Leor Weinberger, PhD

InstitutionUniversity of California San Francisco
DepartmentBiochemistry and Biophysics
Address1650 Owens St
San Francisco CA 94107
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    Collapse Biography 
    Collapse Education and Training
    Princeton UniversityLewis-Thomas Fellow2007Molecular Biology
    University of California, BerkeleyPh.D.2004Biophysics
    University of Maryland, College ParkB.Sc.1998Biology, Physics
    Collapse Awards and Honors
    2017William and Ute Bowes Distinguished Professor
    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 Research 
    Collapse Research Activities and Funding
    Experiment &Theory to Test an Evolutionary Fitness Role for Lentiviral Latency
    NIH/NIAID R21AI109611Jul 15, 2014 - Jun 30, 2016
    Role: Principal Investigator
    Stochastic Gene Expression in Retroviral Latency
    NIH/NIAID R01AI109593Jun 1, 2014 - May 31, 2019
    Role: Principal Investigator
    Evolvable 'Resistance-Proof' Therapies
    NIH/NIDCR DP1DE024408Sep 30, 2013 - Jul 31, 2018
    Role: Principal Investigator
    Martin Delaney Collaboratory to Eradicate HIV-1 Infection
    NIH U19AI096113Jul 8, 2011 - Jun 30, 2016
    Role: Co-Investigator
    Global innate immune responses to HIV-1 infection
    NIH P01AI090935Aug 15, 2010 - Jul 31, 2015
    Role: Co-Investigator
    Developing Transmissible Antivirals by Exploiting Gene-Expression Circuitry
    NIH DP2OD006677Sep 30, 2009 - Aug 31, 2014
    Role: Principal Investigator
    How Feedback Circuitry Drives Phenotype Switching in a Human Herpesvirus
    NIH/NIGMS K25GM083395Jun 5, 2008 - Jun 30, 2013
    Role: Principal Investigator

    Collapse ORNG Applications 
    Collapse Websites

    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. Hansen MMK, Wen WY, Ingerman E, Razooky BS, Thompson CE, Dar RD, Chin CW, Simpson ML, Weinberger L. A Post-Transcriptional Feedback Mechanism for Noise Suppression and Fate Stabilization. Cell. 2018 May 04. PMID: 29754821.
      View in: PubMed
    2. Saykally VR, Rast LI, Sasaki J, Jung SY, Bolovan-Fritts C, Weinberger L. A Bioreactor Method to Generate High-titer, Genetically Stable, Clinical-isolate Human Cytomegalovirus. Bio Protoc. 2017 Nov 05; 7(21). PMID: 29226181.
      View in: PubMed
    3. Razooky BS, Cao Y, Hansen MMK, Perelson AS, Simpson ML, Weinberger L. Nonlatching positive feedback enables robust bimodality by decoupling expression noise from the mean. PLoS Biol. 2017 Oct; 15(10):e2000841. PMID: 29045398.
      View in: PubMed
    4. Pai A, Weinberger L. Fate-Regulating Circuits in Viruses: From Discovery to New Therapy Targets. Annu Rev Virol. 2017 Sep 29; 4(1):469-490. PMID: 28800289.
      View in: PubMed
    5. Aull KH, Tanner EJ, Thomson M, Weinberger L. Transient Thresholding: A Mechanism Enabling Noncooperative Transcriptional Circuitry to Form a Switch. Biophys J. 2017 Jun 06; 112(11):2428-2438. PMID: 28591615.
      View in: PubMed
    6. Dar RD, Shaffer SM, Singh A, Razooky BS, Simpson ML, Raj A, Weinberger L. Transcriptional Bursting Explains the Noise-Versus-Mean Relationship in mRNA and Protein Levels. PLoS One. 2016; 11(7):e0158298. PMID: 27467384; PMCID: PMC4965078.
    7. 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 07 29; 291(31):16240-8. PMID: 27235396.
      View in: PubMed
    8. Rast LI, Rouzine IM, Rozhnova G, Bishop L, Weinberger AD, Weinberger L. Conflicting Selection Pressures Will Constrain Viral Escape from Interfering Particles: Principles for Designing Resistance-Proof Antivirals. PLoS Comput Biol. 2016 05; 12(5):e1004799. PMID: 27152856; PMCID: PMC4859541.
    9. Tanner EJ, Kirkegaard KA, Weinberger L. Exploiting Genetic Interference for Antiviral Therapy. PLoS Genet. 2016 May; 12(5):e1005986. PMID: 27149616; PMCID: PMC4858160.
    10. Weinberger L. A minimal fate-selection switch. Curr Opin Cell Biol. 2015 Dec; 37:111-8. PMID: 26611210.
      View in: PubMed
    11. Dar RD, Razooky BS, Weinberger L, Cox CD, Simpson ML. The Low Noise Limit in Gene Expression. PLoS One. 2015; 10(10):e0140969. PMID: 26488303; PMCID: PMC4619080.
    12. Rouzine IM, Weinberger AD, Weinberger L. An evolutionary role for HIV latency in enhancing viral transmission. Cell. 2015 Feb 26; 160(5):1002-1012. PMID: 25723173.
      View in: PubMed
    13. Razooky BS, Pai A, Aull K, Rouzine IM, Weinberger L. A hardwired HIV latency program. Cell. 2015 Feb 26; 160(5):990-1001. PMID: 25723172.
      View in: PubMed
    14. Jung SY, Notton T, Fong E, Shusteff M, Weinberger L. 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.
    15. Rouzine IM, Razooky BS, Weinberger L. 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.
    16. Notton T, Sardanyés J, Weinberger AD, Weinberger L. The case for transmissible antivirals to control population-wide infectious disease. Trends Biotechnol. 2014 Aug; 32(8):400-5. PMID: 25017994.
      View in: PubMed
    17. Dar RD, Hosmane NN, Arkin MR, Siliciano RF, Weinberger L. Screening for noise in gene expression identifies drug synergies. Science. 2014 Jun 20; 344(6190):1392-6. PMID: 24903562; PMCID: PMC4122234.
    18. Rouzine IM, Coffin JM, Weinberger L. 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.
    19. Fong EJ, Johnston AC, Notton T, Jung SY, Rose KA, Weinberger L, Shusteff M. Acoustic focusing with engineered node locations for high-performance microfluidic particle separation. Analyst. 2014 Mar 07; 139(5):1192-200. PMID: 24448925.
      View in: PubMed
    20. Weinberger AD, Weinberger L. Stochastic fate selection in HIV-infected patients. Cell. 2013 Oct 24; 155(3):497-9. PMID: 24243007.
      View in: PubMed
    21. Rouzine IM, Weinberger L. 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.
    22. Gardner TJ, Bolovan-Fritts C, Teng MW, Redmann V, Kraus TA, Sperling R, Moran T, Britt W, Weinberger L, 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.
    23. Teng MW, Bolovan-Fritts C, Dar RD, Womack A, Simpson ML, Shenk T, Weinberger L. An endogenous accelerator for viral gene expression confers a fitness advantage. Cell. 2012 Dec 21; 151(7):1569-80. PMID: 23260143; PMCID: PMC3552493.
    24. Rouzine IM, Weinberger L. Design requirements for interfering particles to maintain coadaptive stability with HIV-1. J Virol. 2013 Feb; 87(4):2081-93. PMID: 23221552; PMCID: PMC3571494.
    25. Razooky BS, Gutierrez E, Terry VH, Spina CA, Groisman A, Weinberger L. Microwell devices with finger-like channels for long-term imaging of HIV-1 expression kinetics in primary human lymphocytes. Lab Chip. 2012 Nov 07; 12(21):4305-12. PMID: 22976503; PMCID: PMC3589574.
    26. Dar RD, Razooky BS, Singh A, Trimeloni TV, McCollum JM, Cox CD, Simpson ML, Weinberger L. 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.
    27. 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 01; 12(3):452-62. PMID: 23255218; PMCID: PMC3587446.
    28. Singh A, Razooky BS, Dar RD, Weinberger L. Dynamics of protein noise can distinguish between alternate sources of gene-expression variability. Mol Syst Biol. 2012; 8:607. PMID: 22929617; PMCID: PMC3435505.
    29. Metzger VT, Lloyd-Smith JO, Weinberger L. Autonomous targeting of infectious superspreaders using engineered transmissible therapies. PLoS Comput Biol. 2011 Mar; 7(3):e1002015. PMID: 21483468; PMCID: PMC3060167.
    30. Franz K, Singh A, Weinberger L. Lentiviral vectors to study stochastic noise in gene expression. Methods Enzymol. 2011; 497:603-22. PMID: 21601105.
      View in: PubMed
    31. Razooky BS, Weinberger L. 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.
    32. Singh A, Razooky B, Cox CD, Simpson ML, Weinberger L. 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.
    33. Weinberger AD, Perelson AS, Ribeiro RM, Weinberger L. Accelerated immunodeficiency by anti-CCR5 treatment in HIV infection. PLoS Comput Biol. 2009 Aug; 5(8):e1000467. PMID: 19680436; PMCID: PMC2715863.
    34. Singh A, Weinberger L. Stochastic gene expression as a molecular switch for viral latency. Curr Opin Microbiol. 2009 Aug; 12(4):460-6. PMID: 19595626; PMCID: PMC2760832.
    35. Weinberger L, 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
    36. Weinberger L, Shenk T. An HIV feedback resistor: auto-regulatory circuit deactivator and noise buffer. PLoS Biol. 2007 Jan; 5(1):e9. PMID: 17194214; PMCID: PMC1717016.
    37. Weinberger L, 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
    38. Weinberger L, 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.
    39. 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