, previously identified loci and identification of IL13 and KIAA0350 as long term dynamics such as metastability and aging. More IL13 and KIAA0350 to the disease risk using candidate gene new susceptibility loci supported with genome-wide significance. J recently I am also interested in application of methods from Charm. studies. By the use of genome-wide association studies, Invest Dermatol 132:2192-2197. these areas in models of population genetics, ecology, and 2. Mayer, H, Bovier, A. 2015. Stochastic models of T-cell meta-analyses, immunochips and functional studies, we just 5. Wen Y, Liu Y, Xu Y, Zhao Y, Hua R, Wang K, Sun M, Li Y, Yang neurodegenerative diseases. activation. J. Math. Biology 70: 99-132. recently identified HLA-DR as a key etiologic driver for AA as S, Zhang XJ, Kruse R, Cichon S, Betz RC, Nothen MM, van 3. Arguin, L-P, Bovier, A. Kistler, N. 2013. The extremal Steensel MA, van Geel M, Steijlen PM, Hohl D, Huber M, Dunnill process of branching Brownian motion. Prob. Theor. Rel. well as two loci outside the HLA-region: ACOXL/BCL2L11 and GS, Kennedy C, Messenger A, Munro CS, Terrinoni A, Hovnanian Education / Training GARP. Future analyses and functional studies will contribute to Fields: 157:535-574 . A, Bodemer C, de Prost Y, Paller AS, Irvine AD, Sinclair R, Green Technical University of Berlin, Germany a comprehensive understanding of AA. J, Shang D, Liu Q, Luo Y, Jiang L, Chen HD, Lo WH, McLean WH, 4. Hölzel, M, Bovier, A, Tüting, T. 2013. Plasticity of He CD, Zhang X. 2009. Loss-of-function mutations of an inhibitory Mathematics, Habilitation, 1995 tumor and immune cells: a source of heterogeneity and a Education / Training upstream ORF in the human hairless transcript cause Marie Unna The Swiss Federal Institute of Technology (ETH), Zurich cause for therapy resistance? Nature Reviews Cancer: 13: University of Bonn, Germany, Human Genetics, Habilitation, 2009 hereditary hypotrichosis. Nat Genet 41: 228-33. Physics, Dr. sc. nat., 1986 365—376. University of Bonn, Germany, Human Genetics, Medical 6. Pasternack SM, von Kugelgen I, Aboud KA, Lee YA, Rus- University of Bonn, Germany 5. Bovier, A, Gayrard V., Svejda, A. 2013. Convergence to Specialist, 2007 chendorf F, Voss K, Hillmer AM, Molderings GJ, Franz T, Ramirez Physics, Diploma, 1981 Karolinska Institute, Stockholm, Sweden University of Saarland A, Nurnberg P, Nothen MM, Betz RC. 2008. G protein-coupled extremal processes in random environments and applica- Clinical Medicine, Medical license, 1999 receptor P2Y5 and its ligand LPA are involved in maintenance of tions to extremal ageing in SK models. Probab Theor. Rel. human hair growth. Nat Genet 40: 329-34. Appointments / Positions Held University of Saarland, Germany, Medicine, MD thesis, 1998 Fields 157: 151–183. 7. Hillmer AM, Brockschmidt FF, Hanneken S, Eigelshoven S, 2008 - present 6. Arguin, L-P, Bovier, A, Kistler, N. 2011. The genealogy Appointments / Positions Held Steffens M, Flaquer A, Herms S, Becker T, Kortum AK, Nyholt DR, Zhao ZZ, Montgomery GW, Martin NG, Muhleisen TW, Alblas MA, Full Professor, Institute for Applied Mathematics of extremal particles of branching Brownian motion, Com- 2015 - present W2 Professorship, Institute of Human Genetics, Moebus S, Jockel KH, Brocker-Preuss M, Erbel R, Reinartz R, University of Bonn, Germany mun. Pure Appl. Math. 64: 1647--1676 University of Bonn, Germany Betz RC, Cichon S, Propping P, Baur MP, Wienker TF, Kruse R, 2003 - 2008 7. Bovier, A. 2006. Statistical mechanics of disordered 2010 - 2015 Heisenberg Professorship, Institute of Human Nothen MM. 2008. Susceptibility variants for male-pattern bald- Full Professor, Mathematics, Technical University, Berlin, systems. A mathematical perspective, 312 + xiv pp, Cam- Genetics, University of Bonn, Germany ness on chromosome 20p11. Nat Genet 40: 1279-81. Germany bridge Series in Statistical and Probabilistic Mathematics 2009 - 2010 Research Scientist, Institute of Human Genetics, 8. Betz RC, Planko L, Eigelshoven S, Hanneken S, Pasternack 1994 - 2008 University of Bonn, Germany SM, Bussow H, Van Den Bogaert K, Wenzel J, Braun-Falco M, Cambridge University Press Vol. 18 Laboratory Head, and 2nd Deputy Director 2004 - 2009 Independent Head of a Junior Research Group, Rutten A, Rogers MA, Ruzicka T, Nothen MM, Magin TM, Kruse 8. Bovier, A, Gayrard V, Klein M. 2005. Metastability in Institute of Human Genetics, University of Bonn, Germany R. 2006. Loss-of-function mutations in the keratin 5 gene lead to Weierstrass-Institute for Applied Analysis and Stochastics reversible diffusion processes II. precise asymptotics for Dowling-Degos disease. Am J Hum Genet 78: 510-9. 2002 - 2004 Postdoctoral fellow, Department of Medical (WIAS), Berlin small eigenvalues. J Europ Math Soc 7: 69–99 9. Levy-Nissenbaum E, Betz RC, Frydman M, Simon M, Lahat 1992 - 1995 9. Baake E, Baake M, Bovier, A, Klein M. 2005. An as- Genetics, University of Antwerp, Belgium H, Bakhan T, Goldman B, Bygum A, Pierick M, Hillmer AM, Jonca 2000 - 2002 Postdoctoral fellow, Institute of Human Genetics, N, Toribio J, Kruse R, Dewald G, Cichon S, Kubisch C, Guerrin M, Deputy Laboratory Head, WIAS, Berlin ymptotic maximum principle for essentially linear evolution University of Bonn, Germany Serre G, Nothen MM, Pras E. 2003. Hypotrichosis simplex of the 1991 - 1992 models. J Math Biology 50: 83–114 1999 - 2000 Research Scientist, Institute of Human Genetics, scalp is associated with nonsense mutations in CDSN encoding Research Associate, Mathematics Department, Bochum 10. Ben Arous G, Bovier, A, Gayrard V. 2003. Glauber University of Bonn, Germany corneodesmosin. Nat Genet 34: 151-3. University, Germany dynamics of the random energy model. 2. Aging below the 10. Betz RC, Schoser BG, Kasper D, Ricker K, Ramirez A, Stein V, 1988 - 1991 critical temperature. Commun. Math. Phys. 236: 1-54 Torbergsen T, Lee YA, Nöthen MM, Wienker TF, Malin JP, Propping Honors / Awards Research Associate, Physics Department University of 2010 - 2015 Heisenberg-Professorship from the DFG P, Reis A, Mortier W, Jentsch TJ, Vorgerd M, Kubisch C. 2001. Bonn, Germany 2004 - 2009 Emmy Noether Independent Junior Research Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease. Nat Genet 28: 218-9. 1986 - 1988 Group (DFG) 2008 PRO-SCIENTIA-Sponsorship Award of the Eckhart- Visiting Assistant Professor, Mathematics Department

178 179 1988 -1990 2005 - 2007 Research Fellow, Institute for Genetics, University of Postdoctoral Fellowship, German Academic Exchange Prof. Irmgard Förster, PhD Cologne Dr. Annett Halle, MD Foundation (DAAD) Life and Medical Sciences Institute (LIMES) center of advanced european studies and research (caesar) 2006 Honors / Awards Young Scientist Award, Science Foundation Berlin, 2016 - 2020 Member of the Scientific Committee of the Germany HZI (Helmholtz-Zentrum für Infektionsforschung GmbH) 2006 2016 - 2020 Member of the DFG Immunology Committee Award for the best medical dissertation of 2005, Berlin Since 06/2012 Society for Psychiatry and Neurology Leibniz Chair at the IUF Düsseldorf 2005 1994 Humboldt Prize (Prize for best dissertation of the year, Bennigsen Foerder Prize, Ministry of Science and Research Humboldt University Berlin) of North Rhine-Westphalia 1991 - 1992 10 Most Relevant Publications for Dr. Annett Halle Research grant from the DFG 1. Schnaars M, Beckert H, Halle A. Assessing β-amyloid- 1985 - 1988 induced NLRP3 inflammasome activation in primary microglia. Research Scholarship from the Fritz Thyssen Stiftung Methods Mol Biol. 2013;1040:1-8. 2. Krabbe, G.*, Halle, A.*, Matyash, V., Rinnenthal, J. L., 10 Most Relevant Publications for Prof. Irmgard Förster Eom, G. D., Bernhardt, U., Miller, K. R., Prokop, S., Ket- 1. Didiovic, S., Opitz, F.V., Holzmann, B., Förster, I., tenmann, H. and Heppner, F. L., Functional impairment of Rheinische Friedrich-Wilhelms-Universität Bonn Weighardt, H. 2015. Requirement of MyD88 signaling in kera- center of advanced european studies and microglia coincides with Beta-amyloid deposition in mice with Alzheimer-like pathology. PLoS One 2013. 8: e60921. Life and Medical Sciences Institute (LIMES), tinocytes for Langerhans cell migration and initiation of atopic research (caesar), Max Planck Research Group 3. Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Immunology and Environment, Director dermatitis-like symptoms in mice. Eur J Immunol. 2015 Dec 23 „Neuroimmunology“ 2. Globisch, T, Steiner, N*, Fülle, L*, Lukacs-Kornek, V, Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, E-Mail: [email protected] Degrandi, D, Dresing, P, Alferink, J, Lang, R, Pfeffer, K, Beyer, E-Mail: [email protected] A., Tzeng, T. C., Gelpi, E., Halle, A., Korte, M., Latz, E. and M., Weighardt, H, Kurts, C, Ulas, T, Schultze JL and Förster, I. Golenbock, D. T., NLRP3 is activated in Alzheimer‘s disease Research Expertise 2014. Cytokine-dependent regulation of denditic cell differen- Research Expertise and contributes to pathology in APP/PS1 mice. Nature 2013. Prof. Förster has special expertise in the functional tiation in the splenic microenvironment. Eur. J. Immunol. 44, Dr. Halle’s group studies innate immune mechanisms and 493: 674-678. 4. Stewart, C. R., Stuart, L. M., Wilkinson, K., van Gils, J. characterization of macrophages and dendritic cells using 500-510. microglial function in Alzheimer’s disease using cell culture M., Deng, J., Halle, A., Rayner, K. J., Boyer, L., Zhong, R., conditional gene targeting techniques. She is interested 3. Köhler, T, Reizis, B, Johnson, RS, Weighardt, H and techniques and mouse models of Alzheimer’s disease. Frazier, W. A., Lacy-Hulbert, A., El Khoury, J., Golenbock, D. T. in cell migration and immune regulation in barrier organs, Förster, I. 2012. Influence of hypoxia inducible factor 1a on dendritic cell differentiation and migration. Eur. J. Immunol. 42, and Moore, K. J., CD36 ligands promote sterile inflammation and has profound experience with mouse models of atopic Education / Training through assembly of a Toll-like receptor 4 and 6 heterodimer. dermatitis, inflammatory bowel disease and 1226-1236. 4. Stutte S, Quast T, Gerbitzki N, Savinko T, Novak N, Reifen- Charité – University Medicine Berlin, Nat Immunol 2010. 11: 155-161. bacterial infection. berger J, Homey B, Kolanus W, Alenius H and Förster I. 2010. Medical Neuroscience, MD thesis, 2005 5. Siednienko, J., Halle, A., Nagpal, K., Golenbock, D. T. Education / Training Requirement of CCL17 for CCR7- and CXCR4-dependent Free University Berlin, Humboldt University Berlin, and Miggin, S. M., TLR3-mediated IFN-beta gene induction is Clinical Medicine, MD, 2003 negatively regulated by the TLR adaptor MyD88 adaptor-like. University of Cologne, Germany, Genetics, PhD, 1988 migration of cutaneous dendritic cells. Proc. Natl. Acad. Sci. USA 107: 8736-41 . Eur J Immunol 2010. 40: 3150-3160. University of Marburg, Germany, Human Biology, Diploma, 5. Semmling V, Lukacs-Kornek V, Thaiss C, Quast T, Appointments / Positions Held 6. Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., 1985 Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, Hochheiser K, Panzer U, Rossjohn J, Perlmutter P, Cao J, 2011 - present Godfrey D, Savage P, Knolle P, Kolanus W, Förster, I* and K. J. and Golenbock, D. T., The NALP3 inflammasome is Appointments / Positions Held Max-Planck Research Group leader Kurts C*. 2010. Alternative cross-priming through CCL17/ involved in the innate immune response to amyloid-beta. Nat center of advanced european studies and research 2012 - present CCR4-mediated CTL attraction towards NKT cell-licensed Immunol 2008. 9: 857-865. W3 Professor of Immunology and Environment Life and dendritic cells. Nat. Immunol. 11: 313-20. (caesar), Bonn, Germany 7. Halle, A.*, Zhou, S*., Kurt-Jones, E. A., Cerny, A. M., Medical Sciences (LIMES) Institute, University of Bonn 6. Buch T, Polic B, Clausen BE, Weiss S, Akilli Ö, Chang 2009 - 2011 Porpiglia, E., Rogers, M., Golenbock, D. T. and Finberg, R. W., 2005 - 2012 CH, Flavell R, Schulz A, Jonjic S, Waisman A and Förster, I. Research fellow and resident in Neuropathology Lymphocytic choriomeningitis virus (LCMV) infection of CNS Laboratory Head of Molecular Immunology 2006. MHC class II expression through a hitherto unknown Department of Neuropathology, Charité – University glial cells results in TLR2-MyD88/Mal-dependent inflammatory IUF - Leibniz Institute for Environmental Medicine at the pathway supports T helper cell dependent immune responses: Medicine Berlin, Germany responses. J Neuroimmunol 2008. 194: 70-82. University of Düsseldorf, Germany implications for MHC class II deficiency. Blood. 107, 2005 - 2008 8. Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., 2004 - 2012 1434-1444. Postdoctoral fellow and instructor in Internal Medicine, Kono, H., Rock, K. L., Fitzgerald, K. A. and Latz, E., Silica C3 Professor of Molecular Immunology, Heinrich-Heine-Uni- 7. Alferink J*, Lieberam I*, Reindl W, Behrens A, Weiß S, Department of Infectious Diseases, University of crystals and aluminum salts activate the NALP3 inflammasome versity Düsseldorf Hüser N, Gerauer K, Ross R, Reske-Kunz A, Ahmad-Nejad Massachusetts, Worcester, USA through phagosomal destabilization. Nat Immunol 2008. 9: 847-856. 1998 - 2004 P, Wagner H and Förster, I. 2003. Compartmentalized 2003 - 2005 9. Jain, V., Halle, A., Halmen, K. A., Lien, E., Charrel-Dennis, Head of the Volkswagen Foundation Research Group production of CCL17 in vivo: strong inducibility in peripheral Medical dissertation and resident in Neurology, Department M., Ram, S., Golenbock, D. T. and Visintin, A., Phagocytosis Institute for Medical Microbiology, Immunology and Hygiene dendritic cells contrasts selective absence from the spleen. of Experimental Neurology, Charité – University Medicine J. Exp. Med. 197, 585-599. and intracellular killing of MD-2 opsonized gram-negative bac- and the second Medical Clinic, Technical University of Berlin, Germany teria depend on TLR4 signaling. Blood 2008. 111: 4637-4645. Munich 8. Lieberam I and Förster, I. 1999. The murine beta-chemo- 2000 kine TARC is expressed by subsets of dendritic cells and 10. Halle, A.*, Bermpohl, D.*, Freyer, D., Dagand, E., Braun, J. 1997 - 1998 Research internship, Department of Cell Biology, Harvard attracts primed CD4+ T cells. Eur. J. Immunol. 29: 2684-2694. S., Bechmann, I., Schroder, N. W. and Weber, J. R., Bacterial Assistant Professor, Institute for Genetics, University of University, Boston, USA 9. Clausen BE, Burkhardt C, Reith W, Renkawitz R and programmed cell death of cerebral endothelial cells involves Cologne Förster, I. 1999. Conditional gene targeting in macrophages dual death pathways. J Clin Invest 2005. 115: 1607-1615. 1993 - 1997 and granulocytes using LysMcre mice. Transg. Res. 8: 265- Honors / Awards *These authors contributed equally Postdoctoral Research Fellow, Institute for Genetics, 277. 2010 University of Cologne 10. Takeda K*, Clausen BE*, Kaisho T, Tsujimura T, Terada Ernst Jung-Career Award for Medical Research 1990 - 1993 N, Förster, I* and Akira S*. 1999. Enhanced Th1 activity and 2008 Postdoctoral Research Fellow, University of California, development of chronic enterocolitis in mice devoid of Stat3 in Lydia Rabinowitsch Fellowship for young scientists, Charité San Francisco, USA macrophages and neutrophils. Immunity. 10: 39-49. Berlin

*These authors contributed equally

180 181 Honors / Awards 2011 2014 - present Elected Member of the German Academy of Christa Lorenz Award for Amyotrophic Lateral Sclerosis Prof. Gunther Hartmann, MD Sciences Leopoldina Prof. Michael Heneka, MD Research Institute of Clinical Chemistry and Clinical Pharmacology 2012 Gottfried-Wilhelm Leibniz-Preis Clinical Neurosciences Unit 2010 - present 2011 - 2012 Elected President of the Oligonucleotide Therapeutics Editorial Board Journal of Neurochemistry Society (OTS) 2007 - present 2011 Dr.-Friedrich-Sasse-Preis, Berliner Medizinische Gesellschaft/ Board Member of the Competence Network Degenerative GoBio-Award of the Federal Ministry for Education and Research (BMBF) Dementias (CNDD) 2010 Elected Vice Speaker of the SFB 670 2008 2009 Elected member of the committee Krebstherapie-Studien of Editorial board, Journal of Chemical Neuroanatomy the German Cancer Aid (Deutsche Krebshilfe) 1998 2007 Wilhelm-Vaillant-Award for Medical Sciences Attempto Award - best Thesis of the University of Bonn 2004 Ludwig-Heilmeyer-Award (Ludwig-Heilmeyer Society, Internal Medicine, Germany) / Biofuture Award, of the Federal Ministry for 10 Most Relevant Publications for Prof. Michael Heneka Education and Research (BMBF) / Georg-Heberer Award, Chiles Foundation, Portland 1. Heneka MT, Klockgether T, Feinstein DL. Peroxisome 2000 Paul-Martini-Award / Award “Young Master” of the German proliferator-activated receptor-gamma ligands reduce Society for Hematology and Oncology neuronal inducible nitric oxide synthase expression and cell death in vivo. J Neurosci 2000;20:6862-6867. 10 Most Relevant Publications for Prof. Gunther Hartmann 2. Heneka MT, Galea E, Gavriluyk V, Dumitrescu-Ozimek 1. Herzner-AM, Hagmann CA, Goldeck M, Keßels S, Kübler K, L, Daeschner J, O´Banion MK, Klockgether T, Feinstein DL. Rheinische Friedrich-Wilhelms-Universität Bonn Wittmann S, Gramberg T, Andreeva L, Hopfner KP, Mertens C, Rheinische Friedrich-Wilhelms-Universität Bonn Noradrenergic depletion potentiates beta-amyloid induced Zillinger T, Jin T, Xiao TS, Bartok E, Coch C, Ackermann D, Hornung Institute of Clinical Chemistry and Clinical Pharmacology, V, Ludwig J, Barchet W, Hartmann G* and Schlee M*. Sequence- Clinical Neurosciences Unit, Director cortical inflammation: Implications for Alzheimer’s disease. Director specific activation of cGAS by Y-form DNA structures as found in E-Mail: [email protected] J Neurosci 2002;22:2434-2442. E-Mail: [email protected] primary HIV-1 cDNA. Nat Immunol 2015 Oct; 16(10): 1025-33. 3. Heneka MT, Dewachter I, Sastre M, Dumitrescu-Ozimek 2. Schuberth-Wagner C, Ludwig J, Bruder AK, Herzner AM, Zillinger L, Cuiperi K, a gonist pioglitazone and ibuprofen reduces Research Expertise Research Expertise T, Goldeck M, Schmidt T, Schmid-Burgk JL, Kerber R, Wolter S, inflammation and A 1-42 levels in APP V717I transgenic The focus of research is the immunorecognition of nucleic acids, and its β Stümpel JP, Roth A, Bartok E, Drosten C, Coch C, Hornung V, Prof. Heneka is involved in basic science and translational intersection with RNA interference. The group contributed to the mice. Brain 2005;128:1442-1453. Barchet W, Kümmerer BM, Hartmann G* and Schlee M*. A conserved research with focus on neurodegeneration and neuroinflam- immunobiology of TLR9 and CpG DNA, specifically the function of TLR9 4. Schütz B, Reimann J, Dumitrescu-Ozimek L, Kappes- histidine in RIG-I controls immune tolerance to N1-2’O-methylated mation. His major disease of interest and research topics in the human immune system. Furthermore, the group found that short Horn K, Landreth GE, Schürmann B, Zimmer A, Hene- self RNA. Immunity, 2015 Jul 21;43(1):41-51. include Alzheimer disease, amyotrophic lateral sclerosis, interfering RNA molecules (siRNA) activate TLR7, and worked on the 3. Goubau D, Schlee M, Deddouche S, Pruijssers AJ, Zillinger T, ka MT. The oral antidiabetic pioglitazone protects from structural requirements for the detection of RNA by TLR7 and TLR8. The septic encephalopathy and multiple sclerosis. In clinical Goldeck M, Schuberth C, Van der Veen AG, Fujimura T, Rehwinkel J, neurodegeneration and ALS-like symptoms in SOD1-G93A group identified the RNA ligand for RIG-I, and analyzed the signaling neurology, Prof. Heneka holds special expertise in neurode- Iskarpatyoti JA, Barchet W, Ludwig J, Dermody TS, Hartmann G, transgenic mice. J Neurosci 2005;25:7805-7812. pathways of RIG-I, and resolved the crytal structure or RIG-I bound to its generative and autoimmune CNS disorders. Reis e Sousa C. Antiviral immunity via RIG-I-mediated recognition of 5. Sastre M, Dewachter I, Rossner S, Bogdanovic N, ligand 5´-triphosphate RNA. The group identified cyclic [G(2‘,5‘)pA(3“,5”) RNA bearing 5’-diphosphates. Nature. 2014 Oct 16;514(7522):372-5 Rosen E, Borghraef P, Evert BO, Dumitrescu-Ozimek D, p] as the metazoan second messenger in the cGAS-STING pathway. 4. Gehrke N, Mertens C, Zillinger T, Wenzel J, Bald T, Zahn S, Tüting T, Education / Training The group applies immunostimulatory nucleic acids and siRNA for Thal DR, Landreth GE, Walter J, Klockgether T, Van Leuven Hartmann G, Barchet W. Oxidative damage of DNA confers resistance University of Bonn, Germany, Neurology, Professorial F, Heneka MT (2006) NSAIDs suppress BACE1 gene immunotherapy of cancer and viral infection. to cytosolic nuclease TREX1 degradation and potentiates STING- qualification (Habilitation), 2003 expression by the activation of PPARγ. Proc Natl Acad Sci Education / Training dependent immune sensing. Immunity 2013 Sep 19;39(3):482-95. University of Bonn, Germany, Neurology, Specialty 5. Gao P, Ascano M, Wu Y, Barchet W, Gaffney BL, Zillinger T, USA 2006;103:443-448. University of Munich, Germany, Experimental Pharmacology and qualification, 2002 Toxicology Degree, 2006 Serganov AA, Liu Y, Jones RA, Hartmann G, Tuschl T, Patel DJ. 6. Heneka MT, Ramanathan M, Jacobs AH, Dumitres- University of Munich, Germany, Clinical Pharmacology, Degree, 2003 Cyclic [G(2‘,5‘)pA(3“,5”)p] Is the Metazoan Second Messenger University of Tübingen, Germany, Medicine, MD, 1996 cu-Ozimek L, Debeir T, Sastre M, Bilkei-Gorzo A, Zimmer A, University of Munich, Germany, Clinical Pharmacology, Habilitation, Produced by DNA-Activated Cyclic GMP-AMP Synthase. Cell 2013 Galldiks N, Hoehn M, Heiss WD, Klockgether T, Staufenbiel 2001 May 23;153:1094-107. Appointments / Positions Held M. Locus ceruleus degeneration promotes Alzheimer University of Ulm, Germany, Clinical Genetics, MD thesis, 1994 6. Wang Y, Ludwig J, Schuberth C, Goldeck M, Schlee M, Li H, 2008 - present pathogenesis in APP transgenic mice. J. Neurosci Juranek S, Sheng G, Micura R, Tuschl T*, Hartmann G*, Patel DJ*. University of Ulm, Germany, Clinical Medicine, MD, 1993 Full Professor (W3) for Clinical Neurosciences, Head of the 2006;26:1343-1354. 2010. Structural and functional insights into 5‘-ppp RNA pattern Appointments / Positions Held 7. Weberpals M, Hermes M, Hermann M, Kummer MP, recognition by the innate immune receptor RIG-I. Nat Struct Mol Biol Clinical Research Group 177 of the DFG, University of Bonn 2014 Founder Rigontec GmbH, Rigontec GmbH, Bonn, Germany 17:781-7. 2004 - 2008 Terwel D, Semmler A, Berger M, Schäfers M, Heneka MT 2013 - present Vice Speaker of DZIF Bonn-Cologne, University of 7. Schlee M, Roth A, Hornung V, Hagmann CA, Wimmenauer V, Full Professor (C3) for Molecular Neurology, University of (2009) NOS2 gene deficiency protects from sepsis-induced Bonn, Germany Barchet W, Coch C, Janke M, Mihailovic A, Wardle G, Juranek S, Münster long-term cognitive deficits, J Neurosci, 29:14177-84. 2012 - present Speaker of the DFG-ImmunoSensation Cluster of Kato H, Kawai T, Poeck H, Fitzgerald KA, Takeuchi O, Akira S, Tuschl 8. Heneka MT, Nadrigny F, Regen T, Dumitrescu-Ozimek Excellence, University of Bonn, Germany 2004 T, Latz E, Ludwig J, Hartmann G. 2009. Recognition of 5‘ triphos- 2008 - present Head of Research Committee BONFOR, University of Senior Clinical Fellow in Neurology, University of Bonn L, Terwel D, Jardanhazi-Kurutz D, Walter J, Kirchhoff F, phate by RIG-I helicase requires short blunt double-stranded RNA as Bonn, Germany 1999 - 2003 Hanisch U, Kummer MP (2010) Locus ceruleus controls contained in panhandle of negative-strand virus. Immunity 31: 25-34. 2007 - present Full Professor and Chair, Institute of Clinical Chemistry Resident in Neurology, University of Bonn Alzheimer disease pathology by modulating microglial 8. Poeck H, Besch R, Maihoefer C, Renn M, Tormo D, Morskaya SS, and Clinical Pharmacology with the Central Laboratory of the functions through norepinephrine. Proc. Natl. Acad. Sci. Kirschnek S, Gaffal E, Landsberg J, Hellmuth J, Schmidt A, Anz D, 1996 - 1999 University Hospital, University of Bonn, Germany Bscheider M, Schwerd T, Berking C, Bourquin C, Kalinke U, Kremmer Resident in Neurology, University of Tübingen U.S.A., 107:6058-63. 2006 - present Member of the Steering Committee, E, Kato H, Akira S, Meyers R, Hacker G, Neuenhahn M, Busch D, 1992 - 1996 9. Kummer MP, Hermes M, Delekarte A, Hammerschmidt Comprehensive Cancer Center Köln-Bonn (CIO), University of Bonn, Ruland J, Rothenfusser S, Prinz M, Hornung V, Endres S, Tuting T, Predoctoral research fellow in the Dept. of Pharmacology, T, Kumar S, Terwel D, Walter J, Pape HC, König, S, Roeber 2005 Full Professor and Head, Division of Clinical Pharmacology, Hartmann G. 2008. 5‘-Triphosphate-siRNA: turning gene silencing University of Cologne S, Jessen F, Klockgether T, Korte M, Heneka MT (2011) University of Bonn, Germany and Rig-I activation against melanoma. Nat Med 14: 1256-63. Nitration of tyrosine 10 critically enhances amyloid β aggre- 2002 Assistant Professor, Division of Clinical Pharmacology, 9. Hornung V, Ellegast J, Kim S, Brzozka K, Jung A, Kato H, Poeck H, University of Munich, Germany Honors / Awards gation and plaque formation. Neuron 71:833-44. Akira S, Conzelmann KK, Schlee M, Endres S, Hartmann G. 2006. 10. Heneka MT, Kummer MP, Stutz A, Delekate A, 1999 - 2005 Research group: Therapeutic Oligonucleotides, 2013 - present 5‘-Triphosphate RNA is the ligand for RIG-I. Science 314: 994-7. Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, University of Munich, Germany 10. Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee Associate Editor Neurology, Neuroimmunology and 1998 - 1999 Postdoctoral Fellow, Department of Internal Medicine, Tzeng TC, Gelpi E, Halle A, Korte M, Latz E, Golenbock M, Uematsu S, Noronha A, Manoharan M, Akira S, de Fougerolles A, Neuroinflammation University of Iowa, USA DT (2013) NLRP3 is activated in Alzheimer‘s disease and Endres S, Hartmann G. 2005. Sequence-specific potent induction of 2013 1995 Research Fellow, Division of Clinical Pharmacology, University contributes to pathology in APP/PS1 mice. Nature. 493: IFN-alpha by short interfering RNA in plasmacytoid dendritic cells Hans und Ilse Breuer Award for Alzheimer Research of Munich, Germany through TLR7. Nat Med 11: 263-70. 674-678. 1994 Research Fellow, Department of Internal Medicine, University of 2012 - present Munich, Germany * These authors contributed equallly Editorial Board Molecular Neurobiology

182 183 1992 - 1994 Honors / Awards Prof. Michael Hoch, PhD Post-doc Fellow, Dept. Mol. Developmental Biology (Head: Prof. Achim Hörauf, MD 2015 Prof. H. Jäckle), Max Planck Institute for Biophysical Chemistry, The Innovation Award 2015 by BioRegionen Göttingen, Germany Life and Medical Sciences Institute (LIMES) Institute of Medical Microbiology, Immunology and Parasitology 2015 Memento Prize for Neglected Diseases Honors / Awards 2012 Since 2015 Rector of the University of Bonn President of the Paul Ehrlich Society for Chemotherapy e.V. 2006 - 2015 Managing Director of the LIMES (Life & Medical 2010 Sciences) Institute Coordinator for the partner BonnCologne, Dt. Zentrum für 2014 - 2015 Infektionsforschung (DZIF) – German Center for Infectious Member of the Academic Senate of the University of Bonn Disease. 2013 - 2015 2002 Member of the PhD fellowship selection committee of the Main annual award, German Society for Hygiene and German National Academic Foundation (Studienstiftung des Microbiology (DGHM) deutschen Volkes) 2001 2012 - 2015 Martini-Prize (bi-annual) for best clinical research of the Member of the Steering Committee of the ImmunoSensation University Clinic, Eppendorf/Hamburg Cluster of Excellence Bonn (German Research Foundation 1999 DFG) Main bi-annual award, German Society for Tropical 2009 - 2015 Medicine (DTG) Member of the Minerva Fellowship Committee of the Max Rheinische Friedrich-Wilhelms-Universität Bonn Rheinische Friedrich-Wilhelms-Universität Bonn Planck Society, Munich Life and Medical Sciences Institute (LIMES), Program 2006 - 2009 Institute of Medical Microbiology, Immunology and 10 Most Relevant Publications for Prof. Achim Hörauf Unit Genetics, Developmental Biology & Molecular Founding Head of the Section Molecular Biomedicine of the Parasitology, Director 1. Gondorf F, Berbudi A, Buerfent BC, Ajendra J, Bloem- Physiology Faculty for Mathematics & Natural Science, University of Bonn E-Mail: [email protected] ker D, Specht S, Schmidt D, Neumann AL, Layland LE, E-Mail: [email protected] 2005 - present Hoerauf A, Hübner MP. 2015 Chronic filarial infection Speaker of the Collaborative Research Centre SFB 645 Research Expertise provides protection against bacterial sepsis by functionally Research Expertise (German Research Foundation) Prof. Hörauf is internationally renowned for his work in Tropical reprogramming macrophages. PLoS Pathog. 2015 Jan Our aim is to identify new key regulators and genetic 2003 - 2004 Medicine, in particular for pioneering new drug treatments 22;11(1) networks which control metabolism and cell and organ Head of the Section Biology of the Faculty for Mathematics & against filariasis (a group of neglected tropical diseases). The 2. Mand S, Debrah AY, Klarmann U, Batsa L, Marfo-De- physiology. In particular, we elucidate the metabolism – Natural Science, University of Bonn new treatment exploits an endosymbiosis between worms brekyei Y, Kwarteng A, Specht S, Belda-Domene A, Fim- 2002 - 2004 innate immunity – gut microbiome axis, we investigate and bacterial endosymbionts called Wolbachia, which are mers R, Taylor M, Adjei O, Hoerauf A. 2012. Doxycycline Chairman of the Bonner Forum Biomedizin cellular (sphingo)lipid metabolism and body fat regulation, susceptible to some classes of antibiotics. Prof. Hörauf’s group improves filarial lymphedema independent of active filarial 2001 - 2004 infection: a randomized controlled trial. Clin Infect Dis. we study peroxisome and lysosome biogenesis and Speaker of the Research Unit FOR 425, funded by the DFG was the first to characterize a TLR2 ligand from Wolbachia 55:621-30. metabolic disorders (e.g. lipid storage diseases or neurode- 2000 - 2007 and established that blindness in onchocerciasis (or ‘river generation), and we analyse new regulators of cell-to-cell Member of the reviewer panel for the award of Post Graduate blindness’) is dependent on innate immune reactions against 3. Specht S, Frank JK, Alferink J, Dubben B, Layland LE, communication and tissue physiology. We use the fruit fly Fellowships of the DAAD (German Academic Exchange Wolbachia. They were the first to detect regulatory T cells in Denece G, Bain O, Förster I, Kirschning CJ, Martin C, Ho- Drosophila, the mouse and zebra fish as genetic model Service) humans in an infection. Modulation of host’s immune respons- erauf A. 2011. CCL17 controls mast cells for the defense organisms for our studies. 1996 es is another focus of Prof. Hörauf’s group, demonstrating that against filarial larval entry. J Immunol 186:4845-52. Gerhard Hess Young Investigator Award (DFG) filarial infection and filarial antigen treatment protects against 4. Taylor M, Hoerauf A, Bockarie M. 2010. Lymphatic Education / Training 1989 - 1992 type 1 diabetes onset and improves glucose tolerance during filariasis and onchocerciasis. Lancet 376: 1175-85. University of Munich, Germany, Developmental Biology PhD Fellowship of the Boehringer Ingelheim Fonds (Foundation obesity. Using expression quantitative trait loci analysis, the role 5. Hoerauf A. 2009. Mansonella perstans-the importance PhD, 1992 for Basic Research in Medicine) of genetic factors in modulating cellular responses (to filarial of an endosymbiont. N Engl J Med 361: 1502-4. 1986 - 1989 University of Heidelberg, Germany, Biology Undergraduate antigens) and eventually filariae-caused pathology development 6. Specht S, Hoerauf A. 2007. Does helminth elimination Member of the German National Academic Foundation (Dipl.), 1989 is currently investigated. promote or prevent malaria? Lancet 369: 446-7. (Studienstiftung des deutschen Volkes) 7. Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A. 2005. Macrofilaricidal activity after doxycy- Appointments / Positions Held Education / Training 5 Most Relevant Publications for Prof. Michael Hoch University of Erlangen, Germany, Clinical Immunology, MD, cline treatment of Wuchereria bancrofti: a double- blind, 2010 1. Mass E, Wachten D, Aschenbrenner AC, Voelzmann A, 1989 randomised placebo-controlled trial. Lancet 365: 2116-21. Visiting Research Professors, ASMeW Institute, Hoch M. 2014. Murine Creld1 controls cardiac development University of Erlangen, Germany, Duke University, USA and 8. Saint Andre A, Blackwell NM, Hall LR, Hoerauf A, Waseda University, Japan through activation of calcineurin/NFATc1 signaling. Develop- Brattig NW, Volkmann L, Taylor MJ, Ford L, Hise AG, Lass 2006 - present Galaway University, Ireland mental Cell 28, 711-726. DOI: 10.1016/j.devcel.2014.02.012. JH, Diaconu E, Pearlman E. 2002. The role of endosymbi- Managing Director of the LIMES Institute, Chair Molecular Clinical Immunology MD, with clinical rotations, 1989 2. Becker T, Loch G, Beyer M, Zinke I, Aschenbrenner AC, Developmental Biology, LIMES Institute, University of Bonn, otic Wolbachia bacteria in the pathogenesis of river Carrera P, Inhester T, Schultze JL, Hoch M. 2010. FOXO- Germany Appointments / Positions Held blindness. Science 295: 1892-5. dependent regulation of innate immune homeostasis. Nature 2000 - 2002 2003 - present 9. Hoerauf A, Mand S, Adjei O, Fleischer B, Buttner DW. 463: 369-73. Director, Institute of Animal Physiology, University of Bonn, Full Professor and Director, Institute for Medical 2001. Depletion of wolbachia endobacteria in Onchocerca 3. Bauer R, Voelzmann A, Breiden B, Schepers U, Farwanah Germany volvulus by doxycycline and microfilaridermia after ivermec- H, Hahn I, Eckardt F, Sandhoff K, Hoch M. 2009. Schlank, a Microbiology, Immunology and Parasitology, University 1999 - present tin treatment. Lancet 357: 1415-6. member of the ceramide synthase family controls growth and Hospital Bonn, Germany Full Professor, Chair of Molecular Developmental Biology 10. Hoerauf A, Volkmann L, Hamelmann C, Adjei O, body fat in Drosophila. EMBO J 28: 3706-3716. 2001 - 2003 LIMES Institute, University of Bonn, Germany Autenrieth IB, Fleischer B, Buttner DW. 2000. Endosymbi- 4. Behr M, Wingen C, Wolf C, Schuh R, Hoch M. 2007. Head, Department of Helminthology, Bernard Nocht 1996 Wurst is essential for airway clearance and respiratory-tube Institute for Tropical Medicine, Germany otic bacteria in worms as targets for a novel chemotherapy Habilitation in Developmental Genetics & Cell Biology size control. Nat Cell Biol 9: 847-53. 1995 - 2001 in filariasis. Lancet 355: 1242-3. Technical University of Braunschweig, Germany 5. Fuss B, Becker T, Zinke I, Hoch M. 2006. The cytohesin Independent Laboratory Head, Bernard Nocht Institute for 1994 - 1999 Steppke is essential for insulin signalling in Drosophila. Nature Tropical Medicine, Germany Group Leader, Dept. Mol. Developmental Biology 444: 945-8. 1990 - 1994 (Head: Prof. H. Jäckle), Max Planck Institute for Biophysical Fellow, Institute for Clinical Microbiology, Immunology and Chemistry, Göttingen, Germany Hygiene, University of Erlangen, Germany

184 185 2013 Honors / Awards Prof. Veit Hornung, MD Pettenkofer Prize of the Max von Pettenkofer Foundation Prof. Jörg C. Kalff, MD 2006 2010 Fellow of the American College of Surgeons (FACS) Gene Center and Department of Biochemistry Award for Basic Medical Research of the GlaxoSmithKline Department of Surgery 2003 Foundation Elected Speaker of the KFO 115 2010 2000 Paul-Martini-Prize of the Paul-Martini-Foundation Ferdinand Sauerbruch Award, Berlin, Germany 2009 2000 ERC Starting Grant Young Investigator Award, American Motility Society 2007 2000 Heinz Maier Leibnitz Prize of the German Research BONFOR Young Investigator Research Award Foundation 2006 10 Most Relevant Publications for Prof. Jörg C. Kalff Graduate-Scholarship of the Novartis-Foundation for 1. Pantelis D, Beissel A, Kahl P, Vilz TO, Stoffels B, Wehner Therapeutical Research S, Kalff JC. 2011. Colonic anastomotic healing in the con- 2002 text of altered macrophage function and endotoxemia. Int J Study Scholarship of the Munich-Harvard-Alliance Colorect Dis 26:737-46. 2000 - 2003 2. Engel DR, Koscielny A, Wehner S, Maurer J, Schumak Fellow of the German National Academic Foundation B, Limmer A, Sparwasser T, Hirner A, Knolle P, Kalff JC*, Kurts C* (*joined corresponding authorship). 2010. T helper 10 Most Relevant Publications for Prof. Veit Hornung Gene Center and Department of Biochemistry Lud- Rheinische Friedrich-Wilhelms-Universität Bonn type 1 memory cells disseminate postoperative ileus over wig-Maximilians-University Munich 1. Ablasser, A., J. L. Schmid-Burgk, I. Hemmerling, G. L. Department of Surgery, Director the entire intestinal tract. Nat Med. 16:1407-13. Rheinische Friedrich-Wilhelms-Universität Bonn Horvath, T. Schmidt, E. Latz and V. Hornung. Cell intrinsic E-Mail: [email protected] 3. Wehner S, Buchholz BM, Schuichtrup S, Rocke A, immunity spreads to bystander cells via the intercellular Institute of Molecular Medicine, Director Schaefer N, Lysson M, Hirner A, Kalff JC. 2010. Mechan- transfer of cGAMP Nature, 2013; 503:530-534. E-Mail: [email protected] ical strain and TLR4 synergistically induce cell-specific 2. Ablasser, A., M. Goldeck, T. Cavlar, T. Deimling, G. Witte, Research Expertise inflammatory gene expression in intestinal smooth muscle I. Rohl, K. P. Hopfner, J. Ludwig and V. Hornung. cGAS The focus of research are the immunological consequences Research Expertise produces a 2‘-5‘-linked cyclic dinucleotide second messenger of operative trauma and their recognition and regulation in cells and peritoneal macrophages. Am J Physiol Gastroin- Prof. Hornung has expertise in pattern recognition, innate that activates STING Nature, 2013; 498: 380-384. postoperative dysfunction of the gastrointestinal tract. The test Liver Physiol 299:G1187-97. immunology, macrophages, dendritic cells, RNA biology 3. Bartok, E., F. Bauernfeind, M. G. Khaminets, C. Jakobs, group described and elucidated the immunological patho- 4. Pantelis D, Kabba MS, Kirfel J, Kahl P, Wehner S, and genome engineering technologies. B. Monks, K. A. Fitzgerald, E. Latz and V. Hornung. iGLuc: a mechanism of postoperative ileus. Furthermore, the group Buettner R, Hirner A, Kalff JC. 2010. Transient periopera- luciferase-based inflammasome and protease activity reporter found that the gastrointestinal field effect - a panenteric tive pharmacologic inhibition of muscularis macrophages Education / Training Nat Methods, 2013; 10: 147-154. inflammation following localized abdominal surgery - is as a target for prophylaxis of postoperative ileus does not 4. Schmid-Burgk, J. L., T. Schmidt, V. Kaiser, K. Honing and V. affect anastomotic healing in mice. Surgery 148:59-70. University of Munich, Germany, Clinical Pharmacology MD mediated by an immunological response involving resident Hornung. A ligation-independent cloning technique for intestinal macrophages, mesenteric dendritic cells and 5. Wehner S, Straesser S, Vilz TO, Pantelis D, Sielecki T, thesis, 2004 high-throughput assembly of transcription activator-like effector memory TH1 cells. de la Cruz VF, Hirner A, Kalff JC. 2009. Inhibition of p38 University of Munich, LMU, including exchange rotations genes Nat Biotechnol, 2013; 31: 76-81. mitogen-activated protein kinase pathway as prophylaxis of at Harvard University, USA, and University of Zürich, 5. Duewell, P., H. Kono, K. J. Rayner, C. M. Sirois, G. Vladimer, Education / Training postoperative ileus in mice. Gastroenterology 136:619-29. Switzerland, Clinical Medicine, MD, 2003 F. G. Bauernfeind, G. S. Abela, L. Franchi, G. Nunez, M. 6. Wehner S, Behrendt FF, Lyutenski BN, Lysson M, Bauer Schnurr, T. Espevik, E. Lien, K. A. Fitzgerald, K. L. Rock, K. J. University of Bonn, Germany, Surgery, Habilitation, 1999 AJ, Hirner A, Kalff JC. 2007. Inhibition of macrophage Appointments / Positions Held Moore, S. D. Wright, V. Hornung* and E. Latz*. NLRP3 University of Aachen, Germany, Intensive Care , MD thesis, function prevents intestinal inflammation and postoperative since 2015 inflammasomes are required for atherogenesis and activated 1988 ileus in rodents. Gut 56:176-185. by cholesterol crystals Nature, 2010; 464: 1357-1361. Chair of Immunobiochemistry, Gene Center and Depart- University of Aachen, Germany, Clinical Medicine, MD, 7. Wehner S, Schwarz NT, Hundsdörfer R, Hierholzer C, 6. Ablasser, A., F. Bauernfeind, G. Hartmann, E. Latz, K. A. ment of Biochemistry, Ludwig-Maximilians-University 1987 Tweardy DJ, Billiar TR, Bauer AJ, Kalff JC. 2005. Induc- Fitzgerald and V. Hornung. RIG- I-dependent sensing of poly Munich tion of IL-6 within the rodent intestinal muscularis following (dA:dT) through the induction of an RNA polymerase III-tran- Appointments / Positions Held 2014 - 2015 scribed RNA intermediate Nat Immunol, 2009; 10: 1065-1072. intestinal surgical stress. Surgery 137:436-46. Director (W3) Institute of Molecular Medicine, University 7. Hornung, V., A. Ablasser, M. Charrel-Dennis, F. Bauern- 2010 - present 8. Schwarz NT, Kalff JC, Turler A, Speidel N, Grandis JR, Hospital, University of Bonn feind, G. Horvath, D. R. Caffrey, E. Latz and K. A. Fitzgerald. Full Professor and Head, Dept. of Surgery, University of Billiar TR, Bauer AJ. 2004. Selective jejunal manipulation 2008 - 2013 AIM2 recognizes cytosolic dsDNA and forms a caspase-1-acti- Bonn, Germany causes postoperative pan-enteric inflammation and dysmo- Professor of Clinical Biochemistry, Institute for Clinical vating inflammasome with ASC Nature, 2009; 458: 514-518. 2009 tility. Gastroenterology 126:159-69. Chemistry and Clinical Pharmacology, University of Bonn, 8. Hornung, V.*, F. Bauernfeind*, A. Halle, E. O. Samstad, H. Head, Division of Transplant Surgery, University of Bonn, 9. Kalff JC, Türler A, Schwarz NT, Schraut WH, Lee KKW, Germany Kono, K. L. Rock, K. A. Fitz- gerald and E. Latz. Silica crystals Germany Tweardy DJ, Billiar TR, Simmons RL, Bauer AJ. 2003. 2006 - 2008 and aluminum salts activate the NALP3 inflammasome through 2003 Intra-abdominal activation of a local inflammatory response Postdoctoral research fellow, Division of Infectious Diseases phagosomal destabilization Nat Immunol, 2008; 9: 847-856. Professor of Surgery, University of Bonn, Germany within the human muscularis externa during laparotomy. and Immunology, University of Massachusetts, USA 9. Hornung, V., J. Ellegast, S. Kim, K. Brzozka, A. Jung, H. 1999 - 2001 Ann Surg 237:301-15. 2005 - 2006 Kato, H. Poeck, S. Akira, K. K. Conzelmann, M. Schlee, S. Visiting Research Professor, Dept. of Medicine, University of 10. Schwarz NT, Engel BM, Eskandari M, Kalff JC, Grandis Group leader, Division of Clinical Pharmacology Endres and G. Hartmann. 5‘-Triphosphate RNA is the ligand Pittsburgh, USA JR, Bauer AJ. 2002. Lipopolysaccharide preconditioning University of Munich, Germany for RIG-I Science, 2006; 314: 994-997. 1995 - 1998 and cross-tolerance: the induction of protective mecha- 2003 - 2005 10. Hornung, V., M. Guenthner-Biller, C. Bourquin, A. Ablasser, Research Fellow, Department of Surgery, University of nisms for rat intestinal ileus. Gastroenterology 123:586-98. M. Schlee, S. Uematsu, A. Noronha, M. Manoharan, S. Akira, Research Fellow, Division of Clinical Pittsburgh, USA A. de Fougerolles, S. Endres and G. Hartmann. Sequence- Pharmacology, University of Munich, Germany 1995 specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7 Nat Med, 2005; Clinical Fellow, Department of Surgery, University of Bonn, Honors / Awards 11: 263-270. Germany 2015 1989 Elected EMBO Member *These authors contributed equally Resident, Department of Surgery, University of Bonn, 2015 Germany ERC Consolidator Grant

186 187 1987 1997 - 2002 Feodor-Lynen-Stipend at the Department of Medical Independent Group Leader, Center of Molecular Prof. U. Benjamin Kaupp, PhD Chemistry, University of Kyoto, Japan Prof. Percy Knolle, MD Biology Heidelberg (ZMBH), University of Heidelberg, Germany center of advanced european studies and research (caesar) 1985 - 1988 Institute of Molecular Immunology 1991 - 1997 Assistant Professor of Biophysics, University of Osnabrück Physician at the 1st Medical Department, University of Mainz, 1982 - 1985 Germany Hochschulassistent, University of Osnabrück 1990 - 1991 1981 Postdoctoral Fellow, BASF Bioresearch, Corporation, Postdoctoral Fellow, SUNY Stony Brook, USA Cambridge, USA Honors / Awards Honors / Awards 2001 2013 Member of the North Rhine-Westphalian Academy of Award by the Volkswagen Foundation (1.5 Million €) Sciences 2005 Member of the “German Academy of Sciences 10 Most Relevant Publications for Prof. Percy Knolle Leopoldina” 1. Beyer M, Abdullah Z, Chemnitz JM, Maisel D, Sander J, 1999 Novartis Lecture, University Regensburg Lehmann C, Thabet Y, Shinde PV, Schmidleithner L, Kohne M, 1999 Keynote lecturer on international conferences Trebicka J, Schierwagen R, Hofmann A, Popov A, Lang KS, Ox- 1994 Alcon Research Award enius A, Buch T, Kurts C, Heikenwalder M, Fatkenheuer G, Lang 1987 Feodor-Lynen-Fellowship PA, Hartmann P, Knolle PA*, Schultze JL*. Tumor-necrosis factor 1978 Member of the Academic Senate Technical University impairs CD4(+) T cell-mediated immunological control in chronic center of advanced european studies and research Berlin Technische Universität München (TU) viral infection. Nat Immunol 2016;17:593-603. (caesar), Molecular Sensory Systems, Scientific Institute for Molecular Immunology, Director 2. Bottcher JP, Beyer M, Meissner F, Abdullah Z, Sander J, Hochst Director and Head of Department 10 Most Relevant Publications for Prof. U. Benjamin Rheinische Friedrich-Wilhelms-Universität Bonn B, Eickhoff S, Rieckmann JC, Russo C, Bauer T, Flecken T, Giesen E-Mail: [email protected] Kaupp Institute of Molecular Medicine, Director (until 2012) D, Engel D, Jung S, Busch DH, Protzer U, Thimme R, Mann M, 1. Jansen V, Alvarez L, Balbach M, Strünker T, Hegemann E-Mail: [email protected] Kurts C, Schultze JL, Kastenmuller W, Knolle PA. Functional Research Expertise P, Kaupp UB, Wachten, D. 2015. Controlling fertilization classification of memory CD8(+) T cells by CX3CR1 expression. Nat Commun 2015;6:8306. and cAMP signaling in sperm by optogenetics. eLife 4 Research Expertise Biophysics of sensory systems. Physiology of receptors 3. Knolle PA, Thimme R. Hepatic Immune Regulation and its 10.7554/eLife.05161 and ion channels in cellular signaling. Cell motility and The focus of Prof. Knolle’s research group is on the molecular Involvement in Viral Hepatitis Infection. Gastroenterology 2014, chemotaxis. Development of chemical tools for kinetic 2. Seifert R, Flick M, Bönigk W, Alvarez L, Trötschel C, and cellular mechanisms governing local immune control in 146: 1193-207 techniques in cell biology. Poetsch A, et al. 2015. The CatSper channel controls che- tissues. In his laboratory the relevance of local antigen presen- 4. Wolf MJ, Adili A, Piotrowitz K, Abdullah Z, Boege Y, Stemmer K, mosensation in sea urchin sperm. EMBO J. 34:379-392. tation by organ-resident liver cells was demonstrated for induc- Ringelhan M, Simonavicius N, Egger M, Wohlleber D, Lorentzen A, Education / Training 3. Alvarez L, Dai L, Friedrich BM, Kashikar ND, Gregor I, tion of immune tolerance in naïve CD4 and CD8 T cells. The Einer C, Schulz S, Clavel T, Protzer U, Thiele C, Zischka H, Moch Pascal R, Kaupp UB. 2012 The rate of change in Ca2+ development of novel cell separation techniques allowed to University of Osnabrück, Biophysics, Habilitation, 1983 H, Tschop M, Tumanov AV, Haller D, Unger K, Karin M, Kopf M, concentration controls sperm chemotaxis J. Cell. Biol. 196, study the mechanisms and functional relevance of different liver Knolle PA*, Weber A*, Heikenwalder M*. Metabolic Activation of Technical University of Berlin, Chemistry, PhD, 1979 653-663 cell populations at a new level of resolution and to compare the Intrahepatic CD8(+) T Cells and NKT Cells Causes Nonalcoholic University of Tübingen and Technical University of Berlin 4. Strünker T, Goodwin N, Brenker C, Kashikar ND, Wey- immune function of these non-professional antigen presenting Steatohepatitis and Liver Cancer via Cross-Talk with Hepatocytes. Chemistry, Diploma, 1974 and I, Seifert R, Kaupp UB. 2011. The CatSper channel cells with myeloid professional antigen presenting cells such Cancer Cell 2014;26:549-64. mediates progesterone-induced Ca2+ influx in human as dendritic cells or macrophages. His group has discovered 5. Böttcher JP, Schanz O, Garbers C, Zaremba A, Hegenbarth Appointments / Positions Held sperm. Nature novel stimulatory pathways that are initiated by unique immune S, Kurts C, Beyer M, Schultze JL, Kastenmuller W, Rose-John S, sensory mechanisms in liver-resident antigen presenting cells 2010 - 2011 471: 382-386 Knolle PA. IL-6 trans-Signaling-Dependent Rapid Development of that trigger local T cell immunity in the liver. The lab has devel- Director of the Max-Planck-Institute for Neurological 5. Schröder-Lang S, Schwärzel M, Seifert R, Strünker T, Cytotoxic CD8(+) T Cell Function. Cell Reports 2014;8:1318-27 oped an interest in local mechanisms determining regulation of Research, University of Cologne, Germany 6. Huang LR, Wohlleber D, Reisinger F, Jenne CN, Cheng RL, Kateriya S, Looser J, Watanabe M, Kaupp UB, Hegemann CD4 T cell differentiation with particular reference to the impact 2008 - present P, Nagel G. 2007. Fast manipulation of cellular cAMP level Abdullah Z, Schildberg FA, Odenthal M, Dienes HP, van Rooijen N, of nuclear receptors that also impact on the metabolic state of Schmitt E, Garbi N, Croft M, Kurts C, Kubes P, Protzer U, Heiken- Professor of Molecular Neurobiology, University of Bonn, by light in vivo. Nat. Methods 4: 39-42 T cells. walder M, Knolle PA. Intrahepatic myeloid-cell aggregates enable Germany 6. Strünker T, Weyand I, Bönigk W, Van Q, Loogen A, local proliferation of CD8(+) T cells and successful immunotherapy 2008 - present Brown JE, Kashikar ND, Hagen V, Krause E, Kaupp UB. Education / Training against chronic viral liver infection. Nat Immunol 2013;14:574-83. Scientific Director of caesar and Head of Department 2006. A K+-selective cGMP-gated ion channel controls 7. Böttcher JP, Schanz O, Wohlleber D, Abdullah Z, Debey-Pas- Molecular Sensory Systems, Center of Advanced European chemosensation of sperm. Nat Cell Biol 8: 1149-54 University of Mainz, Germany, Internal Medicine Specialist, 1997 cher S, Staratschek-Jox A, Hochst B, Hegenbarth S, Grell J, Lim- Studies and Research 7. Kaupp UB, Solzin J, Hildebrand E, Brown JE, Helbig A, German Cancer Research Centre, Heidelberg, Applied mer A, Atreya I, Neurath MF, Busch DH, Schmitt E, van Endert P, 2007 - present Hagen V, Beyermann M, Pampaloni F, Weyand I. 2003. The Immunology, MD thesis, 1990 Kolanus W, Kurts C, Schultze JL, Diehl L, Knolle PA. Liver-Primed Scientific Member of the Max-Planck-Society, signal flow and motor response controling chemotaxis of Universities of Frankfurt, Paris, Birmingham Memory T Cells Generated under Noninflammatory Conditions Max-Planck-Society sea urchin sperm. Nat Cell Biol 5: 109-17 (UK), Strasbourg, and Geneva, Medicine, MD, 1988 Provide Anti-infectious Immunity. Cell Reports 2013;3:779-95. 2000 - present 8. Körschen HG, Beyermann M, Müller F, Heck M, Vantler 8. Abdullah Z, Schlee M, Roth S, Mraheil MA, Barchet W, Bottcher Whitman Investigator, Marine Biological Laboratory (MBL), J, Hain T, Geiger S, Hayakawa Y, Fritz JH, Civril F, Hopfner KP, M, Koch KW, Kellner R, Wolfrum U, Bode C, Hofmann KP, Appointments / Positions Held Woods Hole, USA Kaupp UB. 1999. Interaction of glutamic-acid-rich proteins Kurts C, Ruland J, Hartmann G, Chakraborty T, Knolle PA. RIG-I 2013 - present 1988 - present with the cGMP signalling pathway in rod photoreceptors. detects infection with live Listeria by sensing secreted bacterial Director Institute of Molecular Immunology, TU Munich Professor of Biophysical Chemistry, University of Cologne, Nature 400: 761-6 nucleic acids. EMBO J 2012;31:4153-64. 2013 - 2017 Germany 9. Wohlleber D, Kashkar H, Gartner K, Frings MK, Odenthal M, 9. Gauss R, Seifert R, Kaupp UB. 1998. Molecular iden- coopted Medical Faculty, University of Bonn, Germany 2006 - 2009 Hegenbarth S, Borner C, Arnold B, Hammerling G, Nieswandt tification of a hyperpolarization- activated channel in sea 2006 - 2012 Director of the International Helmholtz Research urchin sperm. Nature 393: 583-7 B, van Rooijen N, Limmer A, Cederbrant K, Heikenwalder M, Vice-speaker of the SFB 704, University of Bonn, Germany Pasparakis M, Protzer U, Dienes HP, Kurts C, Kronke M, Knolle School of Biophysics and Soft Matter , Research Centre 10. Kaupp UB, Niidome T, Tanabe T, Terada S, Bönigk W, 2002 - 2012 PA. TNF-Induced Target Cell Killing by CTL Activated through Jülich Stühmer W, Cook NJ, Kangawa K, Matsuo H, Hirose T, Director Institute of Molecular Medicine, University of Bonn, Cross-Presentation. Cell Reports 2012;2:478-87. 1988 - 2007 et al. 1989. Primary structure and functional expression Germany 10. Protzer U, Maini MK, Knolle PA. Living in the liver: hepatic Director at the Institute of Neuroscience and Biophysics from complementary DNA of the rod photoreceptor cyclic 2002 infections. Nat Rev Immunol 2012;12:201-13. Research Centre Jülich GMP-gated channel. Nature 342: 762-6 Professor of Molecular Medicine and Immunology, University of Bonn, Germany

188 189 2007 tion/Nephrology US Patent 20070287153 - Methods for identification and 2014 Prof. Waldemar Kolanus, PhD validation of functional intracellular targets with intramers or in Prof. Christian Kurts, MD Elected member German National Academy of Sciences Life and Medical Sciences Institute (LIMES) vivo selection Institute of Experimental Immunology Leopoldina 2004 2012 US Patent 20040170990 - Intracellular nucleic acid inhibitors Gottfried-Wilhelm-Leibniz-Prize of the DFG of small guanine nucleotide exchange factors 2010 US Patent 20040029775 - Methods and compounds for Hans-U.-Zollinger-Award of the German Society for influencing beta3-integrin- dependent intracellular processes Nephrology 2003 2000 US Patent 20030138410 - Targeted cytolysis of HIV-infected Heisenberg-Fellowship of the cells by chimeric CD4 receptor-bearing cells Deutsche Forschungsgemeinschaft 2002 1999 US Patent 20020176851 - Redirection of cellular immunity by Sir Hans Krebs award for basic medical research protein-tyrosine kinase chimeras 1992 1996 Annual award of the German Society of Nephrology for best US Patent 6573362 - Cytohesin-PH peptides that affect the doctoral thesis ability of integrins to adhere 1986 - 1991 1994 Fellowship Studienstiftung des deutschen Volkes (German Munich Gene Center Junior Group Leader 5-year-Award, National Academic Foundation) BMBF and University of Munich Rheinische Friedrich-Wilhelms-Universität Bonn Rheinische Friedrich-Wilhelms-Universität Bonn 10 Most Relevant Publications for Prof. Christian Kurts Life and Medical Sciences Institute (LIMES), Molecular 10 Most Relevant Publications for Prof. Waldemar Institute of Experimental Immunology, Director 1. Schiwon M, Weisheit C, Franken L, Gutweiler S, Dixit A, Immunology & Cell Biology, Director Kolanus E-Mail: [email protected] Meyer-Schwesinger C, Pohl J, Maurice NJ, Thiebes S, Lorenz 1. Bald T, Quast T, Landsberg J, Rogava M, Glodde N, Lopez- K, Quast T, Fuhrmann M, Baumgarten G, Lohse MJ, Opdenak- E-Mail: [email protected] Ramos D, Kohlmeyer J, Riesenberg S, van den Boorn- Research Expertise ker G, Bernhagen J, Bucala R, Panzer U, Kolanus W, Gröne Konijnenberg D, Hömig-Hölzel C, Reuten R, Schadow B, HJ, Garbi N, Kastenmüller W, Knolle PA, Kurts C*, Engel DR*. Prof. Kurts and his group are interested in the mechanisms Research Expertise Weighardt H, Wenzel D, Helfrich I, Schadendorf D, Bloch W, 2014. Crosstalk between sentinel and helper macrophages governing antigen-presentation and the ensuing immune Prof. Kolanus and his group are interested in intracellular Bianchi M.E, Lugassy C, Barnhill RL, Koch M, Fleischmann BK, permits neutrophil migration into infected uroepithelium. Cell, response in the defense against infections and in immune- Förster I, Kastenmüller W, Kolanus W, Hölzel M, Gaffal E, Tüting T. 156:456–68, (*joint senior authorship) signal transduction events which control leukocyte adhe- mediated disease. Their main research projects focus on the 2014.Ultraviolet-radiation-induced inflammation promotes angiot- 2. Kastenmüller W, Kastenmüller K, Kurts C, Seder RA. sion, migration, and effector functions. The main emphasis ropism and metastasis in melanoma. Nature. 507,109-13. mechanisms of antigen cross-presentation to cytotoxic CD8 Dendritic Cell Targeted Vaccines - Hype or Hope? 2014. Nat of their current research activities lies in elucidating the 2. Müller S, Quast T, Schröder A, Hucke S, Klotz L, Jantsch J, T cells, peripheral immune tolerance of T and B lymphocytes Rev Immunol, 14(10):705-11 role of integrin adhesion receptors and the cytoskeleton in Gerzer R, Hemmersbach R, Kolanus W. Salt-dependent chemo- against self antigens, and the role of dendritic cells in diseases, 3. Kurts C, Panzer U, Anders HJ, Rees A. 2013. The immune the functional adaptation of leukocyte motility to specific taxis of macrophages. 2013 PLoS One. 16 :e73439. especially in kidney disease. microenvironments, some of which include force- 3. Ulbricht A, Eppler FJ, Tapia VE, van der Ven PF, Hampe N, system and kidney disease: basic concepts and clinical impli- dependent slow migration of immune cells on and across Hersch N, Vakeel P, Stadel D, Haas A, Saftig P, Behrends C, Fürst cations. Nat Rev Immunol, 13(10):738-53. Education / Training 4. Hochheiser K, Heuser, C Krause TA, Teteris S, Ilias A, barriers, versus force-independent, fast migration in the DO, Volkmer R, Hoffmann B, Kolanus W, Höhfeld J. University of Göttingen, Germany Weisheit C, Hoss F, Tittel AP, Panzer U, Knolle PA, Engel DR, interstitium. Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy., Curr Biol., 2013, 23, 430-435. Medicine MD, 1991 Tharaux PL, Kurts C. 2013. Exclusive CX3CR1-dependence 4. Quast T, Eppler F, Semmling V, Schild C, Homsi Y, Levy S, of kidney cortex dendritic cells identifies a therapeutic target in Education / Training Lang T, Kurts C, Kolanus W. CD81 is essential for the formation of Appointments / Positions Held glomerulonephritis. J Clin Invest, 123(10):4242-54. University of Hannover, Molecular Biology, PhD, 1987 membrane protrusions and regulates Rac1-activation in adhesion- 2015 Speaker GRK 2168 Bo&Merang (Bonn & Melbourne 5. Gottschalk C, Damuzzo V, Gotot J, Kroczek R, Yagita H, University of Hannover, Biology, Chemistry, State dependent immune cell migration., Blood, 2011, 118, 1818-1827. Research and Graduate training Group) Murphy KM, Knolle PA, Ludwig-Portugall I, Kurts C. 2013. 5. Loer B, Bauer R, Bornheim R, Grell J, Kremmer E, Kolanus examination, 1984 2013 Co-speaker SFB 704 “Molecular Mechanisms and Batf3-dependent renal lymph node DCs maintain immune-ho- W, Hoch M. 2008. The NHLdomain protein Wech is crucial for the Chemical Modulation of Local Immune Regulation“ University meostasis against circulating antigens; J Am Soc Nephrol, integrin-cytoskeleton link. Nat Cell Biol 10: 422-8. Appointments / Positions Held of Bonn, Germany 24:543-9. 6. Hafner M, Schmitz A, Grune I, Srivatsan SG, Paul B, Kolanus 6. Gotot J, Gottschalk C, Leopold S, Knolle PA, Yagita H, W, Quast T, Kremmer E, Bauer I, Famulok M. 2006. Inhibition of 2012 Co-speaker SFB TR57 “Organ-Fibrosis”, representing the 2002 - present Kurts C*, Ludwig-Portugall I*. 2012. Direct PD-1-mediated cytohesins by SecinH3 leads to hepatic insulin resistance. Nature Bonn site, University of Bonn, Germany Full Professorship, Molecular Immunology, suppression of autoreactive B cells by regulatory T cells. PNAS University of Bonn 444: 941-4. 2009 - present Director Institute of Experimental Immunology, 7. Shamri R, Grabovsky V, Gauguet JM, Feigelson S, Manevich University of Bonn, Germany 109(26):10468-7. (*joint senior authorship) 1999 - 2002 7. Tittel AP, Heuser C, Ohliger C, Yona S, Hämmerling GJ, Associate Professor, Biochemistry, E, Kolanus W, Robinson MK, Staunton DE, von Andrian UH, Alon 2003 - 2008 Full Professor of Molecular Immunology University R. 2005. Lymphocyte arrest requires instantaneous induction of an of Bonn, Germany Engel DR, Garbi N, Kurts C. 2012. Functionally relevant neu- University of Munich (LMU) trophilia in CD11c-diphteria toxin receptor transgenic mice. Nat 1999 extended LFA-1 conformation mediated by endothelium- bound 2002 Visiting scientist, Stephen Schoenberger Group chemokines. Nat Immunol 6: 497-506. Methods 9(4):385-90. Habilitation in Biochemistry, Faculty of Chemistry, University of La Jolla Institute for Allergy and Immunology, CA, USA 8. Boehm T, Hofer S, Winklehner P, Kellersch B, Geiger C, 2000 - 2003 Research group leader, Dept. of Nephrology and 8. Engel DR, Koscielny A, Wehner S, Maurer J, Schiwon M, Munich (LMU) Trockenbacher A, Neyer S, Fiegl H, Ebner S, Ivarsson L, Schneider Schumak B, Limmer A, Sparwasser T, Hirner A, Knolle PA, 1994 - 1999 Clinical Immunology, University of Aachen, Germany R, Kremmer E, Heufler C,Kolanus W. 2003. Attenuation of cell 1998 - 2000 Medical Officer and Research Fellow, Hannover Kalff JC, Kurts C. 2010. Th1 memory cells disseminate post- Independent Group Leader, Gene Center Munich, University of adhesion in lymphocytes is regulated by CYTIP, a protein which operative ileus over the entire intestinal tract. Nat Med, 16(12): Munich (LMU) Medical School, Germany mediates signal complex sequestration. EMBO J 22: 1014-24. 1997 - 1998 Postdoctoral Research Fellow, Dept of Microbiol- 1407–1413. 1990 - 1993 9. Geiger C, Nagel W, Boehm T, van Kooyk Y, Figdor CG, ogy, Monash Medical School, Melbourne, Australia 9. Semmling V, Lukacs-Kornek V, Thaiss CA, Quast T, Hoch- Post-doc Fellow, Molecular Immunology, Harvard Medical Kremmer E, Hogg N, Zeitlmann L, Dierks H, Weber KS, Kolanus 1995 - 1997 Postdoctoral Research Fellow, Thymus Biology heiser K, Panzer U, Rossjohn J, Perlmutter P, Cao J, Godfrey School W. 2000. Cytohesin-1 regulates beta-2 integrin-mediated adhesion DI, Savage PB, Knolle PA, Kolanus W, Forster I, Kurts C. 1988 - 1990 Post-doc Fellow, Immunology, Hannover Medical through both ARF-GEF function and interaction with LFA-1. EMBO Unit, The Walter and Eliza Hall Institute for Medical Research (WEHI), Melbourne, Australia 2010. Alternative cross-priming through CCL17-CCR4-me- School J 19: 2525-36. diated attraction of CTLs toward NKT cell-licensed DCs. Nat 10. Kolanus W, Nagel W, Schiller B, Zeitlmann L, Godar S, 1991 - 1995 Medical Officer and Research Fellow, Hannover Immunol 11: 313-20. Stockinger H, Seed B. 1996. Alpha L beta 2 integrin/LFA-1 binding Medical School, Germany Honors / Awards 10. Kurts C, Robinson BW, Knolle PA. 2010. Cross-priming in to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory health and disease. Nat Rev Immunol 10: 403-14. 2009 molecule. Cell 86: 233-42. Honors / Awards US Patent 20090105286, Low molecular inhibitors of cyohesin-family guanine nucleotide exchange factors 2016 *These authors contributed equally Elected member DFG Fachkollegium (Review Board) Inflamma-

190 191 Honors / Awards 2003 - 2008 2015 Head of the Scientific Advisory Board of the Max-Planck-Insti- Editorial Board member of ‚Stem Cells‘ Prof. Eicke Latz, MD PhD tute for Infection Biology in Berlin Prof. Harald Neumann, MD 2007 Institute of Innate Immunity 2015 Highly Cited Researcher in Immunology Institute of Reconstructive Neurobiology DANA-Foundation-Award, Neuroimmunology-Program 2015 Listed in the ‘World’s Most Influential Scientific Minds’ 1996 2014 Highly Cited Researcher in Immunology PCR-Award Boehringer Mannheim 2014 Listed in the ‘World’s Most Influential Scientific Minds’ 1992 2014 Kavli Fellow of the United States National Academy of Sciences (NAS) Research scholarship (German science foundation) 2013 ERC Consolidator Grant 10 Most Relevant Publications for Prof. Harald Neumann 10 Most Relevant Publications for Prof. Eicke Latz 1. Bodea LG, Wang Y, Linnartz-Gerlach B, Kopatz J, 1. Zimmer S, Grebe A, Bakke S, Bode N, Halvorsen B, Ulas T, Sinkkonen L, Musgrove R, Kaoma T, Muller A, Vallar L, Skjelland M, De Nardo D, Labzin L, Kerksiek A, Hempel C, Heneka Di Monte DA, Balling R and Neumann H. (2014). Neurode- M, Hawxhurst V, Fitzgerald M, Trebicka J, Björkhem I, Gustafsson generation by activation of the microglial complement- JA, Westerterp M, Tall AR, Wright SA, Espevik T, Schultze JL, phagosome pathway. J Neurosci. 2014 Jun Nickenig G, Lütjohann D, Latz E. Cyclodextrin promotes athero- 18;34(25):8546-56. sclerosis regression via macrophage reprogramming. Science 2. Neumann H. and Daly MJ. (2013). Variant TREM2 as Translational Medicine, April 2016, 6;8 (333) 2. Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, risk factor for Alzheimer’s disease. N Engl J Med. 2013 Jan Engels G, Brenker C, Nordhoff M, Mirandola SR, Al-Amoudi A, 10;368(2):182-4. Rheinische Friedrich-Wilhelms-Universität Bonn Mangan MS, Zimmer S, Monks BG, Fricke M, Schmidt RE, Espevik Rheinische Friedrich-Wilhelms-Universität Bonn 3. Claude J, Linnartz-Gerlach B, Kudin AP, Kunz WS and Institute of Innate Immunity, Director T, Jones B, Jarnicki AG, Hansbro PM, Busto P, Marshak-Rothstein Institute of Reconstructive Neurobiology Neumann H. (2013). Microglial CD33-related Siglec-E A, Hornemann S, Aguzzi A, Kastenmüller W & Latz E. The adaptor E-Mail: [email protected] E-Mail: [email protected] inhibits neurotoxicity by preventing the phagocytosis ASC has extracellular and ‘prionoid’ activities that propagate associated oxidative burst. J. Neurosci. 33(46):18270-6. Research Expertise inflammation. Nat Immunol, 2014, Aug;15(8):727-37 4. Zhang B*, Gaiteri C*, Bodea LG*, Wang Z, McElwee 3. De Nardo D*, Labzin LI*, Kono H, Seki R, Schmidt SV, Beyer Research Expertise The Latz Lab has a longstanding interest in deciphering the M, Xu D, Zimmer S, Lahrmann C, Schildberg FA, Vogelhuber J, J, Podtelezhnikov AA, Zhang C, Xie T, Tran L, Dobrin R, molecular mechanisms of innate immune receptor activation. In Neuroinflammation, mechanisms of inflammatory neurode- Kraut M, Ulas T, Kerksiek A, Krebs W, Bode N, Grebe A, Fitzgerald Fluder E, Clurman B, Melquist S, Narayanan M, Suver C, particular, the lab is interested in understanding how innate recep- generation, microglia-neuron interaction, Siglecs ML, Hernandez NJ, Williams BR, Knolle P, Kneilling M, Rocken M, Shah H, Mahajan M, Gillis T, Mysore J, MacDonald ME, tors interact with their ligands and how this molecular interaction Lutjohann D, Wright SD, Schultze JL* and Latz E*. (2014). leads to receptor activation. Recently, we have also focused on the Lamb JR, Bennett DA, Molony C, Stone DJ, Gudnason molecular details of the mechanisms that lead to the activation of High-density lipoprotein mediates anti-inflammatory reprogramming Education / Training V, Myers AJ, Schadt EE, Neumann H, Zhu J, Emilsson of macrophages via the transcriptional regulator ATF3. Nat the NLRP3 and AIM2 inflammasome. The NLRP3 inflammasome Technical University Munich, Germany, Habilitation in Neu- V. (2013). Integrated systems approach identifies genetic can respond to a broad range of cellular stressors and to sub- Immunol, 15(2), 152-160. nodes and networks in late-onset Alzheimer’s disease. Cell. stances that indicate metabolic derangements such as aggregated 4. Heneka MT*, Kummer MP, Stutz A, Delekate A, Schwartz S, roimmunology, 1998 Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, Gelpi E, University (FernUniversität) of Hagen, Germany, Business 2013 Apr 25;153(3):707-20. peptides, crystals of monosodium urate (forming in gout) or crys- 5. Wang Y, Neumann H. 2010. Alleviation of neurotoxicity tals of cholesterol that are found in atherosclerotic plaques. One Halle A, Korte M, Latz E* and Golenbock DT*. (2013). NLRP3 is Administration, 1994 goal of the research is to translate the molecular understanding of activated in Alzheimer’s disease and contributes to pathology in University of Würzburg and University of Munich (LMU), by microglial human Siglec-11. J Neurosci 30: 3482-8 innate immune receptor activation into the generation of molecular APP/PS1 mice. Nature, 493(7434), 674-678. Germany, Medicine, MD Thesis, 1991 6. Beutner C, Roy K, Linnartz B, Nappoli I, Neumann H. tools that could lead to the development of specific diagnostics 5. Duewell P*, Kono H*, Rayner KJ, Sirois CM, Vladimer G, 2010. Generation of microglial cells from mouse embryonic for inflammatory materials. Another goal is to devise means to Bauernfeind FG, Abela GS, Franchi L, Nunez G, Schnurr M, stem cells. Nature Protocols: 5:1481-94 Appointments / Positions Held pharmacologically interfere with the activation of innate immune re- Espevik T, Lien E, Fitzgerald KA, Rock KL, Moore KJ, Wright SD, 7. Takahashi K, Prinz M, Stagi M, Chechneva O, Neu- ceptors in order to develop novel approaches to treat inflammatory Hornung V* and Latz E*. (2010). NLRP3 inflammasomes are 2004 - present mann H. 2007. TREM2-transduced myeloid precursors diseases such as Alzheimer’s disease or atherosclerosis. required for atherogenesis and activated by cholesterol crystals. Head of the Neural Regeneration Group, University of mediate nervous tissue debris clearance and facilitate Nature, 464(7293), 1357-1361. Bonn, Germany Education / Training 6. Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, recovery in an 2001 - 2004 Humbolt University of Berlin, Germany, PhD, 2001 Horvath G, Caffrey DR, Latz E* and Fitzgerald KA*. (2009). AIM2 animal model of multiple sclerosis. PLoS Med 4: e124 Head of the Neuroimmunology Group European Free University of Berlin, Germany, Molecular Medicine, Hematology, recognizes cytosolic dsDNA and forms a caspase-1- activating 8. Stagi M, Gorlovoy P, Larionov S, Takahashi K, Neu- Neuroscience Institute Göttingen, University Göttingen MD, 1998 inflammasome with ASC. Nature, 458(7237), 514-518. mann H. 2006. Unloading kinesin transported cargoes 7. Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, 1995 - 2001 from the tubulin track via the inflammatory c-Jun N-terminal Speert D, Fernandes- Alnemri T, Wu J, Monks BG, Fitzgerald KA, Appointments / Positions Held Group leader, Department of Neuroimmunology, kinase pathway. FASEB J 20: 2573-5 Hornung V* and Latz E*. (2009). Cutting edge: NF-kappaB 2009 - present Full Professor of Medicine, Founder and Director of Max-Planck-Institute of Neurobiology, Martinsried activating pattern recognition and cytokine receptors license 9. Takahashi K, Rochford CD, Neumann H. 2005. the Institute of Innate Immunity, University of Bonn, Germany 1992 - 1994 NLRP3 inflammasome activation by regulating NLRP3 expression. Clearance of apoptotic neurons without inflammation by 2011- present Leader, Cooperation Unit Innate Immunity in Research fellow, Department of Neuroimmunology J Immunol, 183(2), 787-791. microglial triggering receptor expressed on myeloid cells-2. Neurodegeneration, DZNE, Bonn, Germany 8. Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock Max-Planck-Institute of Psychiatry, Martinsried J Exp Med 201: 647-57 2003 - present Assistant Professor of Medicine UMass Medical KL, Fitzgerald KA* and Latz E*. (2008). Silica crystals and 1990 - 1992 School 10. Stagi M, Dittrich PS, Frank N, Iliev AI, Schwille P, aluminum salts activate the NALP3 inflammasome through Medical Internship, Department of Neurology, University 2008 Adjunct Professor II, Institute of Cancer Research and Neumann H. 2005. Breakdown of axonal synaptic vesicle phagosomal destabilization. Nat Immunol, 9(8), 847-856. Molecular Medicine, Norwegian University of Science & Technology Ulm, Germany precursor transport by microglial nitric oxide. J Neurosci 9. Latz E, Verma A, Visintin A, Gong M, Sirois CM, Klein DC, 2007 Founder and Co-Director of UMassNanoMed, Monks BG, McKnight CJ, Lamphier MS, Duprex WP, Espevik T and 25: 352-62 UMassNanoMed Institute Honors / Awards Golenbock DT. (2007). Ligand-induced conformational changes 2003-2006 Assistant Research Professor, UMass Medical School allosterically activate Toll-like receptor 9. Nat Immunol, 8(7), 2009 - present 2001 - 2003 Postdoctoral Fellow, Division of Infectious Disease 772-779. Contribution to several patents (EP2424976B1; UMass Medical School 10. Latz E, Schoenemeyer A, Visintin A, Fitzgerald KA, Monks EP2424977B1; EP2783691A1) 2001 Postdoctoral Fellow, Evans Biomedical Research BG, Knetter CF, Lien E, Nilsen NJ, Espevik T and Golenbock DT. Center, Boston University of Medicine 2005 - 2010 (2004). TLR9 signals after translocating from the ER to CpG DNA VIce-coordinator of the EU Integrated Project Neuro- 1999 - 2001 Research Fellow, Molecular Sepsis Research Labora- in the lysosome. Nat Immunol, 5(2), 190-198. tories, Charité University Hospital, Humboldt-University of Berlin proMiSe 1998 - 2000 Internship and Residency (Intensive Care) Department * These authors contributed equally 2002 - 2009 of Surgery and Surgical Oncology, Charité University Hospital, Managing Board member of the Institute of MS Research Humboldt-University of Berlin 1998 Visiting Scientist, Department of Lipid Biochemistry, Merck Research Laboratories

192 193 Honors / Awards 2014 - 2015 Project Committee of the National e:Med Programme 2013 (Spokesman) Prof. Pierluigi Nicotera, MD PhD Prof. Markus M. Nöthen, MD 2013 - present Scientific Advisory Board of the Leipzig Research The Chancellor’s Award Lecture in Neuroscience at LSU Center for Civilization Diseases (LIFE) (Member) Neuroscience Center of Excellence, New Orleans, USA German Centre for Neurodegenerative Diseases (DZNE) Institute of Human Genetics 2013 - present Scientific Advisory Board of the Dr. Margarete 2012 Fischer-Bosch Institute of Clinical Pharmacology (IKP) and the Honorary Citizenship and Key to the City of New Orleans Robert Bosch Hospital (RBK) (Member) 2010 2012 - present International Advisory Board of iPSYCH (Lundbeck The Cardano Prize University of Pavia and Rotary Club Pavia Foundation) (Chair) 2003 2011 - present European Society of Human Genetics (Elected The Chancellor’s Award Lecture in Neuroscience at LSU Member of the Board) Neuroscience Center of Excellence, New Orleans, USA 2010 - 2012 Project Committee of the National Genome Research 2002 Network (Spokesman) “Molecular switches in neuronal cell death” Lecture at the 37th 2010 - present Scientific Advisory Board of the Medical Research Nobel Conference on Apoptosis, Stockholm Council (MRC) Centre for Neuropsychiatric Genetics and 1999 Genomics, Cardiff, UK (Member) The Jacob Hooisma Honorary Lecture at the 7th Meeting of 2010 - present German Academy of Sciences Leopoldina (National the International Neurotoxicology Association, Leicester Academy of Sciences) 1995 2009 - present Hermann Emminghausen-Prize The EUROTOX Award Lecture, 1st G. Zbinden Memorial 2008 - 2013 Project Committee of the National Genome Research Network (Elected member) Lecture Award, Prague 2007 - present Institute of Science and Ethics, Bonn (Member of 1992 the Scientific Advisory Board) German Centre for Neurodegenrative Diseases (DZNE), “Nuclear Calcium Signalling” Lecture at the 20th Nobel Rheinische Friedrich-Wilhelms-Universität Bonn National Foundation for Legasthenia and Dyscalculia (Member of Scientific Director and Chairman Conference on Calcium Signalling, Saltsjöbaden, Sweden Institute of Human Genetics, Director the Medical Advisory Board) 1992 E-Mail: [email protected] E-Mail: [email protected] 2006 - present National Alopecia Areata Foundation (Member The International Life Science Institute Research Foundation of the Medical Advisory Board) Task Force on Genetics, World U.S.A. (ILSI), award Research Expertise Federation of Societies of Biological Psychiatry Research Expertise 2005 - present International Society of Psychiatric Genetics The identification of the genetic causes of inherited diseases, and a (Elected Member of the Board) Prof. Nicotera’s main research focus is on molecular 10 Most Relevant Publications for Prof. Pierluigi special focus on genetically complex and multifactorial phenotypes. mechanisms of cell death and neurodegeneration. Nicotera 1. Michod, D., Bartesaghi, S., Khelifi, A., Bellodi, C., Ber- Education / Training 10 Most Relevant Publications for Prof. Markus M. Nöthen Education / Training liocchi, L., Nicotera P., and Salomoni, P. (2012) Calcium-De- University of Bonn, Germany, Human Genetics, Habilitation, 1996 1. Betz RC, ..., Redler S, ..., Heilmann S, …, Nöthen MM, Daly MJ, University of Pavia, Medical School, Italy, Cardiology pendent Dephosphorylation of the Histone Chaperone DAXX University of Bonn, Germany, Human Genetics, Medical Board Christiano AM (2015) Genome-wide meta-analysis in alopecia areata Regulates H3.3 Loading and Transcription upon Neuronal Qualification, 1995 Consultant, 1987 resolves HLA associations and reveals two new susceptibility loci. Nat Activation. Neuron 74(1):122-135 University of Würzburg, Germany, Internal Medicine, Commun 6:5966 Karolinska Institute, Stockholm, Biochemical Toxicology 2. Ziviani E, Lippi G, Bano D, Munarriz E, Guiducci S, Zoli M, Medical thesis, 1992, University of Würzburg, Germany, Clinical 2. Gockel I, Becker J, ..., Nöthen MM*, Boeckxstaens GE, de PhD, 1986 Young KW, Nicotera P. 2011. Ryanodine receptor-2 upregula- Medicine, MD, 1989 Bakker PI, Knapp M, Schumacher J (2014) Common variants in the University of Pavia, Medical School, Italy, Medicine MD, HLA-DQ region confer susceptibility to idiopathic achalasia. Nat Genet tion and nicotine-mediated plasticity. EMBO J 30(1): 194-204. Appointments / Positions Held 1982 3. Regad T, Bellodi C, Nicotera P, Salomoni P. 2009. The 46:901-904. doi: 10.1038/ng.3029. 2008 - present tumor suppressor Pml regulates cell fate in the developing 3. Kim S, Becker J, ..., Nöthen MM*, Müller-Myhsok B, Pütz B, Hor- Director and Chair, Institute of Human Genetics, University of Bonn, Appointments / Positions Held neocortex. Nat Neurosci 12: 132-40. nung V, Schumacher J (2014)Characterizing the genetic basis of innate Germany 4. Berliocchi L, Fava E, Leist M, Horvat V, Dinsdale D, Read immune response in TLR4-activated human monocytes. Nat Commun April 2009 - present 2006 - 2014 5:5236. doi: 10.1038/ncomms6236. D, Nicotera P. 2005. Botulinum neurotoxin C initiates two Scientific Director & Chairman of the Executive Board, Vice Dean for Research, Medical Faculty, University of Bonn, 4. Schizophrenia Working Group of the Psychiatric Genomics Con- different programs for neurite degeneration and neuronal German Centre for Neurodegenerative Diseases (DZNE), Germany sortium (2014) Biological insights from 108 schizophrenia- apoptosis. J Cell Biol 168: 607-18. Bonn, Germany 2004 - present associated genetic loci. Nature 511:421-427. doi: 10.1038/nature 5. Bano D, Young KW, Guerin CJ, Lefeuvre R, Rothwell NJ, 2002 - 2009 Alfried Krupp von Bohlen und Halbach Professor in Genetic 13595. Naldini L, Rizzuto R, Carafoli E, Nicotera P. 2005. Cleavage of Director of the British Medical Research Council Toxicology Medicine, University of Bonn, Germany 5. Ramirez A, van der Flier WM, Herold C, Ramonet D, Heilmann S, the plasma membrane Na+/Ca2+ exchanger in excitotoxicity. 2004 - present Unit and Honorary Professor of Neuroscience (Dept. of Cell ..., Nöthen MM* (2014) SUCLG2 identified as both a determinator of Cell 120: 275-85. Head, Department of Genomics, Life & Brain Center, University of CSF A 1-42 levels and an attenuator of cognitive decline in Alzhei- Physiology & Pharmacology), University of Leicester β 6. Orrenius S, Zhivotovsky B, Nicotera P. 2003. Regulation of Bonn, Germany mer’s disease. Hum Mol Genet 23:6644-6658. doi: 10.1093/hmg/ 2005 - 2008 cell death: the calcium- apoptosis link. Nat Rev Mol Cell Biol 4: 2001 - 2004 ddu372. Teaching Professor of Toxicology, Faculty of Pharmacy 552-6. Head of Department and Chair of Medical Genetics, University of 6. Mühleisen TW, Leber M, Schulze TG, Strohmaier J, Degenhardt F, University of Siena, Italy 7. Schierle GS, Hansson O, Leist M, Nicotera P, Widner H, Antwerp, Belgium …, Nöthen MM*, Cichon S (2014) Genome-wide association study 1996 - 2002 Brundin P. 1999. Caspase inhibition reduces apoptosis and 1999 - 2001 reveals two new risk loci for bipolar disorder. Nat Commun 5:3339. Foreign Adjunct Professor in Toxicology, Karolinska increases survival of nigral transplants. Nat Med 5: 97-100. Assistant Medical Director, Institute of Human Genetics 7. Cross-Disorder Group of the Psychiatric Genomics Consortium, … University of Bonn, Germany Institute, Stockholm, Sweden 8. Leist M, Single B, Castoldi AF, Kuhnle S, Nicotera P. 1997. , Nöthen MM, … , Wray N. 2013. Genetic relationship between five 1996 - 2001 1995 - 2000 Intracellular adenosine triphosphate (ATP) concentration: a psychiatric disorders estimated from genome-wide SNPs. Nat Genet Assistant Professor, Institute of Human Genetics, University of 45:984-994. C4 Professor of Molecular Toxicology, University of switch in the decision between apoptosis and necrosis. J Exp Bonn, Germany Med 185: 1481-6. 8. Ludwig KU, Mangold E, Herms S, Nowak S, Reutter H,…, Nöthen Konstanz, Germany 1991 - 1996 MM. 2012. Genome-wide meta-analyses of nonsyndromic cleft lip 9. Bonfoco E, Krainc D, Ankarcrona M, Nicotera P, Lip- 1989 - 1994 Postdoctoral Fellow, Institute of Human Genetics, University of with or without cleft palate identify six new risk loci. Nat Genet 44:968- Senior University Lecturer, Karolinska Institute, Stockholm, ton SA. 1995. Apoptosis and necrosis: two distinct events Bonn, Germany 971. Sweden induced, respectively, by mild and intense insults with 1990 - 1991 9. Cichon S, Mühleisen TW, Degenhardt FA, Mattheisen M,..., 1992 N-methyl-D- aspartate or nitric oxide/superoxide in cortical cell Internship, Institute of Human Genetics, University of Bonn, Schumacher J, Maier W, Propping P, Rietschel M, Nöthen MM*. cultures. Proc Natl Acad Sci U S A 92: 7162-6. Docent in Molecular Toxicology, Karolinska Institute, Germany 2011. Genome-wide association study identifies genetic variation 10. Ankarcrona M, Dypbukt JM, Bonfoco E, Zhivotovsky in neurocan as a susceptibility actor for bipolar disorder. Am J Hum Stockholm, Sweden Honors / Awards B, Orrenius S, Lipton SA, Nicotera P. 1995. Glutamate-in- Genet 88:372-381. 1986 - 1989 duced neuronal death: a succession of necrosis or apoptosis 2016 - present National Genetic Diagnostic Commission (Perma- 10. Birnbaum S, Ludwig KU,..., Nöthen MM, Mangold E*. 2009. Key Research assistant Professor, Department of Karolinska depending on mitochondrial function. Neuron 15: 961-73. nent Guest on behalf of the German Medical Association) susceptibility locus for nonsyndromic cleft lip with or without cleft palate Institute, Stockholm, Toxicology, Sweden 2015 - present Life & Brain GmbH, Bonn (Scientific Director) on chromosome 8q24. Nat Genet 41: 473-477. 2015 - present Project Committee of the National e:Med Pro- gramme (Elected Member) * Publications with more than 10 authors have been shortened

194 195 2006 10 Most Relevant Publications for Prof. Michael Prof. Natalija Novak, MD Heisenberg-Fellowship, German Research Council Prof. Michael J. Pankratz, PhD Pankratz Travel Award EAACI Vienna, Austria 1. Hückesfeld S, Schoofs A, Schlegel P, Miroschnikow A, 2005 Department of Dermatology and Allergy Life and Medical Sciences Institute (LIMES) Pankratz MJ. Localization of Motor Neurons and Central Heinz Maier-Leibnitz Award, German Research Council Pattern Generators for Motor Patterns Underlying Feed- Research Award Atopische Dermatitis, Dermatologikum Hamburg ing Behavior in Drosophila Larvae. PLoS One 2015 Aug Young Investigator Travel Award, ISAD Meeting Acachand 7;10(8):e0135011. 2004 2. Alekseyenko OV, Chan YB, Fernandez Mde L, Bülow T, Karl-Hansen Memorial Award, German Society for Allergology Pankratz MJ, Kravitz EA. Single serotonergic neurons that and Immunology (DGAKI) modulate aggression in Drosophila. Curr Biol 2014 Nov 2003 17;24(22):2700-7. Fujisawa “Young Investigator Achievements Award in Atopic 3. Schoofs A, Hückesfeld S, Schlegel P, Miroschnikow A, Dermatitis Research” Peters M, Zeymer M, Spieß R, Chiang AS, Pankratz MJ. Award, Herbert-Reeck-Society 2014. Selection of motor programs for suppressing food in- Honourable Mention Diploma Pharmacia Research Foundation take and inducing locomotion in the Drosophila brain. PLoS Travel Award EAACI Meeting, Davos, Switzerland Biol, in press. Erich-Hoffmann Memorial Award 4. Bader R, Sarraf-Zadeh L, Peters M, Moderau N, Stock- 2002 er H, Köhler K, Pankratz MJ*, Hafen E. 2013. The IGFBP7 Herbert-Herxheimer Award, German Society for Allergology homolog Imp-L2 promotes insulin signaling in distinct and Immunology (DGAKI) neurons of the Drosophila brain. J Cell Science 126, 2571- 2002 Rheinische Friedrich-Wilhelms-Universität Bonn Rheinische Friedrich-Wilhelms-Universität Bonn 2576. BONFOR Award Department of Dermatology and Allergy Life and Medical Sciences Institute (LIMES), 5. Bülow M, Aebersold R, Pankratz MJ*, Jünger M. Department of Molecular Brain Physiology and 2010. The Drosophila FoxA Ortholog Fork Head Regulates E-Mail: [email protected] 10 Most Relevant Publications for Prof. Natalija Novak Behavior, Director Growth and Gene Expression Downstream of Target of 1. Yu CF, Peng WM, Oldenburg J, Hoch J, Bieber T, Limmer Research Expertise E-Mail: [email protected] Rapamycin. PLoS One 5(12): e15171. A, Hartmann G, Barchet W, Eis-Hubinger AM, Novak N. 2010. 6. Min KJ, Yamamoto R, Buch S, Pankratz MJ, Tatar Human plasmacytoid dendritic cells support Th17 cell effector Pathophysiology of atopic dermatitis including genetic M. 2008. Drosophila lifespan control by dietary restriction function in response to TLR7 ligation. J Immunol 184: 1159-67. Research Expertise changes, regulation of the surface expression of the high independent of insulin-like signaling. Aging Cell 7: 199-206. affinity receptor for IgE on dendritic cells, role of IgE recep- 2. Allam JP, Würtzen PA, Reinartz M, Winter J, Vrtala S, Chen KW, Prof. Pankratz is an expert on the genetics of nutrient Valenta R, Wenghoefer M, Appel T, Gros E, Niederhagen B, Bieber 7. Buch S, Melcher C, Bauer M, Katzenberger J, Pankratz tor bearing Langerhans cells and inflammatory dendritic control, feeding behavior, gustation and neuroendocrine T, Lund K, Novak N. 2010. Phl p 3 resorption in human oral muco- MJ. 2008. Opposing effects of dietary protein and sugar epidermal cells, predictive factors for atopy in cord-blood, sa leads to dose-dependent and time-dependent allergen binding circuits in drosophila. regulate a transcriptional target of Drosophila insulin-like development and characterization of new therapeutic strat- by oral mucosal Langerhans cells, attenuates their maturation, and peptide signaling. Cell Metab 7: 321-32. egies for atopic dermatitis, role of dendritic cells in the oral enhances their migratory and TGF-β1 and IL-10 producing proper- Education / Training 8. Melcher C, Bader R, Pankratz MJ. 2007. Amino acids, and nasal mucosa. ties. J Allergy Clin Immunol 126: 638-45. University of California, Los Angeles USA, Biochemistry taste circuits, and feeding behavior in Drosophila: towards 3. Gros E, Bussmann C, Bieber T, Forster I, Novak N. 2009. PhD, 1986 understanding the psychology of feeding in flies and man. J Education / Training Expression of chemokines and chemokine receptors in lesional and nonlesional upper skin of patients with atopic dermatitis. J Allergy Johns Hopkins University, USA, Biology BA, 1980 Endocrinol 192: 467-72. University of Bonn, Germany, Medicine, MD., 1998 Clin Immunol 124: 753-60 e1. 9. Bader R, Colomb J, Pankratz B, Schrock A, Stocker 4. Esparza-Gordillo J, Weidinger S, Folster-Holst R, Bauerfeind Appointments / Positions Held RF, Pankratz MJ. 2007. Genetic dissection of neural circuit Appointments / Positions Held A, Ruschendorf F, Patone G, Rohde K, Marenholz I, Schulz F, 2008 - present anatomy underlying feeding behavior in Drosophila: distinct 2008 - present Kerscher T, Hubner N, Wahn U, Schreiber S, Franke A, Vogler R, Full Professorship, Molecular Brain Physiology, University of classes of hugin-expressing neurons. J Comp Neurol 502: Heath S, Baurecht H, Novak N, Rodriguez E, Illig T, Lee-Kirsch Full Professor of Dermatology and Allergy, University of Bonn 848-56. MA, Ciechanowicz A, Kurek M, Piskackova T, Macek M, Lee YA, 10. Melcher C, Bader R, Walther S, Simakov O, Pankratz Bonn, Germany Ruether A. 2009. A common variant on chromosome 11q13 is 2001 - 2007 MJ. 2006. Neuromedin U and its putative Drosophila ho- 2009 associated with atopic dermatitis. Nat Genet 41: 596-601. Senior Group Leader, Genetics, Karlsruhe, Institute of Board, Andrology, University of Bonn, Germany 5. Kwiek B, Peng WM, Allam JP, Langner A, Bieber T, Novak N. Technology molog hugin. PLoS Biol 4: e68. 2006 - 2007 2008. Tacrolimus and TGF-beta act synergistically on the genera- 2001 Visiting scientist, Heisenberg-Fellowship, Swiss Institute of tion of Langerhans cells. J Allergy Clin Immunol 122: 126-32, 32 Habilitation, Genetics, Karlsruhe University * Corresponding author Allergy and Asthma Research, Davos, Switzerland e1. 1997 - 2001 2004 6. Weidinger S, Illig T, Baurecht H, Irvine AD, Rodriguez E, Group Leader, Institute of Genetics, Karlsruhe, Institute of Diaz-Lacava A, Klopp N, Wagenpfeil S, Zhao Y, Liao H, Lee SP, Board, Allergy, University of Bonn, Germany Palmer CN, Jenneck C, Maintz L, Hagemann T, Behrendt H, Ring Technology 2003 J, Nothen MM, McLean WH, Novak N. 2006. Loss-of-function 1993 - 1997 Assistant Professor, Dermatology and Allergy, University of variations within the filaggrin gene predispose for atopic dermatitis Staff Scientist, Institute of Biophysical Chemistry, Max Bonn, Germany with allergic sensitizations. J Allergy Clin Immunol 118: 214-9. Planck Institute Assistant to Medical Director, Dermatology, University of 7. Novak N, Valenta R, Bohle B, Laffer S, Haberstok J, Kraft S, 1988 - 1992 Bonn, Germany Bieber T. 2004. FcepsilonRI engagement of Langerhans cell- Postdoctoral Fellow, Institute for Genetics and Microbiology, Board, Dermatology, University of Bonn, Germany like dendritic cells and inflammatory dendritic epidermal cell-like University of Munich dendritic cells induces chemotactic signals and different T-cell 1987 - 1988 phenotypes in vitro. J Allergy Clin Immunol 113: 949-57. Honors / Awards 8. Novak N, Allam JP, Hagemann T, Jenneck C, Laffer S, Valenta Postdoctoral Fellow, Institute for Developmental Biology 2014 R, Kochan J, Bieber T. 2004. Characterization of FcepsilonRI-bear- Max Planck Institute Allergopharma Award ing CD123 blood dendritic cell antigen-2 plasmacytoid dendritic 2012 cells in atopic dermatitis. J Allergy Clin Immunol 114: 364-70. Honors / Awards Henning-Löwenstein Award World Allergy Organization 9. Novak N, Tepel C, Koch S, Brix K, Bieber T, Kraft S. 2003. Evi- 2003 - 2005 2008 dence for a differential expression of the FcepsilonRIgamma chain in dendritic cells of atopic and nonatopic donors. J Clin Invest 111: Member of the Scientific Advisory Board “Network Phadia International Award on Allergy Research, Phadia of Molecular Nutrition Research“, State of Baden- 2007 1047-56. 10. Novak N, Bieber T, Katoh N. 2001. Engagement of Fc epsilon Württemberg, Germany Heisenberg-Professorship, German Research Council RI on human monocytes induces the production of IL-10 and pre- 2000 - 2001

vents their differentiation in dendritic cells. J Immunol 167: 797-804 Consultant for Aventis

196 197 America Honors / Awards 1997 Travel Award Annual Meeting of the American Society of 2015 Prof. Joachim L. Schultze, MD Hematology Prof. Thomas Tüting, MD 1997 Leukemia Clinical Research Award (Deutsche Gesellschaft Photodermatology Research Award (Roche Posay) Life and Medical Sciences Institute (LIMES) für Hämatologie und Onkologie) Department of Dermatology and Allergy 2014 Arnold Rikli prize of the Jörg Wolff Stiftung 10 Most Relevant Publications for Prof. Joachim L. 2014 Schultze German skin cancer research prize of the German skin 1. Beyer M, Abdullah Z, Chemnitz JM, Maisel D, Sander J, cancer foundation Lehmann C, Thabet Y, Shinde PV, Schmidleithner L, Köhne M, 2009 Trebicka J, Schierwagen R, Hofmann A, Popov A, Lang KS, Steigleder prize of the AG Dermatological Histology Oxenius A, Buch T, Kurts C, Heikenwälder M, Fätkenheuer G, 2006 Lang PA, Hartmann P, Knolle PA, Schultze JL. TNF impairs Translational Research prize of the AG Dermatological CD4+ T-cell mediated immune control in chronic viral infection. Research Nat Immunol. 2016 Mar 7. [Epub ahead of print] 2000 2. Schmidt SV, Krebs W, Ulas T, Xue J, Baßler K, Günther P, Hardt A-L, Schultze H, Sander J, Klee K, Theis H, Kraut M, Research Award of the Erich Hoffmann Society, Bonn Beyer M, Schultze JL. The transcriptional regulator network of human inflammatory macrophages is defined by open chroma- 10 Most Relevant Publications for Prof. Thomas Tüting tin. Cell Res. 2016 Jan 5. 1. Baar M, Coquille L, Mayer H, Hölzel M, Rogava M, Tüting 3. Ginhoux F, Schultze JL, Murray PJ, Ochando J, Biswas SK. T, Bovier A. A stochastic model for immunotherapy of cancer. New insights into the multidimensional concept of macrophage Sci Rep 6:24169, 2016. Rheinische Friedrich-Wilhelms-Universität Bonn ontogeny, activation and function. Nat Immunol. 2015 Dec Rheinische Friedrich-Wilhelms-Universität Bonn 2. Hölzel M, Landsberg J, Glodde N, Bald T, Rogava M, Life and Medical Sciences Institute (LIMES), 17;17(1):34-40. All authors contributed equally Department of Dermatology and Allergy Riesenberg S, Becker AJ, Jonsson G, Tüting T. A preclinical 4. . Teaching ‘big data’ analysis to young immunol- model of malignant peripheral nerve sheath tumor-like mela- Genomics & Immunoregulation, Director Schultze JL E-Mail: [email protected] ogists. Nat Immunol. 2015 Aug 19;16(9):902-5. noma is characterized by infiltrating mast cells. Cancer Res E-Mail: [email protected] 5. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Go- 76:251-63, 2015. Research Expertise Research Expertise erdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, Locati 3. Riesenberg S, Groetchen A, Siddaway R, Bald T, Rein- hardt J, Smorra D, Kohlmeyer J, Renn M, Phung B, Aymans Professor Schultze’s current central expertise is at the inter- M, Mantovani A, Martinez FO, Mege JL, Mosser DM, Natoli G, Role of UV irradiation and the immune system in the P, Schmidt T, Hornung V, Davidson I, Goding CR, Jönsson G, phase of immunoregulation and genomics, with a focus on Saeij JP, Schultze JL, Shirey KA, Sica A, Suttles J, Udalova I, pathogenesis of melanoma; mechanisms of melanoma Landsberg J, Tüting T, Hölzel M. MITF and c-Jun antagonism transcriptional and epigenetic control of cell activation and im- van Ginderachter JA, Vogel SN, Wynn TA. Macrophage activa- metastasis and therapy resistance; preclinical and clinical tion and polarization: nomenclature and experimental guide- interconnects melanoma dedifferentiation with pro-inflamma- munoregulation, particularly in macrophages and monocytes. evaluation of approaches combining immunotherapies and lines. Immunity. 2014; 41(1):14-20 authors in alphabetical order other treatment modalities for melanoma; development of tory cytokine responsiveness and myeloid cell recruitment. Nat Commun 6:8755, 2015. Education / Training except for P. Murray novel genetic mouse models to study inflammation-induced 4. Bald T, Landsberg J, Lopez-Ramos D, Renn M, Glodde University of Freiburg, Medicine Fellow, 1992 - 1993 6. Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W, Quester phenotypic plasticity and reciprocal interactions between N, Jansen P, Gaffal E, Steitz J, Tolba R, Kalinke U, Limmer A, University of Tübingen, Medicine, MD, 1991 I, De Nardo D, Gohel TD, Emde M, Schmidleithner L, Ganesan melanoma, immune and endothelial cells in the perivascular Jönsson G, Hölzel M, Tüting T. Immune-cell poor melanomas University of Tübingen, Medicine, State examination, 1991 H, Nino-Castro A, Mallmann MR, Labzin L, Theis H, Kraut M, niche. Beyer M, Latz E, Freeman TC, Ulas T, Schultze JL. Transcrip- benefit from PD-1 blockade after targeted type I IFN activation. Appointments / Positions Held tome-based network analysis reveals a spectrum model of Cancer Discovery 4:674-87, 2014. Education / Training 5. Bald T, Quast T, Landsberg J, Rogava M, Glodde N, 2007 - present W3 Professorship, Genomics & Immunoregula- human macrophage activation. Immunity. 2014; 40(2):274-88 Lopez-Ramos D, Kohlmeyer J , Riesenberg,S. van den tion, University of Bonn 7. De Nardo D, Labzin LI, Kono H, Seki R, Schmidt SV, Beyer University of Frankfurt, Germany, MD, Thesis, 2000 Boorn-Konijnenberg D, Hömig-Hölzel C, Reuten R, Schadow 2002 - 2007 C3 Professorship, Tumor Immunology, University M, Xu D, Zimmer S, Lahrmann C, Schildberg FA, Vogelhuber University of Mainz, Germany, Dermatology and Allergic B, Weighardt I, Wenzel D, Helfrich I, Schadendorf D, Bloch of Cologne J, Kraut M, Ulas T, Kerksiek A, Krebs W, Bode N, Grebe A, Diseases, Board Certification, 1998 W, Bianchi ME, Koch M, Fleischmann BK, Förster I, Kasten- 1997 - 2002 Instructor in Medicine, Adult Oncology, Daner-Far- Fitzgerald ML, Hernandez NJ, Williams BR, Knolle P, Kneilling University of Frankfurt School of Medicine, Medicine, MD, müller W, Kolanus W, Hölzel M, Gaffal E, Tüting T. Ultraviolet ber Cancer Institute, MA, USA M, Röcken M, Lütjohann D, Wright SD, Schultze JL*, Latz E*. 1987 radiation-induced inflammation promotes angiotropism and 1996 - 1997 Instructor in Medicine, Hematologic Malignancies, High-density lipoprotein mediates anti-inflammatory reprogram- metastasis in melanoma. Nature 507:109-13, 2014. Daner-Farber Cancer Institute, MA, USA ming of macrophages via the transcriptional regulator ATF3. Nat Appointments / Positions Held 6. Hölzel M, Bovier A, Tüting T. Plasticity of tumour and im- 1995 - 1996 Research Associate, Hematology, Daner-Farber Immunol. 2014; 15(2):152-60 *Shared last author 2015 - present Professor and Chairman, Department of mune cells: a source of heterogeneity and a cause for therapy Cancer Institute, MA, USA 8. Beyer M, Thabet Y, Müller RU, Sadlon T, Classen S, Lahl Dermatology, University of Magdeburg, Germany resistance? Nat Rev Cancer. 13:365-76, 2013. 1993 - 1995 Research Fellow, Hematology, Daner-Farber K, Basu S, Zhou X, Bailey-Bucktrout SL, Krebs W, Schönfeld 2001 - present 7. Gaffal E, Cron M, Glodde N, Bald T, Kuner R, Zimmer A, Cancer Institute, MA, USA EA, Böttcher J, Golovina T, Mayer CT, Hofmann A, Sommer D, Debey-Pascher S, Endl E, Limmer A, Hippen KL, Blazar BR, Associate Professor and Laboratory Head, Experimental Lutz B, Tüting T. Cannabinoid 1 receptors in keratinocytes Honors / Awards Balderas R, Quast T, Waha A, Mayer G, Famulok M, Knolle PA, Dermatology, University of Bonn, Germany modulate proinflammatory chemokine secretion and attenuate 2015 - present Founding Director of the Platform for Genomics and Wickenhauser C, Kolanus W, Schermer B, Bluestone JA, Barry 2001 - present contact allergic inflammation. J. Immunol. 190:4929-36, 2013. Epigenomics at the University of Bonn and the DZNE SC, Sparwasser T, Riley JL, Schultze JL. Repression of the Clinical work, General and Oncologic Dermatology, 8. Gehrke N, Mertens C, Zillinger T, Wenzel J, Bald T, Zahn S, 2012 - present Vice Dean for Research, Faculty for Mathematics genome organizer SATB1 in regulatory T cells is required for University of Bonn, Germany Tüting T, Hartmann G, Barchet W. Oxidative damage of DNA and Natural Sciences, University of Bonn suppressive function and inhibition of effector differentiation. Nat 1998 - 2001 confers resistance to cytosolic nuclease TREX1 degradation 2010 Patent: A method for lung cancer early detection and Immunol. 2011; 12(9):898-907 Clinical and Scientific Work, Department of Dermatology, and potentiates STING-dependent immune sensing. Immunity. 39:482-95, 2013. prognosis. Zander T, Schultze JL, Wolf J, Staratschek-Jox A, 9. Becker T, Loch G, Beyer M, Zinke I, Aschenbrenner AC, University of Mainz, Germany Debey-Pascher S, Eggle D, Boffetta P, Linseisen J. 9. Landsberg J, Kohlmeyer J, Renn M, Bald T, Rogava M, Carrera P, Inhester T, Schultze JL, Hoch M. FOXO-depen- 1995 - 1997 2009 Patent: Anticancer Agent. Hoch M, Schultze JL, Loer B. dent regulation of innate immune homeostasis. Nature. 2010; Cron M, Fatho M, Lennerz V, Wölfel T, Hölzel H, Tüting T. 2009 Patent: Novel Marker Genes for regulatory T cells from hu- Research Fellow in Tumor Immunology and Gene Therapy, Melanomas resist T-cell therapy through inflammation-induced 463(7279):369-73 Department of Surgery, University of Pittsburgh School of man blood. Schultze JL, Beyer MD, Warner N, Hingorani R. 10. Trojan A*, Schultze JL*, Witzens M, Vonderheide RH, Ladet- reversible dedifferentiation. Nature. 490:412-416, 2012. Medicine, Pittsburgh, PA 2002 Sofja-Kovalevskaja Award of the Alexander von to M, Donovan JW, Gribben JG. Immunoglobulin framework-de- 10. Kohlmeyer J, Cron M, Landsberg J, Bald T, Renn M, Mikus Humboldt-Foundation 1991 - 1995 rived peptides function as cytotoxic T-cell epitopes commonly S, Bondong S, Wikasari D, Gaffal E, Hartmann G, Tüting T. 2000 Senior Investigator Award of the Multiple Myeloma Research expressed in B-cell malignancies. Nat Med. 2000; 6(6):667-72 Residency in Dermatology and Allergic Diseases, Complete regression of advanced primary and metastatic Foundation Department of Dermatology, Military Hospital Koblenz and mouse melanomas following combination chemoimmunother- 1999 Translational Research Award of the Leukemia & Lymphoma *Shared first author University of Mainz, Germany apy. Cancer Res 69:6265-74, 2009. Society 1988 - 1991 1998 Special Fellowship Award of the Leukemia & Lymphoma Society Drafted as Airforce Medical Officer, Fighter- Bomber Wing 1997 Fellowship Award of the Lymphoma Research Foundation of 33, Cochem, Germany * These authors contributed equally

198 199 Honors / Awards Prof. Andreas Zimmer, PhD 2000 U.S. Department of Health and Human Services Special Institute of Molecular Psychiatry Act or Service Award 1990 - 1992 DFG-Fellow 1987 - 1989 Max-Planck-Fellow 1989 PhD thesis awarded ‘summa cum laude’

10 Most Relevant Publications for Prof. Andreas Zimmer 1. Miró X, Meier S, Dreisow ML, Frank J, Strohmaier J, Breuer R, Schmäl C, Albayram O, Pardo-Olmedilla MT, Mühleisen TW, Degenhardt FA, Mattheisen M, Reinhard I, Bilkei-Gorzo A, Cichon S, Seidenbecher C, Rietschel M, Nöthen MM, Zimmer A. (2012). Studies in humans and mice implicate neurocan in the etiology of mania. Am J Psychiatry,169(9):982-90. 2. Gertsch J, Leonti M, Raduner S, Racz I, Chen JZ, Xie Rheinische Friedrich-Wilhelms-Universität Bonn XQ, Altmann KH, Karsak M, Zimmer A. 2008. Beta-caryo- Institute of Molecular Psychiatry, Director phyllene is a dietary cannabinoid. Proc Natl Acad Sci U S A E-Mail: [email protected] 105: 9099-104. 3. Karsak M, Gaffal E, Date R, Wang-Eckhardt L, Rehnelt Research Expertise J, Petrosino S, Starowicz K, Steuder R, Schlicker E, Cra- Prof. Zimmer and his groups are interested in the molecular vatt B, Mechoulam R, Buettner R, Werner S, Di Marzo V, mechanisms of neuropsychiatric disorders with a focus on Tuting T*, Zimmer A*. 2007. Attenuation of allergic contact addiction, pain and affective disorders, molecular biology of dermatitis through the endocannabinoid system. Science modulatory neurotransmitters, and the molecular biology of 316: 1494-7. aging. 4. Bilkei-Gorzo A, Racz I, Valverde O, Otto M, Michel K, Sastre M, Zimmer A. 2005. Early age-related cognitive Education / Training impairment in mice lacking cannabinoid CB1 receptors. Proc Natl Acad Sci U S A 102: 15670-5. Max Planck Institute for Biophysical Chemistry, 5. Nadeau JH, Balling R, Barsh G, Beier D, Brown SD, Microbiology, PhD, 1989 Bucan M, Camper S, Carlson G, Copeland N, Eppig J, Justus-Liebig Universität Giessen, Biology, Fletcher C, Frankel WN, Ganten D, Goldowitz D, Good- Diploma, 1986 now C, Guenet JL, Hicks G, Hrabe de Angelis M, Jackson I, Jacob HJ, Jenkins N, Johnson D, Justice M, Kay S, Appointments / Positions Held Kingsley D, Lehrach H, Magnuson T, Meisler M, Poustka A, 2006 - present Rinchik EM, Rossant J, Russell LB, Schimenti J, Shiroishi T, Professor of Molecular Psychiatry (W3), Director, Institute Skarnes WC, Soriano P, Stanford W, Takahashi JS, Wurst for Molecular Psychiatry, University of Bonn W, Zimmer A. 2001. Sequence interpretation. Functional 2005 - 2006 annotation of mouse genome sequences. Science 291: Professor of Cell Biology (W3), University of Bielefeld 1251-5. 1999 - 2005 6. Zimmer A, Zimmer AM, Hohmann AG, Herkenham Professor for Molecular Neurobiology (C3), University of M, Bonner TI. 1999. Increased mortality, hypoactivity, and Bonn hypoalgesia in cannabinoid CB1 receptor knockout mice. 1997 - 1999 Proc Natl Acad Sci U S A 96: 5780-5. Adjunct Professor, Department of Pharmacology, 7. Hahn H, Wojnowski L, Zimmer AM, Hall J, Miller G, Georgetown University, Medical School, USA Zimmer A. 1998. Rhabdomyosarcomas and radiation Main Building University of Bonn at night 1997 - 2000 hypersensitivity in a mouse model of Gorlin syndrome. Nat by Frank Luerweg Research Fellow, National Institute of Mental Health, USA Med 4: 619-22. 1995 - 1997 8. Wojnowski L, Zimmer AM, Beck TW, Hahn H, Bernal R, Visiting Research Fellow, National Institute of Mental Health, Rapp UR, Zimmer A. 1997. Endothelial apoptosis in Braf- USA deficient mice. Nat Genet 16: 293-7. 1991 - 1995 9. Konig M, Zimmer AM, Steiner H, Holmes PV, Crawley Visiting Associate, National Institute of Mental Health, USA JN, Brownstein MJ, Zimmer A. 1996. Pain responses, 1991 - 2000 anxiety and aggression in mice deficient in pre-proenkeph- Section Head, National Institute of Mental Health, USA alin. Nature 383: 535-8. 1989 - 1991 10. Zimmer A, Gruss P. 1989. Production of chimaeric Postdoctoral researcher, DFG-Fellow, National Institute of mice containing embryonic stem (ES) cells carrying a ho- Mental Health, USA moeobox Hox 1.1 allele mutated by homologous recombination. Nature 338: 150-3.

*These authors contributed equally

200 201 INTERNATIONAL SCIENTIFIC Organigram ADVISORY BOARD Anthony Cerami Steve Cohen Charles Dinarello Douglas T. Golenbock Herbert Jäckle Luke O‘Neill Hidde Ploegh Brigitta Stockinger Hermann Wagner GENERAL ASSEMBLY Tony Wyss-Coray

RECTORATE CLUSTER COORDINATION OFFICE Gunther Hartmann Speaker Cluster Management: Catherine Drescher Central Administration/ Waldemar Kolanus FACULTIES Family Support: Nicole Dahms Vice Speaker IITB Coordination: Catherine Drescher Eva Bartok RECRUITMENT COMMITTEE Public Relations: Elisabeth Mettke Financial Administrator: Ida Bartz IT & Data Management/ Ofﬁce of Shared Resources: Andriy Kubarenko Maternity Leave Cornelia Hömig-Hölzel

STEERING COMMITTEE

EXECUTIVE BOARD SUBCOMMITTEES Irmgard Förster Michael Heneka * Gender Equality Annett Halle Michael Hoch * Promotion of Young Researchers (IITB) Gunther Hartmann Achim Hörauf U. Benjamin Kaupp Veit Hornung Waldemar Kolanus Percy Knolle Christian Kurts Markus M. Nöthen Eicke Latz Michael Pankratz Pierluigi Nicotera Joachim L. Schultze Andreas Zimmer

RESEARCH AREA A B C D E

Immune Sensing Local Context Sensing Metabolic Sensing and Integration of Immune Consequences of Receptors and Nervous-Immune Sensory System Input Immune Sensing for Modulators System Interactions on the Cellular and Sterile Inﬂammation Subcellular Level in Vivo

203 Participating Participating Institutions & CCO Institutions

Medical Faculty LIMES - Life & Medical Sciences Institute University of Bonn University of Bonn Sigmund-Freud-Straße 25 Carl-Troll-Straße 31 D-53127 Bonn D-53115 Bonn www.ukb.uni-bonn.de www.limes-institut-bonn.de

DZNE - German Centre for caesar - center of advanced european Neurodegenerative Diseases studies and research Ludwig-Erhard-Allee 2 Ludwig-Erhard-Allee 2 D-53175 Bonn D-53175 Bonn www.dzne.de www.caesar.de

Cluster Coordination Office University Hospital Bonn BMZI / UG / 216.3 Sigmund-Freud-Straße 25 D-53127 Bonn Phone: +49 (0)228 287 51288 Fax: +49 (0)228 287 51388 Email: [email protected] www.immunosensation.de

205 Cluster Coordination Office (CCO) Cluster Coordination 2016

Dr. Catherine Drescher Nicole Dahms Dr. Elisabeth Mettke Office (CCO) Cluster Manager Central Administration & Family Public Relations Phone +49 228 287 51286 Support Phone +49 228 287 51283 [email protected] Phone +49 228 287 51288 [email protected] [email protected]

ImmunoSensation Cluster of Excellence University of Bonn University Hospital Bonn

Sigmund-Freud-Str. 25 D-53127 Bonn

www.immunosensation.de

Dr. Andriy Kubarenko Ida Bartz Dr. Cornelia Hömig-Hölzel IT and Data Management Financial Administrator Maternity Leave Phone +49 228 287 51290 [email protected] [email protected]

Eva Bartok, MD IITB support

207 Appendix: Shared Shared Resources Initiative

The Office of Shared Resources (OSR) the services available and how to access has been part of the Cluster Coordina- them. In 2015, the OSR implemented a Resources tion Office since 2014. The OSR acts as regular Core Facility meeting with plat- a central access point for resources that form and facility managers, where ideas, are shared on a scientific basis (collabora- problems and technical questions are dis- tion), on a financial basis (usage of instru- cussed to further improve user services. ments and equipment) or within Core Fa- All Core Facilities and platforms (Figure Flow Cytometry Core Facility cilities/ platforms. The OSR also provides 1) are willing to share their expertise and Imaging Core Facility a “Handbook of Shared Resources”, instrumentation with Cluster members. which provides users with an overview of Transgenic Core Facility Mass Spectrometry Core Facility Live Cell Imaging Platform Shared Resources Core Unit Flow Cytometry Core Facility Next Generation Sequencing Core Facility Institute of Clinical Chemistry and Institute of Molecular Medicine Genomics Platform Clinical Pharmacology, Faculty of Medicine Faculty of Medicine Director: Prof. Gunther Hartmann Director: Prof. Veit Hornung Contact: Dr. Andriy Kubarenko Contact: Dr. Elmar Endl [email protected] [email protected] 0228/287-51290 0228/287-11028

Imaging Core Facility Transgenic Core Facility Institute of Innate Immunity Haus für Experimentelle Therapie Faculty of Medicine (HET), Faculty of Medicine Director: Prof. Eicke Latz Director: Dr. Wolfgang Eichelkraut Contact: Dr. Gabor Horvath Contact: Dr. David-Marian Otte [email protected] [email protected] 0228/287-51229 0228/287-11652

Mass Spectrometry Core Facility Live Cell Imaging Platform Institute of Biochemistry & Molecular Molecular Immunology and Cell Biology, Faculty of Medicine Biology Director: Prof. Volkmar Gieselmann LIMES Institute Director: Prof. Waldemar Kolanus Contact: Dr. Marc Sylvester [email protected] Contact: Dr. Thomas Quast 0228/73-4744 [email protected] 0228/73-62781 Next Generation Sequencing Core Facility Genomics Platform Institute of Human Genetics Genomics and Immunoregulation Faculty of Medicine LIMES Institute Director: Prof. Markus Nöthen Director: Prof. Joachim L. Schultze Contact: Dr. rer. nat. Kerstin Ludwig Contact: Dr. Kathrin Klee [email protected] [email protected] 0228/6885420 0228/73-62777

Figure 1 Shared Resources Initiative Team (December 2015).

209 Imprint Imprint

Editor ImmunoSensation Cluster of Excellence Sigmund-Freud-Str. 25 53127 Bonn

Edited by Eva Bartok, MD Nicole Dahms Dr. Catherine Drescher Prof. Gunther Hartmann Dr. Elisabeth Mettke

Text Layout Dr. Elisabeth Mettke

Cover The cover image shows the graphical summary of ‘Sequence-specific activation of the DNA sensor cGAS by Y-form DNA structures as found in primary HIV-1 cDNA’ on page 17.

Graphic Design Andreas Müller-Gaida MOWMAN DESIGNBUERO Buchholzstr. 44 51061 Cologne Germany

Photography p.9, p. 165-200, p. 207 Johann F. Saba/ UKB; p. 205 DZNE building by wulf ar- chitekten GmbH; p. 55, 63, p. 68-71, p. 82, p. 100-101 Jörg Heupel, Bonn; p.91 Volker Lannert

Print Unternehmenskommunikation Universitätsklinikum Bonn

Druckerei Eberwein Auf dem Kummgraben 10 53343 Wachtberg-Villip

211 www.immunosensation.de