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    Leor Weinberger, PhD

    TitleAssociate Professor
    SchoolUCSF School of Medicine
    DepartmentBiochemistry and Biophysics
    Address1650 Owens St
    San Francisco CA 94107
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      Collapse Biography 
      Collapse Education and Training
      Princeton UniversityLewis-Thomas FellowMolecular Biology2007
      University of California, BerkeleyPh.D.Biophysics2004
      University of Maryland, College ParkB.Sc.Biology, Physics1998
      Collapse Awards and Honors
      2016Blavatnik Scholar
      2016Senior Investigator, Gladstone Institutes
      2013NIH Director's Pioneer Award
      2015American Institute for Mechanical and Biological Engineering (AIMBE), College of Fellows
      2013NIH/NIDA Avant Garde Award for HIV Research (deferred)
      2011Alfred P. Sloan Research Fellow
      2009NIH Director's New Innovator Award
      2009Bill & Melinda Gates Foundation, Grand Challenges Award
      2009W.M. Keck Foundation, Research Excellence Award
      2009California HIV/AIDS Foundation, Young Investigator Innovative Development Award
      2008NIH K25 Career Development Award
      2008Pew Scholar in the Biomedical Sciences
      2004Lewis Thomas Fellowship, Princeton University
      1999E. Cota-Robles Fellowship, UC Berkeley
      1999Howard Hughes Medical Institute (HHMI) Pre-Doctoral Fellowship
      1997John Prost Award, University of Maryland
      1997HHMI Undergraduate Research Fellowship, 2nd Award
      1996Maryland Distinguished Scholar
      1995HHMI Undergraduate Research Fellowship
      1993NIH FAES Fellow

      Collapse Overview 
      Collapse Overview
      Dr. Weinberger and colleagues pioneered the study of HIV’s decision circuit and demonstrated that stochastic ‘noise’ in gene expression—Brownian fluctuations arising from diffusion-limited reactions—can drive fate-selection decisions. The lab’s studies identified the molecular sources of noise in HIV, exposed the mechanisms regulating noise, and determined how feedback architectures tune noise for fate selection. The techniques developed for HIV also enabled the lab’s discovery of the first transcriptional accelerator circuit—a high-cooperativity feedback motif that enables signaling systems (e.g. inflammatory responses) to overcome a fundamental tradeoff wherein increased speed generates higher/toxic amplitude. These accelerator circuits in herpesviruses are being exploited for a new class of antiviral target.

      Collectively, the lab’s studies overturned dogma that HIV latency was a deterministic cell-driven artifact and instead showed that HIV encodes a ‘hardwired’ latency program that is evolutionarily optimized to harness noise. Gene-expression noise is now acknowledged as a major clinical barrier to reversing HIV latency and curing HIV. These studies laid the foundation for new therapeutic strategies targeting the HIV-latency circuit, including the lab’s prediction and subsequent discovery of noise-enhancer molecules. Noise enhancers potentiate transcriptional activators, substantially increasing their efficacy and ability to activate persistent (i.e., latent) HIV.

      Collapse ORNG Applications 
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      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Ali I, Ramage H, Boehm D, Dirk LM, Sakane N, Hanada K, Pagans S, Kaehlcke K, Aull K, Weinberger L, Trievel R, Schnoelzer M, Kamada M, Houtz R, Ott M. The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7. J Biol Chem. 2016 Jul 29; 291(31):16240-8. PMID: 27235396.
        View in: PubMed
      2. Rast LI, Rouzine IM, Rozhnova G, Bishop L, Weinberger AD, Weinberger LS. Conflicting Selection Pressures Will Constrain Viral Escape from Interfering Particles: Principles for Designing Resistance-Proof Antivirals. PLoS Comput Biol. 2016 May; 12(5):e1004799. PMID: 27152856.
        View in: PubMed
      3. Tanner EJ, Kirkegaard KA, Weinberger LS. Exploiting Genetic Interference for Antiviral Therapy. PLoS Genet. 2016 May; 12(5):e1005986. PMID: 27149616.
        View in: PubMed
      4. Weinberger LS. A minimal fate-selection switch. Curr Opin Cell Biol. 2015 Dec; 37:111-8. PMID: 26611210.
        View in: PubMed
      5. Rouzine IM, Weinberger AD, Weinberger LS. An evolutionary role for HIV latency in enhancing viral transmission. Cell. 2015 Feb 26; 160(5):1002-12. PMID: 25723173; PMCID: PMC4488136 [Available on 02/26/16].
      6. Razooky BS, Pai A, Aull K, Rouzine IM, Weinberger LS. A hardwired HIV latency program. Cell. 2015 Feb 26; 160(5):990-1001. PMID: 25723172; PMCID: PMC4395878 [Available on 02/26/16].
      7. Jung SY, Notton T, Fong E, Shusteff M, Weinberger LS. Spatial tuning of acoustofluidic pressure nodes by altering net sonic velocity enables high-throughput, efficient cell sorting. Lab Chip. 2015 Feb 21; 15(4):1000-3. PMID: 25563937; PMCID: PMC4450855 [Available on 02/21/16].
      8. Rouzine IM, Razooky BS, Weinberger LS. Stochastic variability in HIV affects viral eradication. Proc Natl Acad Sci U S A. 2014 Sep 16; 111(37):13251-2. PMID: 25201951; PMCID: PMC4169906.
      9. Notton T, Sardanyés J, Weinberger AD, Weinberger LS. The case for transmissible antivirals to control population-wide infectious disease. Trends Biotechnol. 2014 Aug; 32(8):400-5. PMID: 25017994.
        View in: PubMed
      10. Dar RD, Hosmane NN, Arkin MR, Siliciano RF, Weinberger LS. Screening for noise in gene expression identifies drug synergies. Science. 2014 Jun 20; 344(6190):1392-6. PMID: 24903562; PMCID: PMC4122234.
      11. Rouzine IM, Coffin JM, Weinberger LS. Fifteen years later: hard and soft selection sweeps confirm a large population number for HIV in vivo. PLoS Genet. 2014 Feb; 10(2):e1004179. PMID: 24586204; PMCID: PMC3930503.
      12. Fong EJ, Johnston AC, Notton T, Jung SY, Rose KA, Weinberger LS, Shusteff M. Acoustic focusing with engineered node locations for high-performance microfluidic particle separation. Analyst. 2014 Mar 7; 139(5):1192-200. PMID: 24448925.
        View in: PubMed
      13. Weinberger AD, Weinberger LS. Stochastic fate selection in HIV-infected patients. Cell. 2013 Oct 24; 155(3):497-9. PMID: 24243007.
        View in: PubMed
      14. Rouzine IM, Weinberger LS. Reply to "Coadaptive stability of interfering particles with HIV-1 when there is an evolutionary conflict". J Virol. 2013 Sep; 87(17):9960-2. PMID: 23943740; PMCID: PMC3754088.
      15. Gardner TJ, Bolovan-Fritts C, Teng MW, Redmann V, Kraus TA, Sperling R, Moran T, Britt W, Weinberger LS, Tortorella D. Development of a high-throughput assay to measure the neutralization capability of anti-cytomegalovirus antibodies. Clin Vaccine Immunol. 2013 Apr; 20(4):540-50. PMID: 23389931; PMCID: PMC3623408.
      16. Teng MW, Bolovan-Fritts C, Dar RD, Womack A, Simpson ML, Shenk T, Weinberger LS. An endogenous accelerator for viral gene expression confers a fitness advantage. Cell. 2012 Dec 21; 151(7):1569-80. PMID: 23260143; PMCID: PMC3552493.
      17. Rouzine IM, Weinberger LS. Design requirements for interfering particles to maintain coadaptive stability with HIV-1. J Virol. 2013 Feb; 87(4):2081-93. PMID: 23221552; PMCID: PMC3571494.
      18. Razooky BS, Gutierrez E, Terry VH, Spina CA, Groisman A, Weinberger LS. Microwell devices with finger-like channels for long-term imaging of HIV-1 expression kinetics in primary human lymphocytes. Lab Chip. 2012 Nov 7; 12(21):4305-12. PMID: 22976503; PMCID: PMC3589574.
      19. Dar RD, Razooky BS, Singh A, Trimeloni TV, McCollum JM, Cox CD, Simpson ML, Weinberger LS. Transcriptional burst frequency and burst size are equally modulated across the human genome. Proc Natl Acad Sci U S A. 2012 Oct 23; 109(43):17454-9. PMID: 23064634; PMCID: PMC3491463.
      20. Boehm D, Calvanese V, Dar RD, Xing S, Schroeder S, Martins L, Aull K, Li PC, Planelles V, Bradner JE, Zhou MM, Siliciano RF, Weinberger L, Verdin E, Ott M. BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism. Cell Cycle. 2013 Feb 1; 12(3):452-62. PMID: 23255218; PMCID: PMC3587446.
      21. Singh A, Razooky BS, Dar RD, Weinberger LS. Dynamics of protein noise can distinguish between alternate sources of gene-expression variability. Mol Syst Biol. 2012; 8:607. PMID: 22929617; PMCID: PMC3435505.
      22. Metzger VT, Lloyd-Smith JO, Weinberger LS. Autonomous targeting of infectious superspreaders using engineered transmissible therapies. PLoS Comput Biol. 2011 Mar; 7(3):e1002015. PMID: 21483468; PMCID: PMC3060167.
      23. Franz K, Singh A, Weinberger LS. Lentiviral vectors to study stochastic noise in gene expression. Methods Enzymol. 2011; 497:603-22. PMID: 21601105.
        View in: PubMed
      24. Razooky BS, Weinberger LS. Mapping the architecture of the HIV-1 Tat circuit: A decision-making circuit that lacks bistability and exploits stochastic noise. Methods. 2011 Jan; 53(1):68-77. PMID: 21167940; PMCID: PMC4096296.
      25. Singh A, Razooky B, Cox CD, Simpson ML, Weinberger LS. Transcriptional bursting from the HIV-1 promoter is a significant source of stochastic noise in HIV-1 gene expression. Biophys J. 2010 Apr 21; 98(8):L32-4. PMID: 20409455; PMCID: PMC2856162.
      26. Weinberger AD, Perelson AS, Ribeiro RM, Weinberger LS. Accelerated immunodeficiency by anti-CCR5 treatment in HIV infection. PLoS Comput Biol. 2009 Aug; 5(8):e1000467. PMID: 19680436; PMCID: PMC2715863.
      27. Singh A, Weinberger LS. Stochastic gene expression as a molecular switch for viral latency. Curr Opin Microbiol. 2009 Aug; 12(4):460-6. PMID: 19595626; PMCID: PMC2760832.
      28. Weinberger LS, Dar RD, Simpson ML. Transient-mediated fate determination in a transcriptional circuit of HIV. Nat Genet. 2008 Apr; 40(4):466-70. PMID: 18344999.
        View in: PubMed
      29. Weinberger LS, Shenk T. An HIV feedback resistor: auto-regulatory circuit deactivator and noise buffer. PLoS Biol. 2007 Jan; 5(1):e9. PMID: 17194214; PMCID: PMC1717016.
      30. Weinberger LS, Burnett JC, Toettcher JE, Arkin AP, Schaffer DV. Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Cell. 2005 Jul 29; 122(2):169-82. PMID: 16051143.
        View in: PubMed
      31. Weinberger LS, Schaffer DV, Arkin AP. Theoretical design of a gene therapy to prevent AIDS but not human immunodeficiency virus type 1 infection. J Virol. 2003 Sep; 77(18):10028-36. PMID: 12941913; PMCID: PMC224590.
      32. Rosen HR, Ribeiro RR, Weinberger L, Wolf S, Chung M, Gretch DR, Perelson AS. Early hepatitis C viral kinetics correlate with long-term outcome in patients receiving high dose induction followed by combination interferon and ribavirin therapy. J Hepatol. 2002 Jul; 37(1):124-30. PMID: 12076871.
        View in: PubMed
      33. Mohri H, Perelson AS, Tung K, Ribeiro RM, Ramratnam B, Markowitz M, Kost R, Hurley A, Weinberger L, Cesar D, Hellerstein MK, Ho DD. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J Exp Med. 2001 Nov 5; 194(9):1277-87. PMID: 11696593; PMCID: PMC2195973.
      34. Shiratori Y, Perelson AS, Weinberger L, Imazeki F, Yokosuka O, Nakata R, Ihori M, Hirota K, Ono N, Kuroda H, Motojima T, Nishigaki M, Omata M. Different turnover rate of hepatitis C virus clearance by different treatment regimen using interferon-beta. J Hepatol. 2000 Aug; 33(2):313-22. PMID: 10952250.
        View in: PubMed
      35. Jin X, Bauer DE, Tuttleton SE, Lewin S, Gettie A, Blanchard J, Irwin CE, Safrit JT, Mittler J, Weinberger L, Kostrikis LG, Zhang L, Perelson AS, Ho DD. Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med. 1999 Mar 15; 189(6):991-8. PMID: 10075982; PMCID: PMC2193038.
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