DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 8,748,464 B2 Verdin Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 8,748,464 B2 Verdin Et Al USOO8748464B2 (12) United States Patent (10) Patent No.: US 8,748,464 B2 Verdin et al. (45) Date of Patent: Jun. 10, 2014 (54) USE OF SIRT1 ACTIVATORS OR INHIBITORS Ott et al., “Immune hyperactivation of HIV-1-infected T cells medi TO MODULATE AN IMMUNE RESPONSE ated by Tat and the CD28 pathway.” (1997) Science 275: 1481-1485. Nayagam et al., “SIRT1 modulating compounds from high-through (75) Inventors: Eric M. Verdin, San Francisco, CA put Screening as anti-inflammatory and insulin-sensitizing agents.” (US); Melanie Ott, San Francisco, CA (2006) J. Biomol. Screening 11:959-967. (US); Hye-Sook Kwon, San Mateo, CA Ott, M. “Role of SIRT1 in T cell Hyperacitivation during HIV infec (US); Hyungwook Lim, San Francisco, tion California HIV/AIDS Research Program.” 2008 http://chrp. ucop.edu/funded research/abstracts/2007 ott.html (2007), para CA (US) 1-3. Feige et al., “Specific SIRT1 Activation Mimics Low Energy Levels (73) Assignee: The J. David Gladstone Institutes, San and Protects against Diet-Induced Metabolic Disorders by Enhanc Francisco, CA (US) ing Fat Oxidation.” (2008) Cell Metabolism 8:347-358. Sakamoto, K. “Silencing Metabolic Disorders by Novel SIRT1 Acti (*) Notice: Subject to any disclaimer, the term of this vators.” (2008) Cell Metabolism 7:3-4. patent is extended or adjusted under 35 Pacholec et al., “SRT1720, SRT2183, SRT1460, and Resveratrol are U.S.C. 154(b) by 519 days. not Direct Activators of SIRT1. Published on Jan. 8, 2010 as Manu script M109.088682 The latest version is at http://www.jbc.org/cgi/ (21) Appl. No.: 12/838,247 doi/10.1074/bc.M109.088.682–25 pages. Sundrud et al., “Synergistic and combinatorial control of T cell (22) Filed: Jul. 16, 2010 activation and differentiation by transcription factors.” ScienceDirect www.sciencedirect.com, Current Opinion in Immunology (2010) (65) Prior Publication Data 22:1-7. Tao et al., “Deacetylase inhibition promotes the generation and func US 2010/0330114A1 Dec. 30, 2010 tion of regulatory T cells.” (2007) Nat. Med. 13 (11): 1299-1307. Saouaf et al., “Deacetylase inhibition increases regulatory T cell Related U.S. Application Data function and decreases incidence and severity of collagen-induced arthritis.” (2009) Exp. Mol. Pathol. 87:99-104. (63) Continuation-in-part of application No. Van Loosdregt et al., “Regulation of Treg functionality by acetyla PCT/US2009/000761, filed on Feb. 5, 2009. tion-mediated Foxp3 protein stabilization” (2010) Blood (60) Provisional application No. 61/026,997, filed on Feb. 115(5):965-974. 7, 2008. Wang et al., “Using histone deacetylase inhibitors to enhance Foxp3+ regulatory T-cell function and induce allograft tolerance.” (2009) Immunol. Cell Biol. 87: 195-202. (51) Int. Cl. Pagans, et al. “SIRT1 Regulates HIV Transcription via TAT AOIN 43/78 (2006.01) Deacetylation”. PLoS Biology, Feb. 2005, vol. 3, Issue 2, pp. 0210 A 6LX3/535 (2006.01) O220. (52) U.S. Cl. USPC ...................... 514/366; 514/229.5: 514/233.2 * cited by examiner (58) Field of Classification Search USPC .......................................................... 514/366 Primary Examiner — Sreeni Padmanabhan See application file for complete search history. Assistant Examiner — Timothy E. Betton (74) Attorney, Agent, or Firm — Paula A. Borden; (56) References Cited Bozicevic, Field & Francis LLP. U.S. PATENT DOCUMENTS (57) ABSTRACT 7,345,178 B2* 3/2008 Nunes et al. .................. 548.154 The present disclosure provides a method of increasing an 2005/02093OO A1 9/2005 Napper et al. 2007/0043050 A1 2/2007 Nunes et al. immune response in an individual, the method involving 2007/0105109 A1 5/2007 Geesaman et al. administering to an individual in need thereof an inhibitor of 2007/O1900.73 A1 8, 2007 Tucket al. SIRT1. The present disclosure provides a method of reducing 2008.O255382 A1 10/2008 Andrus et al. an immune response, e.g., to treat chronic immune hyperac 2009/0012080 A1 1/2009 Bemis et al. tivity, the method generally involving administering to an 2010 OO61984 A1 3/2010 Greene et al. individual in need thereofan activator of SIRT1. The present OTHER PUBLICATIONS disclosure provides a method of modulating activation and differentiation of CD4 T cells. Milne et al "Small rinoiecuie activators of SIRT1 as therapeutics for the treatment of type 2 diabetes.” (2007) Nature 450:712-716. 7 Claims, 13 Drawing Sheets U.S. Patent Jun. 10, 2014 Sheet 3 of 13 US 8,748.464 B2 **** G. 3A -3- 388: 8:8: (S. 33. 38. 8:8 :::::: 8:388: 8:8: tá G. 3C }& U.S. Patent Jun. 10, 2014 Sheet 4 of 13 US 8,748.464 B2 $¢£. 383. ??ž#$ ********* **x X: 8 E: i:S U.S. Patent Jun. 10, 2014 Sheet 7 of 13 US 8,748.464 B2 :::: immune &:x::::::: rG. A *::::::::: -: x88&iw888 risescripters G. B. U.S. Patent Jun. 10, 2014 Sheet 8 of 13 US 8,748.464 B2 8:8 {{}{} {}i &8888.888.888 3. 8:::::: w :- :- :- & Eric-tat-Gre Six 383 38 - --- 3.x: 8 U.S. Patent Jun. 10, 2014 Sheet 10 of 13 US 8,748.464 B2 38:33:3, 3. -- s : sa. & -8- -- U.S. Patent Jun. 10, 2014 Sheet 12 of 13 US 8,748.464 B2 {?}¿zººxaÅ???ž3§3)********&&&&%-'%.«----- ****************************************************************? G. 2A are :::::::: U.S. Patent Jun. 10, 2014 Sheet 13 of 13 US 8,748.464 B2 ***************§…*,** US 8,748,464 B2 1. 2 USE OF SIRT1 ACTIVATORS OR INHIBITORS individual in need thereofan activator of SIRT1. The present TO MODULATE AN IMMUNE RESPONSE disclosure provides a method of modulating activation and differentiation of CD4 T cells. CROSS-REFERENCE BRIEF DESCRIPTION OF THE DRAWINGS This application is a continuation-in-part of International Patent Application No. PCT/US2009/000761, which claims FIGS. 1A-F depict data showing the effect of Tat and the benefit of U.S. Provisional Patent Application No. 61/026, nicotinamide on T cell hyperactivation. 997, filed Feb. 7, 2008, which applications are incorporated FIGS. 2A-D depict the Tat-mediated superinduction of herein by reference in their entirety. 10 NF-kB-responsive genes. FIGS. 3A-C depicts the effect of Tat on the inhibitory effect STATEMENT REGARDING FEDERALLY of SIRT1 on NK-K-B-responsive promoters. SPONSORED RESEARCH FIGS. 4A-E depict binding of Tat to the acetyl lysine binding site in SIRT1. This invention was made with government Support under 15 FIGS.5A-D depict the effect of Tat on SIRT1 deacetylase grant no. R01 A1067.118-01A awarded by the National Insti activity. tutes of Health. The government has certain rights in the FIGS. 6A-C depict the effect of hyperacetylation of p85 by invention. Tat on T-cell hyperactivation. BACKGROUND FIGS. 7A and 7B depict a model for Tat effects on SIRT1 deacetylase activity, T-cell activation, and HIV transcription. Immune activation is a hallmark of human immunodefi FIGS. 8A and 8B depict the effect of SIRT1 activators on ciency virus-1 (HIV-1) infection and a significant factor that Tat-mediated T cell hyperactivation. promotes continuous viral replication and CD4+ T-cell deple FIGS. 9A and 9B depict the effect of SIRT1 on induced tion. In HIV-infected individuals, levels of circulating activa 25 Treg (iTreg) differentiation. tion markers correlate with accelerated disease progression FIGS. 10A-D depict interaction of SIRT1 with FoxP3, and and shortened survival. HIV infection is critically dependent the effect of inhibition of SIRT1 deacetylase activity on on the activated state of CD4+ T cells since the virus cannot acetylation of FoxP3. replicate efficiently in resting T cells. Quiescent T cells in FIGS. 11A-D depict destabilization of FoxP3 protein via blood are refractory to infection because of blocks at the level 30 deacetylation by SIRT1. of reverse transcription and proviral integration. In addition, FIGS. 12A and 12B depict the effect of inhibition of SIRT1 T-cell activation enhances viral transcription through the acti activity on differentiation of iTreg cells and FoxP3 expression Vation of various transcription factors, notably nuclear factor in nTreg cells. KB (NF-kB). FIG. 13 depicts an alignment of amino acid sequences of SIRT1 is a mammalian homologue of the yeast transcrip 35 tional repressor silent information regulator 2 (Sir2), an human FoxP3 (GenBank Accession Nos. NP 054728 and important factor governing longevity in yeast. Like Sir2. NM 014009), mouse FoxP3 (GenBank Accession Nos. SIRT1 requires nicotinamide adenine dinucleotide (NAD') NM 054039 and NP 473380), and cow FoxP3 (GenBank as a cofactor, which links its activity to the metabolic state of Accession Nos. NM 001045933 and NP 001039398). the cell. In addition to its enzymatic activity on histone Sub 40 strates in vitro, recent experimental evidence suggests that DEFINITIONS SIRT1 predominantly targets nonhistone proteins for 99 &g deacetylation. It has been reported that Tat is a substrate for As used herein, the terms “treatment,” “treating, and the the deacetylase activity of SIRT1. Acetylation of lysine 50 like, refer to obtaining a desired pharmacologic and/or physi (K50) in Tat is mediated by the histone acetyltransferase 45 ologic effect. The effect may be prophylactic in terms of activities of p300 and human GCN5 and generates binding completely or partially preventing a disease or symptom sites for the bromodomains of PCAF and Brg1. SIRT1 binds thereof and/or may be therapeutic in terms of a partial or and deacetylates Tat at K50, a process necessary to recycle complete cure for a disease and/or adverse affect attributable nonacetylated Tat protein for binding to TAR RNA and the to the disease. “Treatment’, as used herein, covers any treat cellular positive transcription elongation factor b (P-TEFb). 50 ment of a disease in a mammal, e.g., in a human, and includes: Literature (a) preventing the disease from occurring in a Subject which Milne et al., (2007) Nature 450:712-716; U.S.
Load more

Recommended publications
  • Eric Verdin, MD
    CURRICULUM VITAE Eric Verdin, MD Work Address The Buck Institute for Research on Aging 8001 Redwood Blvd. Novato, CA 94945 Office Phone: (415) 209-2250 Cell Phone: (415) 305-9208 Email: [email protected] Biographical Data Birthplace: Belgium Citizenship: Belgium, USA Education MD, University of Liège Liège, Belgium, 1982 Visiting Student, Harvard Medical School Boston, MA, 1981 B.S. in Medical Sciences, University of Liège Liège, Belgium, 1978 Research Positions 2016- Present CEO & President, The Buck Institute for Research on Aging, Novato, CA 2016- Present Adjunct Professor, Leonard Davis School of Gerontology, University of Southern California, Los Angeles 2004-2016 Associate Director, Gladstone Institutes, San Francisco, CA 1998- Present Professor, University of California, San Francisco, CA 1997- 2016 Senior Investigator, Gladstone Institute, San Francisco, CA 1997 Professor, The Picower Institute for Medical Research, Manhasset, NY 1993-1997 Associate Professor, The Picower Institute for Medical Research, Manhasset, NY 1990-1993 Senior Staff Fellow, NIH, Bethesda, MD 1 1987-1990 Assistant Professor, Free University of Brussels, Belgium 1984-1987 Postdoctoral Fellowship, Harvard Medical School, Elliott P. Joslin Research Laboratory, Boston, MA (Laboratories of C. Ronald Kahn and Bernard Fields) 1983-1984 Intern in Medicine, University of Massachusetts, Worcester, MA 1982-1983 Research Intern, University of Liège, Department of Internal Medicine, Liège, Belgium Memberships & Activities Member, Board of Directors, Bay Area
    [Show full text]
  • CRISPR-Based COVID-19 Smartphone Test in Development
    News & Analysis Biotech Innovations CRISPR-Based COVID-19 Smartphone Predicting COVID-19 Outcomes any symptoms, to make sure resources are Test in Development in Emergency Department Patients appropriately allocated,” Fred Kwon, PhD, A simplified point-of-care assay that turns a A new artificial intelligence algorithm uses the study’s lead author, said in a statement. smartphone into a fluorescence micro- chest x-ray severity scores and clinical vari- The chest x-ray severity scores alone could scope could expand coronavirus disease ables collected during emergency depart- be useful. “We are working to incorporate 2019(COVID-19)testingcapability,research- ment (ED) visits to predict whether pa- this algorithm-generated severity score into ers reported in a study in Cell. tients with coronavirus disease 2019 the clinical workflow to inform treatment de- The assay, which uses clustered (COVID-19) will be intubated or will die. If fur- cisions and flag high-risk patients in the fu- regularly interspaced short palindromic ther validated in larger studies with addi- ture,” Kwon said. repeats (CRISPR) gene editing technol- tional patient populations, the proof-of- ogy, emits a fluo- concept model, described in Radiology: Phone Apps and Wearable Trackers rescent signal in Artificial Intelligence, could be used to ap- Modestly Improve Activity Viewpoint page 529 the presence of propriately triage ED patients before they Smartphone fitness applications and wear- the novel corona- become seriously ill with COVID-19. able activity trackers seem to have a small to virus’s RNA. A smartphone camera can moderate positive effect on physical activ- detect this signal directly, without amplifi- ity,a systematic review and meta-analysis of cation of the viral genome used in most randomized trials found.
    [Show full text]
  • Smartphone Apps Test and Track Infectious Diseases
    Work / Technology & tools ADAPTED FROM GETTY FROM ADAPTED SMARTPHONE APPS TEST AND TRACK INFECTIOUS DISEASES The prevalence, power and portability of smartphones make them valuable tools for pathogen monitoring and citizen science. By Sandeep Ravindran ebojyoti Chakraborty took just a quantify bands using machine learning, and to deploy, and they get real-time insights few months to develop a COVID-19 export the results to the cloud. Called TOPSE1, directly from people on the ground,” says diagnostic test that worked in his their app laid the foundation for a test that has John Brownstein, a computational epide- lab; the challenge was to optimize it now been approved by the Drugs Controller miologist at Boston Children’s Hospital in for the field. General of India. “You can actually do this Massachusetts. “That kind of data can out- DBased on the gene-editing technology test in local pathology labs in places that are pace what traditional surveillance provides.” CRISPR, the test produces a band on a paper resource-limited,” Chakraborty says. “Per- strip if viral RNA is present. But Chakraborty, haps one day it can be done even at home.” Portable epidemiology who heads an RNA biology group at the Insti- The billions of smartphones in use world- Smartphone science didn’t start with tute of Genomics and Integrative Biology in wide offer unprecedented opportunities COVID-19. But the pandemic has spurred New Delhi, says he and his colleagues couldn’t for disease tracking, diagnostics and citizen researchers to fast-track citizen-science always agree on whether a faint band counted science, as Chakraborty learnt.
    [Show full text]
  • Holmes Washington 0250E 22
    ©Copyright 2020 Daniel Holmes Identification of Targetable Vulnerabilities During Latent KSHV Infection Daniel Holmes A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2020 Reading Committee: Michael Lagunoff, Chair Adam Philip Geballe Jason G Smith Program Authorized to Offer Degree: Department of Microbiology University of Washington Abstract Identification of Targetable Vulnerabilities During Latent KSHV Infection Daniel Holmes Chair of the Supervisory Committee: Professor Michael Lagunoff Department of Microbiology Viruses are defined as obligate intracellular parasites that require host processes to repli- cate. Latent virus life cycles are no exception to this definition, as viruses are still reliant on host machinery for continued proliferation and maintenance of viral genomes, even in the absence of lytic replication. In this thesis, I used essentiality screening to identify host factors on which Kaposi's Sarcoma Associated Herpesvirus (KSHV) relies for the proliferation and survival of latently infected cells. KSHV is the etiological agent of Kaposi's Sarcoma (KS), an endothelial cell-based tumor where more than 90% of the endothelial cells in the tumor are latently infected with KSHV. While traditional therapies for herpesviruses target lytic replication, the prevalence of latency in KS necessitates exploration of options for intervening in this stage of the viral life cycle. I performed CRISPR/Cas9 screening using lentiviral vec- tors encoding a library of single guide RNAs (sgRNAs) targeting every protein coding gene in the human genome. I compared mock infected and KSHV infected endothelial cells eight days post infection to identify genes essential to latent KSHV infection.
    [Show full text]
  • Of 35 STOCHASTIC GENE EXPRESSION in A
    STOCHASTIC GENE EXPRESSION IN A LENTIVIRAL POSITIVE FEEDBACK LOOP: HIV-1 TAT FLUCTUATIONS DRIVE PHENOTYPIC DIVERSITY Leor S. Weinberger1§*, John C. Burnett3, Jared E. Toettcher2, Adam P. Arkin2,4*‡, and David V. Schaffer3‡ Biophysics Graduate Group1, Depts. of Bioengineering2, The Howard Hughes Medical Institute2 Chemical Engineering3, and the Helen Wills Neuroscience Institute3, University of California, Berkeley, CA 94720 and Physical Biosciences Division4, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 * corresponding authors: [email protected], Tel: (609) 258-6785, Fax: (609) 258-1704 [email protected], Tel: (510) 495-2116, Fax (510) 486-6129 ‡ these authors contributed equally to this work Running Title: Stochastics in HIV-1 transactivation Manuscript Information 50 text pages (abstract, text body, and references) 6 Figures, 1 Table, 13 Equations Character Count (text, figure legends, methods, references): 54,548 Abstract: 143 Words Abbreviations: LTR. Long Terminal Repeat; IRES, Internal Ribosomal Entry Site; LGIT, LTR-GFP-IRES-Tat (an HIV-1 derived lentiviral vector); LG, LTR-GFP (an HIV-1 derived lentiviral vector); ODE, Ordinary Differential Equation; HERV, Human Endogenous Retrovirus; RNAPII, RNA Polymerase II; MOI, Multiplicity of Infection; GFP, Green Fluorescent Protein; TNF!, Tumor Necrosis Factor !; PMA, Phorbol Myristate Acetate; TSA, Trichostatin A; SINE, Short Interspersed Nuclear Element; LINE, Long Interspersed Nuclear Element; PheB, Phenotypic Bifurcation; PTEFb, Positive Transcriptional Elongation Factor b; Cdk9, Cyclin dependent kinase 9; RFU, Relative Fluorescence Units. SUPPLEMENTARY INFORMATION ATTACHED. § Current address: Dept. of Molecular Biology, Princeton University, Princeton, NJ 08544- 1014 Page 1 of 35 SUMMARY HIV-1 Tat transactivation is vital for completion of the viral lifecycle and has been implicated in determining proviral latency.
    [Show full text]
  • SARS-Cov-2 Infection of Human Ipsc-Derived Cardiac Cells Predicts Novel Cytopathic Features in Hearts of COVID-19 Patients
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.25.265561; this version posted September 12, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients Juan A. Pérez-Bermejo*1, Serah Kang*1, Sarah J. Rockwood*1, Camille R. Simoneau*1,2, David A. Joy1,3, Gokul N. Ramadoss1,2, Ana C. Silva1, Will R. Flanigan1,3, Huihui Li1, Ken Nakamura1,4, Jeffrey D. Whitman5, Melanie Ott†,1, Bruce R. Conklin†,1,6,7,8, Todd C. McDevitt†1,9 * These authors contributed equally to this work. † Co-corresponding authors. 1 Gladstone Institutes, San Francisco, CA 2 Biomedical Sciences PhD Program, University of California, San Francisco, CA 3 UC Berkeley UCSF Joint Program in Bioengineering, Berkeley, CA 4 UCSF Department of Neurology, San Francisco, CA 5 UCSF Department of Laboratory Medicine, San Francisco, CA 6 Innovative Genomics Institute, Berkeley, CA 7 UCSF Department of Ophthalmology, San Francisco, CA 8 UCSF Department of Medicine, San Francisco, CA 9 UCSF Department of Bioengineering and Therapeutic Sciences, San Francisco, CA ABSTRACT Although COVID-19 causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human iPSC-derived heart cells to SARS-CoV-2 revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes.
    [Show full text]
  • How Cells Hush a Viral Invader
    NEWS & VIEWS RESEARCH from an EOF analysis of SST anomalies in the Yoo-Geun Ham is in the Department of 4. Ham, Y.-G. & Kug, J.-S. Clim. Dyn. 39, 383–398 tropical Pacific, which yields two dominant Oceanography, Chonnam National University, (2012). 5. Takahashi, K., Montecinos, A., Goubanova, K. & principal-component time series and two Gwangju, South Korea. Dewitte, B. Geophys. Res. Lett. 38, L10704 (2011). 5 associated anomaly patterns . They then use e-mail: [email protected] 6. An, S.-I., Kug, J.-S., Ham, Y.-G. & Kang, I.-S. J. Clim. a linear combination of these principle com- 21, 3–21 (2008). 1. Collins, M. et al. Nature Geosci. 3, 391–397 (2010). 7. Cai, W. et al. Nature Clim. Change 5, 132–137 ponents and patterns to identify an individual 2. Cai, W. et al. Nature Clim. Change 5, 849–859 (2015). EP-El Niño centre for each climate model. (2015). 8. Yeh, S.-W. et al. Nature 461, 511–514 (2009). Finally, they introduce an EP-El Niño index 3. Cai, W. et al. Nature 564, 201–206 (2018). 9. Rayner, N. A. et al. J. Geophys. Res. 108, 4407 (2003). for each model, which represents the model’s EP-El Niño centre and pattern. The authors report that a reasonable consensus emerges: VIROLOGY 24 of the 34 available models (71%) predict an increase in EP-El Niño SST variability under a climate-change scenario (known as RCP8.5) that assumes greenhouse-gas emissions will How cells hush continue to rise steeply throughout the twenty- first century.
    [Show full text]
  • CURRICULUM VITAE Eric Verdin
    CURRICULUM VITAE Eric Verdin, MD Work Address The Buck Institute for Research on Aging 8001 Redwood Blvd. Novato, CA 94945 Office Phone: (415) 209-2250 Cell Phone: (415) 305-9208 Email: [email protected] Biographical Data Birthplace: Belgium Citizenship: Belgium, USA Education MD, University of Liège Liège, Belgium, 1982 Visiting Student, Harvard Medical School Boston, MA, 1981 B.S. in Medical Sciences, University of Liège Liège, Belgium, 1978 Positions 2016- Present CEO & President, The Buck Institute for Research on Aging, Novato, CA 2016-Present Member, Board of Trustees, Buck Institute for Research on Aging 2016-Present Director, Paul F. Glenn Center for Aging Research at the Buck Institute 2016- Present Adjunct Professor, Leonard Davis School of Gerontology, University of Southern California, Los Angeles 2016-Present Adjunct Professor, University of California, San Francisco, CA 2004-2016 Associate Director, Gladstone Institutes, San Francisco, CA 1998- 2016 Professor, University of California, San Francisco, CA 1997- 2016 Senior Investigator, Gladstone Institute, San Francisco, CA 1997 Professor, The Picower Institute for Medical Research, Manhasset, NY 1993-1997 Associate Professor, The Picower Institute for Medical Research, Manhasset, NY 1990-1993 Senior Staff Fellow, NIH, Bethesda, MD 1987-1990 Assistant Professor, Free University of Brussels, Belgium 1984-1987 Postdoctoral Fellowship, Harvard Medical School, Elliott P. Joslin Research Laboratory, Boston, MA (Laboratories of C. Ronald Kahn and Bernard Fields) 1983-1984
    [Show full text]
  • 2020 Blum Center for Developing Economies MISSION
    Blum Center for Developing Economies University of California, Berkeley 100 Blum Hall #5570, Berkeley, CA 94720 Educating Changemakers and Fostering Innovative blumcenter.berkeley.edu | 510.643.5316 Solutions to Global Problems | 2020 © 2020 Blum Center for Developing Economies MISSION The Blum Center for Developing Economies at UC Berkeley leverages the talent, enthusiasm, and energy of the campus community to address urgent societal challenges globally and locally. We empower students, faculty, and researchers to build a more sustainable, just, and equitable world. CONTENTS 1 Mission 3 From the Founder 4 From the Faculty Director 6 From the Education Director 8 From the Research Director 10 Global Poverty and Practice 12 Development Engineering/InFEWS 14 Big Ideas Contest 16 Blum Center Faculty 18 Board of Trustees 20 Blum Center Funders and Network The Berkeley-Darfur Stove requires less than half the fuel of traditional cooking methods, reducing the need to trade food rations for fuel and decreasing women’s This issue is dedicated to the memory of Blum Center exposure to violence while collecting fi rewood. Senior Fellow Dr. Bertram Lubin (1939-2020). 1 FROM THE FOUNDER Overcoming Poverty Reduction Setbacks wenty twenty was a terrible year in so many ways, but especially for low-income developing countries. Much has been written about the need for the international commu- nity to enable LIDCs to tackle the pandemic and recover strongly — about the need to guarantee essential health Tsupplies, protect critical supply chains, en- sure that developing economies can fi nance critical spending, restructure debt to restore sustainability, and keep sight of the United Nations Sustainable Development Goals.
    [Show full text]
  • Final Programme
    Programme Saturday 25 August 2018 15:00 - 18:00 Arrival and Registration ATC Registration Desk 16:30 - 17:30 Pre-Conference Workshop ATC Courtyard Seminar Room 18:00 - 18:15 Welcome and Opening Remarks ATC Auditorium 18:15 - 20:00 Session 1 Chair: Eileen Furlong, EMBL Heidelberg, Germany ATC Auditorium 18:15 - 18:35 FIREnano and ChromEMT: Visualizing the structural basis 1 of gene activation and silencing in the nucleus Clodagh O'Shea Salk Institute for Biological Studies, United States of America 18:35 - 18:55 Gene Expression Within the Context of a Topologically Associating Domain 2 Douglas Higgs MRC Weatherall Institute of Molecular Medicine, University of Oxford , United Kingdom 18:55 - 19:10 RNA-mediated regulation of chromatin complexes 3 Roberto Bonasio University of Pennsylvania, United States of America 19:10 - 19:25 Decoding the chromatin proteome of a single genomic 4 locus by DNA sequencing Fred van Leeuwen Netherlands Cancer Institute, The Netherlands 19:25 - 19:45 Epigenetic Regulation of HIV Transcription 5 Melanie Ott Gladstone Institutes, University of California, San Francisco, United States of America Page 5 EMBL Conference: Transcription and Chromatin 19:45 - 20:05 A sequence anomaly of the MLL promoter imposes a 6 transcription factor addiction in leukemia Christopher Vakoc Cold Spring Harbor Laboratory, United States of America 20:05 - 21:30 Dinner EMBL Canteen 21:30 - 23:00 Welcome Reception ATC Auditorium Foyer and ATC Rooftop Lounge Page 6 Programme Sunday 26 August 2018 09:00 - 12:40 Session 2 Co-Chairs: Peter
    [Show full text]
  • New CRISPR-Based Test for COVID-19 Uses a Smartphone Camera 5 December 2020
    New CRISPR-based test for COVID-19 uses a smartphone camera 5 December 2020 spread the virus. In a new study published in the scientific journal Cell, the team from Gladstone, UC Berkeley, and UCSF has outlined the technology for a CRISPR- based test for COVID-19 that uses a smartphone camera to provide accurate results in under 30 minutes. "It has been an urgent task for the scientific community to not only increase testing, but also to provide new testing options," says Melanie Ott, MD, Ph.D., director of the Gladstone Institute of Virology The new COVID-19 test uses CRISPR gene-editing and one of the leaders of the study. "The assay we technology and a smartphone to provide a positive or developed could provide rapid, low-cost testing to negative test result and measure viral load. Credit: help control the spread of COVID-19." Gladstone Institutes The technique was designed in collaboration with UC Berkeley bioengineer Daniel Fletcher, Ph.D., as well as Jennifer Doudna, Ph.D., who is a senior Imagine swabbing your nostrils, putting the swab in investigator at Gladstone, a professor at UC a device, and getting a read-out on your phone in Berkeley, president of the Innovative Genomics 15 to 30 minutes that tells you if you are infected Institute, and an investigator of the Howard Hughes with the COVID-19 virus. This has been the vision Medical Institute. Doudna recently won the 2020 for a team of scientists at Gladstone Institutes, Nobel Prize in Chemistry for co-discovering University of California, Berkeley (UC Berkeley), CRISPR-Cas genome editing, the technology that and University of California, San Francisco underlies this work.
    [Show full text]
  • Download the PDF Here
    3/3 September 2017 Volume 3 · Supplement 3 · September 2017 Journal of Virus Eradication ISSN 2055-66-40 – Print | ISSN 2055-66-59 – Online An online open-access journal published by Mediscript Ltd www.viruseradication.com Editors Jintanat Ananworanich (USA) Abstracts of the HIV Cure and Reservoir Margaret Johnson (UK) Sabine Kinloch-de Loës (UK) Symposium 2017 Editorial Board 11–12 September 2017 Nicolas Chomont (Canada) Ghent, Belgium Steven Deeks (USA) Geoff Dusheiko (UK) Stably integrated HIV inside the host cell genome is considered the final Sarah Fidler (UK) Paul Griffiths (UK) hurdle to cure one of the most important infectious diseases humans have ever Alain Lafeuillade (France) faced. The latent HIV reservoir is able to refuel infection once the treatment is Nelson Michael (USA) Jürgen Rockstroh (Germany) stopped and therefore a better understanding of both the composition and the Irini Sereti (USA) size of the reservoir is important to aid the development of cure strategies as Janet Siliciano (USA) well as to monitor the efficacy of therapeutic interventions to reduce the HIV Robert Siliciano (USA) Guido Silvestri (USA) reservoir. Our symposium will comprehensively summarise the state of the art Linos Vandekerckhove (Belgium) in HIV cure strategies and diagnostic tools to monitor therapeutic interventions Editorial Panel and an international expert panel will guide the audience through the latest David Asboe (UK) developments in the HIV cure field, focusing on reservoir characterisation and Georg Behrens (Germany) novel clinical
    [Show full text]