C.V. Rainer HUBMANN, Phd, PI

C.V. Rainer HUBMANN, PhD, PI Medical University of Vienna Comprehensive Cancer Center Department of Medicine I Währinger Gürtel 18-20, Vienna, A-1090 Phone: +43-1-40 400-52830 e-mail: [email protected]

PERSONAL DETAILS

Title & Name: Mag. Dr. Rainer HUBMANN Date and Place of Birth: 1st March 1968, Vienna, Austria Citizenship: Austria Permanent address: Kirchengasse 12A/13 A-2273 Hohenau an der March

EDUCATION

1974-1978 Primary School, Vienna 1978-1986 High School, Vienna 1987-1996 Biology/Genetic (Master degree) (University of Vienna, VBC/MFPL; Group H. Hirth) Member of the Cell Cycle Club (IMP, Leader: Kim Nasmyth) 1997-2002 Ph.D. Thesis: Regulation of CD23 in CLL (MUW/LBI for Cytokine Research; Leader: JD. Schwarzmeier) 2002-2008 Postdoc: Regulation and function of NOTCH2 in CLL (MUW/LBI for Cytokine Research; Leader: JD. Schwarzmeier) 2008-2011 Postdoc: Identification & characterization of CLL stem cells (Ludwig Boltzmann Cluster Oncology, Leader: P. Valent) 2011-2015 Principal Investigator (PI): Targeting NOTCH2 signaling in CLL, HCC, melanoma, & pancreas-CA (MUW/CCC/DTSU; Leader: M. Shehata)

RESEARCH/INNOVATION

 Identification of the first D-type Cyclin in higher plants.  Dissecting the pathomechanism of CLL by reverse genetics (from phenotype to genotype).  Elucidating the regulation & function of NOTCH receptors in B-cell development, CLL leukemogenesis, and in solid tumors.  Identification of NOTCH2 as most frequent mutated oncogene in CLL  Identification of GLIOTOXIN as therapeutic relevant NOTCH2 transactivation inhibitor for CLL and for NOTCH2 associated solid tumors like HCC, melanoma, & pancreas-CA.

PATENTS

 WO/2006/135949; US Patent No 7,981,878: Gliotoxin for the treatment of NOTCH2 associated malignancies.

1 TECHNICAL SKILLS

Gain and loss of function analysis (Retroviral expression vectors, siRNA KO experiments in CLL cells); RT-PCR; Northern & Western blotting, EMSA, RACE; Genomic analysis & gene mutation/deletion screening; Bioinformatics (Sequence analysis); in vitro expression kinetic studies; translating basic research into clinical practice; drug screening models; xenograft mouse models, PI in the DTSU drug development/testing program.

FUNDINGS

 Josefine Hirtl & Maria Buss Stiftung 1999  Komission Onkologie 2000  FWF (P15100, P 28978-B28)  ÖNB (P9448, P10819, P13012)  Initiative Krebsforschung (UE71104017 and UE1504001)  ÖGHO Forschungsförderungspreis.

AWARDS

 Die Aventis Stiftung zur Förderung der medizinischen Forschung, 1999: Basic Fibroblast Growth Factor is Expressed by CD19/CD11c-Positive Cells in Hairy Cell Leukemia.  Erste Bank Preis/Ärztekammer f. Wien, 2001: Reconstitution of Endogenous interferon-alpha by recombinant Interferon in Hairy cell Leukemia.  Fellinger Preis, 2003: NOTCH2 is involved in the overexpression of CD23 in B-cell chronic lymphocytic leukemia.  Sanofi-Aventis Preis 2005: TGF-ß1 induces bone marrow reticulin fibrosis in hairy cell leukaemia. J. Clinic. Invest, 2004.  Paracelsus Medical University/Gastein award, 2008: Role of TGF-ß in the therapeutic effect of Radon therapy in patients with Ankylosing Spondylitis, involvement of synovial fibroblasts.  Sanofi-Aventis Preis, 2010: Targeting PI3-K/Akt/CK2 for cancer therapy

MEMBERSHIP IN SCIENTIFIC SOCIETIES

 ÖGHO

TEACHING

 UE: 591.492 Molekularbiologische Arbeiten auf dem Gebiet der Hämatologie- Onkologie, since 2001  SE: 520.097 Klinische und experimentelle Hämatologie, since 2001  Supervision of PhD and Diploma students

PROJECT MANAGEMENT

 Project leader/PI: >10 Academic projects  Contribution to >10 preclinical project in cooperation with international pharmaceutical partners.

2 SELECTED PUBLICATIONS

3 Dahl M, Meskiene I, Bögre L, Ha DT, Swoboda I, Hubmann R, Hirt H, Heberle-Bors E. The D-type alfalfa cyclin gene cycMs4 complements G1 cyclin-deficient yeast and is induced in the G1 phase of the cell cycle. Plant Cell 1995, 7:1847-57

M. Shehata, J.D. Schwarzmeier JD, S.T. Nguyen, M. Hilgarth, R. Berger, R. Hubmann, S. Kickmaier, T. Decker. Reconstitution of endogenous interferon a by recombinant interferon in hairy cell leukemia. Cancer Res, 2000, 60:5420-5426.

R. Hubmann, Schwarzmeier JD, Shehata M, Hilgarth M, Düchler M, Dettke M, Berger R: Notch2 is involved in the overexpression of CD23 in B-CLL. BLOOD 2002, 99:3742

Schwarzmeier JD, Shehata M, Hilgarth M, Marschitz I, Louda N, Hubmann R, Greil R. The role of soluble CD23 in distinguishing stable and progressive forms of B-chronic lymphocytic leukemia. Leuk Lymphoma, 2002, 43:549-54.

M. Shehata, Schwarzmeier JD, Hilgarth M, Hubmann R, Duechler M, Gisslinger H. TGF-ß1 induces bone marrow reticulin fibrosis in hairy cell leukemia. JCI, 2004, 113:676.

J.D. Schwarzmeier, R. Hubmann, M. Düchler, U. Jäger, M. Shehata. Regulation of CD23 expression by Notch2 in B-cell chronic lymphocytic leukemia. Leukemia&Lymphoma 2005, 46:157-165.

M. Duechler, M. Shehata, A. Hoelbl, M. Hilgarth, R. Hubmann. Induction of apoptosis by proteasome inhibitors in B-CLL cells is associated with downregulation of CD23 and inactivation of Notch2. Leukemia, 2005, 19:260-267.

Hubmann, R., Duchler, M., Schnabl, S., Hilgarth, M., Demirtas, D., Mitteregger, D., Hölbl, A., Vanura, K., Le, T., Look, T., Schwarzmeier, J.D., Valent, P., Jäger, U. & Shehata, M. NOTCH2 links protein kinase C delta to the expression of CD23 in chronic lymphocytic leukaemia (CLL) cells. British Journal of Haematology, 2010, 148:868- 878.

Shehata, M., Schnabl, S., Demirtas, D., Hilgarth, M., Hubmann, R., Ponath, E., Badrnya, S., Lehner, C., Hoelbl, A., Duechler, M., Gaiger, A., Zielinski, C., Schwarzmeier, J.D. & Jaeger, U. Reconstitution of PTEN activity by CK2 inhibitors and interference with the PI3-K/Akt cascade counteract the antiapoptotic effect of human stromal cells in chronic lymphocytic leukemia. Blood, 2010, 116:2513-2521

Shehata M, Demirtas D, Schnabl S, Hilgarth M, Hubmann R, Fonatsch C, Schwarzinger I, Hopfinger G, Eigenberger K, Heintel D, Porpaczy E, Vanura K, Hauswirth A, Schwarzmeier JD, Gaiger A, Stilgenbauer S, Hallek M, Bilban M, Jäger U. Sequential gene expression profiling during treatment for identification of predictive markers and novel therapeutic targets in chronic lymphocytic leukemia. Leukemia, 2010, 12:2122-2127.

Hubmann R, Hilgarth M, Schnabl, S. et al., Gliotoxin is a potent NOTCH2 transactivation inhibitor and efficiently induces apoptosis in chronic lymphocytic leukaemia (CLL) cells. British Journal of Haematology, 2013, 160:618-629.

Hubmann R, Wolfgang S, Schnabl S, Araghi M, Hilgarth M, Reiter M, Demirtas D, Zielinski C, Jäger U, & Shehata M. Gliotoxin efficiently targets nuclear NOTCH2 active cell lines of human solid tumor origin, submitted.

Hubmann R, Schnabl S, Araghi M, Hilgarth M, Reiter M, Demirtas D, Zielinski C, Jäger U, & Shehata M.Differential regulation of NOTCH family members by gliotoxin and γ-secretase inhibitors in CLL cells, submitted.