Leor Weinberger, PhD
Research Associate WOS
Pharmaceutical Chemistry
School of Pharmacy

Weinberger and colleagues discovered the HIV latency circuit (Weinberger* et al. Cell 2005), which provided the first experimental evidence that stochastic fluctuations (‘noise’) in gene expression drive biological fate decisions. Noise-driven decisions were then found in systems ranging from bacteria to cancer.

Show full bio (220 words) Hide full bio

The lab's studies overturned dogma in the field by showing that HIV latency was a ‘hardwired’ virus program (Razooky et al. Cell 2015; Rouzine et al. Cell 2015) and discovered stochastic latency programs in other viruses (Chaturvedi et al. PNAS 2020). For these contributions, Weinberger received the NIH Avant-Garde award for HIV research and an NIH Merit Award.

The lab discovered noise-enhancer molecules (Dar et al. Science 2014), now used by numerous other labs—e.g., to modulate circadian rhythms (Li et al. PNAS 2020)—and discovered a cellular noise-control pathway that potentiates embryonic cell-fate transitions (Desai et al. Science 2021). These studies demonstrated that transcriptional noise can be a ‘feature not a bug’ of cellular systems and play a functional, physiological role.

On the therapeutic front, the lab conceptualized and forwarded Therapeutic Interfering Particles (TIPs) (Weinberger et al. J Virol. 2003)—a first-in-class antiviral countermeasure that is single-dose and escape-resistant (see TED talk, below). The lab's initial work led to the DARPA INTERCEPT program (a $40M initiative that funded dozens of virology labs worldwide from 2015–20). In 2020, the lab discovered TIPs for SARS-CoV-2 (Chaturvedi et al. Cell 2021)—the first TIP reported for any virus—and provided long-sought evidence for the therapeutic effect of the TIP mechanism of action. Following FDA reviews, the DoD and NIH funded TIP clinical trials for HIV and SARS-CoV-2.

Awards

Show all (25) Hide

• Seattle Children's Research Innovator Award (Inaugural), 2022
• Oustanding Mentor award, Gladstone/UCSF, 2022
• NIH Director's Transformative Research Award (TRA), 2021
• NIH MERIT Award, 2021
• NIH Avant-Garde Award, 2020
• William and Ute Bowes Distinguished Professor, 2017
• Blavatnik Scholar, 2016
• American Institute for Mechanical and Biological Engineering (AIMBE), College of Fellows, 2015
• NIH Director's Pioneer Award, 2013
• NIH/NIDA Avant Garde Award for HIV Research (deferred), 2013
• Alfred P. Sloan Research Fellow, 2011
• Bill & Melinda Gates Foundation, Grand Challenges Award, 2009
• California HIV/AIDS Foundation, Young Investigator Innovative Development Award, 2009
• NIH Director's New Innovator Award, 2009
• W.M. Keck Foundation, Research Excellence Award, 2009
• NIH K25 Career Development Award, 2008
• Pew Scholar in the Biomedical Sciences, 2008
• Lewis Thomas Fellowship, Princeton University, 2004
• E. Cota-Robles Fellowship, UC Berkeley, 1999
• Howard Hughes Medical Institute (HHMI) Pre-Doctoral Fellowship, 1999
• HHMI Undergraduate Research Fellowship, 2nd Award, 1997
• John Prost Award, University of Maryland, 1997
• Maryland Distinguished Scholar, 1996
• HHMI Undergraduate Research Fellowship, 1995
• NIH FAES Fellow, 1993

Education & Training

Show all (3) Hide

• Lewis-Thomas Fellow Molecular Biology Princeton University 2007
• Ph.D. Biophysics University of California, Berkeley 2004
• B.Sc. Biology, Physics University of Maryland, College Park (Hons.) 1998

Interests

Show all (3) Hide

• synthetic biology
• virology
• expression noise

Websites

Show all (3) Hide

• Weinberger Lab (weinbergerlab.ucsf.edu)
• Gladstone (gladstone.org)
• TED Talk (ted.com)

Grants and Projects

Show all (10) Hide

• Stochastic Gene Expression in Retroviral Latency, NIH, 2014-2026
• A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups, NIH, 2020-2025
• Autonomously deploying, co-evolving SARS-CoV-2 antiviral: a new paradigm for pandemic prevention, NIH, 2021-2024
• Development of a Technology Platform for Engineering Single-Administration HIV Therapeutics, NIH, 2019-2021
• Evolvable 'Resistance-Proof' Therapies, NIH, 2013-2020
• Experiment & Theory to Test an Evolutionary Fitness Role for Lentiviral Latency, NIH, 2014-2016
• Martin Delaney Collaboratory to Eradicate HIV-1 Infection, NIH, 2011-2016
• Global innate immune responses to HIV-1 infection, NIH, 2010-2015
• Developing Transmissible Antivirals by Exploiting Gene-Expression Circuitry, NIH, 2009-2014
• How Feedback Circuitry Drives Phenotype Switching in a Human Herpesvirus, NIH, 2008-2013

Publications (72)

Top publication keywords:
HIV Long Terminal RepeatFeedback, Physiologicaltat Gene Products, Human Immunodeficiency VirusStochastic ProcessesHIV-1Gene Expression Regulation, ViralVirus ReplicationRNA, MessengerHIVAntiviral AgentsVirus LatencyDefective VirusesSingle Molecule ImagingCytomegalovirusTranscription, Genetic

• Disrupting autorepression circuitry generates "open-loop lethality" to yield escape-resistant antiviral agents.
  Cell 2022 Chaturvedi S, Pablo M, Wolf M, Rosas-Rivera D, Calia G, Kumar AJ, Vardi N, Du K, Glazier J, Ke R, Chan MF, Perelson AS, Weinberger LS
• Identification of a therapeutic interfering particle-A single-dose SARS-CoV-2 antiviral intervention with a high barrier to resistance.
  Cell 2021 Chaturvedi S, Vasen G, Pablo M, Chen X, Beutler N, Kumar A, Tanner E, Illouz S, Rahgoshay D, Burnett J, Holguin L, Chen PY, Ndjamen B, Ott M, Rodick R, Rogers T, Smith DM, Weinberger LS
• A DNA repair pathway can regulate transcriptional noise to promote cell fate transitions.
  Science (New York, N.Y.) 2021 Desai RV, Chen X, Martin B, Chaturvedi S, Hwang DW, Li W, Yu C, Ding S, Thomson M, Singer RH, Coleman RA, Hansen MMK, Weinberger LS
• A molecular mechanism for probabilistic bet hedging and its role in viral latency.
  Proceedings of the National Academy of Sciences of the United States of America 2020 Chaturvedi S, Klein J, Vardi N, Bolovan-Fritts C, Wolf M, Du K, Mlera L, Calvert M, Moorman NJ, Goodrum F, Huang B, Weinberger LS
• A Post-Transcriptional Feedback Mechanism for Noise Suppression and Fate Stabilization.
  Cell 2018 Hansen MMK, Wen WY, Ingerman E, Razooky BS, Thompson CE, Dar RD, Chin CW, Simpson ML, Weinberger LS
• A hardwired HIV latency program.
  Cell 2015 Razooky BS, Pai A, Aull K, Rouzine IM, Weinberger LS
• An evolutionary role for HIV latency in enhancing viral transmission.
  Cell 2015 Rouzine IM, Weinberger AD, Weinberger LS
• Screening for noise in gene expression identifies drug synergies.
  Science (New York, N.Y.) 2014 Dar RD, Hosmane NN, Arkin MR, Siliciano RF, Weinberger LS

Show all (64 more) Hide

• Single-cell RNA sequencing algorithms underestimate changes in transcriptional noise compared to single-molecule RNA imaging.
  Cell reports methods 2024 Khetan N, Zuckerman B, Calia GP, Chen X, Garcia Arceo X, Weinberger LS
• Quantitative comparison of single-cell RNA sequencing versus single-molecule RNA imaging for quantifying transcriptional noise.
  bioRxiv : the preprint server for biology 2024 Khetan N, Zuckerman B, Calia GP, Chen X, Arceo XG, Weinberger LS
• Engineered deletions of HIV replicate conditionally to reduce disease in nonhuman primates.
  Science (New York, N.Y.) 2024 Pitchai FNN, Tanner EJ, Khetan N, Vasen G, Levrel C, Kumar AJ, Pandey S, Ordonez T, Barnette P, Spencer D, Jung SY, Glazier J, Thompson C, Harvey-Vera A, Son HI, Son HI, Strathdee SA, Holguin L, Urak …
• Evidence for Behavioral Autorepression in Covid-19 Epidemiological Dynamics.
  medRxiv : the preprint server for health sciences 2024 Lewis DD, Pablo M, Chen X, Simpson ML, Weinberger L
• Expression of thioredoxin-1 in the ASJ neuron corresponds with and enhances intrinsic regenerative capacity under lesion conditioning in C. elegans.
  FEBS letters 2023 Grooms NWF, Fitzgerald MQ, Zuckerman B, Ureña SE, Weinberger LS, Chung SH
• Disrupting autorepression circuitry generates ''open-loop lethality'' to yield escape-resistant antiviral agents.
  Cell 2023 Chaturvedi S, Pablo M, Wolf M, Rosas-Rivera D, Calia G, Kumar AJ, Vardi N, Du K, Glazier J, Ke R, Chan MF, Perelson AS, Weinberger LS
• Comparative analysis between single-cell RNA-seq and single-molecule RNA FISH indicates that the pyrimidine nucleobase idoxuridine (IdU) globally amplifies transcriptional noise.
  bioRxiv : the preprint server for biology 2023 Calia GP, Chen X, Zuckerman B, Weinberger LS
• A single-administration therapeutic interfering particle reduces SARS-CoV-2 viral shedding and pathogenesis in hamsters.
  Proceedings of the National Academy of Sciences of the United States of America 2022 Chaturvedi S, Beutler N, Vasen G, Pablo M, Chen X, Calia G, Buie L, Rodick R, Smith D, Rogers T, Weinberger LS
• A single-administration therapeutic interfering particle reduces SARS-CoV-2 viral shedding and pathogenesis in hamsters.
  bioRxiv : the preprint server for biology 2022 Chaturvedi S, Beutler N, Pablo M, Vasen G, Chen X, Calia G, Buie L, Rodick R, Smith D, Rogers T, Weinberger LS
• A DNA repair pathway can regulate transcriptional noise to promote cell fate transitions.
  Biophysical Journal 2022 Leor S. Weinberger
• Brahma safeguards canalization of cardiac mesoderm differentiation.
  Nature 2022 Hota SK, Rao KS, Blair AP, Khalilimeybodi A, Hu KM, Thomas R, So K, Kameswaran V, Xu J, Polacco BJ, Desai RV, Chatterjee N, Hsu A, Muncie JM, Blotnick AM, Winchester SAB, Weinberger LS, Hüttenhain R, …
• Evaluation of Singer et al.: Technical points on analyzing viral replication kinetics in single cells.
  Cell systems 2021 Chen X, Pablo M, Weinberger L
• RanDeL-Seq: a High-Throughput Method to Map Viral cis- and trans-Acting Elements.
  mBio 2021 Notton T, Glazier JJ, Saykally VR, Thompson CE, Weinberger LS
• The HSV-1 ICP4 Transcriptional Auto-Repression Circuit Functions as a Transcriptional "Accelerator" Circuit.
  Frontiers in cellular and infection microbiology 2020 Chaturvedi S, Engel R, Weinberger L
• Noise-driven cellular heterogeneity in circadian periodicity.
  Proceedings of the National Academy of Sciences of the United States of America 2020 Li Y, Shan Y, Desai RV, Cox KH, Weinberger LS, Takahashi JS
• HIV Latency: Stochastic across Multiple Scales.
  Cell host & microbe 2019 Hansen MMK, Martin B, Weinberger LS
• Attacking Latent HIV with convertibleCAR-T Cells, a Highly Adaptable Killing Platform.
  Cell 2019 Herzig E, Kim KC, Packard TA, Vardi N, Schwarzer R, Gramatica A, Deeks SG, Williams SR, Landgraf K, Killeen N, Martin DW, Weinberger LS, Greene WC
• Post-Transcriptional Noise Control.
  BioEssays : news and reviews in molecular, cellular and developmental biology 2019 Hansen MMK, Weinberger LS
• Cytoplasmic Amplification of Transcriptional Noise Generates Substantial Cell-to-Cell Variability.
  Cell systems 2018 Hansen MMK, Desai RV, Simpson ML, Weinberger LS
• Feedback-mediated signal conversion promotes viral fitness.
  Proceedings of the National Academy of Sciences of the United States of America 2018 Vardi N, Chaturvedi S, Weinberger LS
• A Bioreactor Method to Generate High-titer, Genetically Stable, Clinical-isolate Human Cytomegalovirus.
  Bio-protocol 2017 Saykally VR, Rast LI, Sasaki J, Jung SY, Bolovan-Fritts C, Weinberger LS
• Nonlatching positive feedback enables robust bimodality by decoupling expression noise from the mean.
  PLoS biology 2017 Razooky BS, Cao Y, Hansen MMK, Perelson AS, Simpson ML, Weinberger LS
• Fate-Regulating Circuits in Viruses: From Discovery to New Therapy Targets.
  Annual review of virology 2017 Pai A, Weinberger LS
• Transient Thresholding: A Mechanism Enabling Noncooperative Transcriptional Circuitry to Form a Switch.
  Biophysical journal 2017 Aull KH, Tanner EJ, Thomson M, Weinberger LS
• Transcriptional Bursting Explains the Noise-Versus-Mean Relationship in mRNA and Protein Levels.
  PloS one 2016 Dar RD, Shaffer SM, Singh A, Razooky BS, Simpson ML, Raj A, Weinberger LS
• The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7.
  The Journal of biological chemistry 2016 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
• Conflicting Selection Pressures Will Constrain Viral Escape from Interfering Particles: Principles for Designing Resistance-Proof Antivirals.
  PLoS computational biology 2016 Rast LI, Rouzine IM, Rozhnova G, Bishop L, Weinberger AD, Weinberger LS
• Exploiting Genetic Interference for Antiviral Therapy.
  PLoS genetics 2016 Tanner EJ, Kirkegaard KA, Weinberger LS
• A minimal fate-selection switch.
  Current opinion in cell biology 2015 Weinberger LS
• The Low Noise Limit in Gene Expression.
  PloS one 2015 Dar RD, Razooky BS, Weinberger LS, Cox CD, Simpson ML
• Spatial tuning of acoustofluidic pressure nodes by altering net sonic velocity enables high-throughput, efficient cell sorting.
  Lab on a chip 2015 Jung SY, Notton T, Fong E, Shusteff M, Weinberger LS
• Stochastic variability in HIV affects viral eradication.
  Proceedings of the National Academy of Sciences of the United States of America 2014 Rouzine IM, Razooky BS, Weinberger LS
• The case for transmissible antivirals to control population-wide infectious disease.
  Trends in biotechnology 2014 Notton T, Sardanyés J, Weinberger AD, Weinberger LS
• Fifteen years later: hard and soft selection sweeps confirm a large population number for HIV in vivo.
  PLoS genetics 2014 Rouzine IM, Coffin JM, Weinberger LS
• Acoustic focusing with engineered node locations for high-performance microfluidic particle separation.
  The Analyst 2014 Fong EJ, Johnston AC, Notton T, Jung SY, Rose KA, Weinberger LS, Shusteff M
• Altering Stochastic Noise in Gene Expression for HIV Therapy.
  Biophysical Journal 2014 Roy D. Dar, Leor S. Weinberger
• Structure and Function of a Transcriptional ‘Accelerator’ Circuit.
  Biophysical Journal 2014 Roy Dar, Cynthia Bolovan-Fritts, Melissa Teng, Brian Linhares, Michael Simpson, Leor S. Weinberger
• Stochastic fate selection in HIV-infected patients.
  Cell 2013 Weinberger AD, Weinberger LS
• Reply to "Coadaptive stability of interfering particles with HIV-1 when there is an evolutionary conflict".
  Journal of virology 2013 Rouzine IM, Weinberger LS
• Development of a high-throughput assay to measure the neutralization capability of anti-cytomegalovirus antibodies.
  Clinical and vaccine immunology : CVI 2013 Gardner TJ, Bolovan-Fritts C, Teng MW, Redmann V, Kraus TA, Sperling R, Moran T, Britt W, Weinberger LS, Tortorella D
• An Endogenous Accelerator for Viral Gene Expression Confers a Fitness Advantage.
  Cell 2013 Melissa W. Teng, Cynthia Bolovan-Fritts, Roy D. Dar, Andrew Womack, Michael L. Simpson, Thomas Shenk, Leor S. Weinberger
• The quantitative theory of within-host viral evolution.
  Journal of Statistical Mechanics Theory and Experiment 2013 Igor M Rouzine, Leor S Weinberger
• An endogenous accelerator for viral gene expression confers a fitness advantage.
  Cell 2012 Teng MW, Bolovan-Fritts C, Dar RD, Womack A, Simpson ML, Shenk T, Weinberger LS
• Design requirements for interfering particles to maintain coadaptive stability with HIV-1.
  Journal of virology 2012 Rouzine IM, Weinberger LS
• Microwell devices with finger-like channels for long-term imaging of HIV-1 expression kinetics in primary human lymphocytes.
  Lab on a chip 2012 Razooky BS, Gutierrez E, Terry VH, Spina CA, Groisman A, Weinberger LS
• Transcriptional burst frequency and burst size are equally modulated across the human genome.
  Proceedings of the National Academy of Sciences of the United States of America 2012 Dar RD, Razooky BS, Singh A, Trimeloni TV, McCollum JM, Cox CD, Simpson ML, Weinberger LS
• BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism.
  Cell cycle (Georgetown, Tex.) 2012 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
• Dynamics of protein noise can distinguish between alternate sources of gene-expression variability.
  Molecular systems biology 2012 Singh A, Razooky BS, Dar RD, Weinberger LS
• Autonomous targeting of infectious superspreaders using engineered transmissible therapies.
  PLoS computational biology 2011 Metzger VT, Lloyd-Smith JO, Weinberger LS
• Lentiviral vectors to study stochastic noise in gene expression.
  Methods in enzymology 2011 Franz K, Singh A, Weinberger LS
• Mapping the architecture of the HIV-1 Tat circuit: A decision-making circuit that lacks bistability and exploits stochastic noise.
  Methods (San Diego, Calif.) 2010 Razooky BS, Weinberger LS
• Transcriptional bursting from the HIV-1 promoter is a significant source of stochastic noise in HIV-1 gene expression.
  Biophysical journal 2010 Singh A, Razooky B, Cox CD, Simpson ML, Weinberger LS
• Accelerated immunodeficiency by anti-CCR5 treatment in HIV infection.
  PLoS computational biology 2009 Weinberger AD, Perelson AS, Ribeiro RM, Weinberger LS
• Stochastic gene expression as a molecular switch for viral latency.
  Current opinion in microbiology 2009 Singh A, Weinberger LS
• Negative Feedback Speeds Transcriptional Response-Time In Human Cytomegalovirus.
  Biophysical Journal 2009 Melissa L. Wong, Cynthia Bolovan-Fritts, Leor S. Weinberger
• Transient-mediated fate determination in a transcriptional circuit of HIV.
  Nature genetics 2008 Weinberger LS, Dar RD, Simpson ML
• An HIV feedback resistor: auto-regulatory circuit deactivator and noise buffer.
  PLoS biology 2007 Weinberger LS, Shenk T
• Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity.
  Cell 2005 Weinberger LS, Burnett JC, Toettcher JE, Arkin AP, Schaffer DV
• Theoretical design of a gene therapy to prevent AIDS but not human immunodeficiency virus type 1 infection.
  Journal of virology 2003 Weinberger LS, Schaffer DV, Arkin AP
• Early hepatitis C viral kinetics correlate with long-term outcome in patients receiving high dose induction followed by combination interferon and ribavirin therapy.
  Journal of hepatology 2002 Rosen HR, Ribeiro RR, Weinberger L, Wolf S, Chung M, Gretch DR, Perelson AS
• Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy.
  The Journal of experimental medicine 2001 Mohri H, Perelson AS, Tung K, Ribeiro RM, Ramratnam B, Markowitz M, Kost R, Hurley A, Weinberger L, Cesar D, Hellerstein MK, Ho DD
• Different turnover rate of hepatitis C virus clearance by different treatment regimen using interferon-beta.
  Journal of hepatology 2000 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
• Rapid turnover rate of hepatitis C virus clearance by the twice-a-day treatment regimen using interferon-beta.
  Gastroenterology 2000 Yasushi Shiratori, As Perelson, L. Weinberger, F. Imazeki, O. Yokosuka, R. Nakata, M. Omata
• Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques.
  The Journal of experimental medicine 1999 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