Leor Weinberger, PhD

Director
Biochemistry And Biophysics
+1 415 734-4857

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. 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.

Publications: 

Disrupting autorepression circuitry generates ''open-loop lethality'' to yield escape-resistant antiviral agents.

Cell

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

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

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

Chaturvedi S, Beutler N, Pablo M, Vasen G, Chen X, Calia G, Buie L, Rodick R, Smith D, Rogers T, Weinberger LS

Disrupting autorepression circuitry generates "open-loop lethality" to yield escape-resistant antiviral agents.

Cell

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

Brahma safeguards canalization of cardiac mesoderm differentiation.

Nature

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, Kathiriya IS, Krogan NJ, Saucerman JJ, Bruneau BG

Identification of a therapeutic interfering particle-A single-dose SARS-CoV-2 antiviral intervention with a high barrier to resistance.

Cell

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 affect transcriptional noise to promote cell fate transitions.

Science (New York, N.Y.)

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

RanDeL-Seq: a High-Throughput Method to Map Viral cis- and trans-Acting Elements.

mBio

Notton T, Glazier JJ, Saykally VR, Thompson CE, 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

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

The HSV-1 ICP4 Transcriptional Auto-Repression Circuit Functions as a Transcriptional "Accelerator" Circuit.

Frontiers in cellular and infection microbiology

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

Li Y, Shan Y, Desai RV, Cox KH, Weinberger LS, Takahashi JS

HIV Latency: Stochastic across Multiple Scales.

Cell host & microbe

Hansen MMK, Martin B, Weinberger LS

Attacking Latent HIV with convertibleCAR-T Cells, a Highly Adaptable Killing Platform.

Cell

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

Hansen MMK, Weinberger LS

Feedback-mediated signal conversion promotes viral fitness.

Proceedings of the National Academy of Sciences of the United States of America

Vardi N, Chaturvedi S, Weinberger LS

A Post-Transcriptional Feedback Mechanism for Noise Suppression and Fate Stabilization.

Cell

Hansen MMK, Wen WY, Ingerman E, Razooky BS, Thompson CE, Dar RD, Chin CW, Simpson ML, Weinberger LS

A Bioreactor Method to Generate High-titer, Genetically Stable, Clinical-isolate Human Cytomegalovirus.

Bio-protocol

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

Razooky BS, Cao Y, Hansen MMK, Perelson AS, Simpson ML, Weinberger LS

Transcriptional Bursting Explains the Noise-Versus-Mean Relationship in mRNA and Protein Levels.

PloS one

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

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

Rast LI, Rouzine IM, Rozhnova G, Bishop L, Weinberger AD, Weinberger LS

Exploiting Genetic Interference for Antiviral Therapy.

PLoS genetics

Tanner EJ, Kirkegaard KA, Weinberger LS

A minimal fate-selection switch.

Current opinion in cell biology

Weinberger LS

The Low Noise Limit in Gene Expression.

PloS one

Dar RD, Razooky BS, Weinberger LS, Cox CD, Simpson ML

A hardwired HIV latency program.

Cell

Razooky BS, Pai A, Aull K, Rouzine IM, Weinberger LS

An evolutionary role for HIV latency in enhancing viral transmission.

Cell

Rouzine IM, Weinberger AD, Weinberger LS

Stochastic variability in HIV affects viral eradication.

Proceedings of the National Academy of Sciences of the United States of America

Rouzine IM, Razooky BS, Weinberger LS

The case for transmissible antivirals to control population-wide infectious disease.

Trends in biotechnology

Notton T, Sardanyés J, Weinberger AD, Weinberger LS

Screening for noise in gene expression identifies drug synergies.

Science (New York, N.Y.)

Dar RD, Hosmane NN, Arkin MR, Siliciano RF, Weinberger LS

Acoustic focusing with engineered node locations for high-performance microfluidic particle separation.

The Analyst

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

Roy D. Dar, Leor S. Weinberger

Structure and Function of a Transcriptional ‘Accelerator’ Circuit.

Biophysical journal

Roy Dar, Cynthia Bolovan-Fritts, Melissa Teng, Brian Linhares, Michael Simpson, Leor S. Weinberger

Stochastic fate selection in HIV-infected patients.

Cell

Weinberger AD, Weinberger LS

Development of a high-throughput assay to measure the neutralization capability of anti-cytomegalovirus antibodies.

Clinical and vaccine immunology : CVI

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

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

Igor M Rouzine, Leor S Weinberger

An endogenous accelerator for viral gene expression confers a fitness advantage.

Cell

Teng MW, Bolovan-Fritts C, Dar RD, Womack A, Simpson ML, Shenk T, 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

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

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.)

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

Singh A, Razooky BS, Dar RD, Weinberger LS

Autonomous targeting of infectious superspreaders using engineered transmissible therapies.

PLoS computational biology

Metzger VT, Lloyd-Smith JO, Weinberger LS

Lentiviral vectors to study stochastic noise in gene expression.

Methods in enzymology

Franz K, Singh A, Weinberger LS

Accelerated immunodeficiency by anti-CCR5 treatment in HIV infection.

PLoS computational biology

Weinberger AD, Perelson AS, Ribeiro RM, Weinberger LS

Stochastic gene expression as a molecular switch for viral latency.

Current opinion in microbiology

Singh A, Weinberger LS

Negative Feedback Speeds Transcriptional Response-Time In Human Cytomegalovirus.

Biophysical journal

Melissa L. Wong, Cynthia Bolovan-Fritts, Leor S. Weinberger

Transient-mediated fate determination in a transcriptional circuit of HIV.

Nature genetics

Weinberger LS, Dar RD, Simpson ML

Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy.

The Journal of experimental medicine

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

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

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

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