Leor S. Weinberger, PhD

Associate Investigator

Phone: (415) 734-4857
Fax: (415) 355-0855
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Other Professional Titles

Associate Professor, Biochemistry & Biophysics, University of California, San Francisco

Administrative Assistant

Kim Osborn
(415) 734-4857
kim.osborn@gladstone.ucsf.edu

More about Dr. Weinberger

Dr. Weinberger’s primary research focuses on fundamental principles of gene regulation, and, more specifically, on the regulatory "master circuits" that control HIV and human herpes viruses. His laboratory employs a coupled, computational-experimental approach that relies on quantitative, time-lapse fluorescence microscopy with mathematical modeling to study viral gene-expression circuits and expression "noise" at the single-cell level.

Before joining the Gladstone Institute of Virology and Immunology and UCSF in 2011, Dr. Weinberger was an Assistant Professor of Chemistry and Biochemistry at the University of California, San Diego.

He has been named an Alfred P. Sloan Foundation Research Fellow and has won the W.M. Keck Foundation Research Excellence Award, the California HIV/AIDS Young Investigator Innovative Development Award, the Bill and Melinda Gates Grand Challenges Award, the NIH Director’s New Innovator Award, the NIH Avant-Garde Award (declined), and the NIH Director's Pioneer Award.  He is the only individual ever to win the NIH Director's Pioneer, Avant-Garde, and New Innovator awards.  Dr. Weinberger is a member of numerous scientific societies, was a Visiting Professor at Harvard Medical School, and serves on the Innovation Review Panel for the Bill and Melinda Gates Foundation.


Dr. Weinberger earned a bachelor’s degree in 1998 at the University of Maryland, College Park, where he studied physics and biology. He then spent a year at the Los Alamos National Laboratory as a Department of Energy Scholar in the Theoretical Biophysics and Biology Group. In 2004, he earned a PhD in biophysics from the University of California, Berkeley, where he was a Howard Hughes Medical Institute Predoctoral Fellow. Dr. Weinberger then received postdoctoral training at Princeton University as a Lewis Thomas Fellow, working with Drs. Thomas Shenk and David Botstein.

 

More scientific details, please

Other Professional Titles

Associate Professor, Biochemistry & Biophysics, University of California, San Francisco

Administrative Assistant

Kim Osborn
(415) 734-4857
kim.osborn@gladstone.ucsf.edu

Areas of Investigation

Our laboratory is developing strategies to manipulate pathogen lifecycles by obtaining a detailed understanding of their regulatory mechanisms. To this end, we are defining the fundamental molecular mechanisms and regulatory principles that underlie how viruses (and cells in general) "decide" between alternate fates such as replicative versus dormant states.  We couple quantitative single-cell imaging approaches with computational and mathematical models to define the architecture, kinetics, and function of regulatory circuits that modulate cell fate.

A long-standing interest of the lab is to understand how HIV enters a long-lived dormant state termed proviral latency, which is a major barrier to eradicating the virus from infected individuals. We have defined how molecular fluctuations (also known as stochastic "noise") in gene expression of HIV Tat, influence proviral latency. This molecular "noise" is an unavoidable aspect of life at the single-cell level and arises from random thermal fluctuations in the concentration of molecules (proteins, mRNAs, etc.) within the cell. We have shown that by manipulating the regulatory circuitry that controls HIV noise, we can alter the ability of HIV to enter proviral latency.

Our ultimate goal is to develop novel therapies based on the newfound knowledge we gain. One exciting example of this is our recent effort to engineer transmissible antivirals to treat HIV  in resource-poor settings such as sub-Saharan Africa. Our models show that these transmissible therapies would be single-administration, could resist HIV mutation, could overcome behavioral barriers to disease control, and would automatically end up treating the highest-risk individuals.

Current Lab Focus

  • What are the fundamental molecular mechanisms that allow a single cell to choose between different developmental outcomes?
  • How does stochastic noise influence cell-fate decisions?
  • What principles govern viral gene-circuit behavior and influence cellular bifurcation into replication or latency of viruses?
  • Can we engineer novel therapies that transmit and co-evolve with replicating viruses?

Joined Gladstone

2011

Why Gladstone?

I came to Gladstone because of the exceptionally talented colleagues in HIV research.  In my mind, Gladstone is a world leader in HIV molecular biology research because it encourages its scientists to take bold risks for the betterment of human health.

Key Achievements

  • Proposed novel transmissible therapies (based on interfering particles) to reach hard-to-treat "high-risk" groups most in need of therapy; demonstrated that these transmissible therapies could overcome the major barriers to universal HIV control.
  • First demonstration that a gene-regulatory network harnesses noise in gene expression to control a cell-fate decision.
  • Identification of transcriptional ‘bursting’ as the molecular source of noise in HIV-1.
  • Succeeded in biasing HIV-1 toward latency by over-expressing cellular SirT1.

Education

University of Maryland, College Park (BSc), Biology and Physics, High Honors (1998)
University of California, Berkeley (PhD), Biophysics (2004)

Affiliations

Society for Mathematical Biology
Biophysical Society
American Society for Microbiology

Awards

  • Pioneer Award, National Institutes of Health (2013)
  • Alfred P. Sloan Foundation Research Fellow (2011)
  • NIH Director’s New Innovator Award (2009)
  • W.M. Keck Foundation Research Excellence Award (2009)
  • Bill & Melinda Gates Foundation, Grand Challenges Explorations Award (2009)
  • California HIV/AIDS Innovative Development Award (2009)
  • Pew Scholar in the Biomedical Sciences (2008)
  • NIH K25 Career Development Award (2008)
  • Princeton University Early Promotion, Research Associate → Research Staff (2006)
  • Princeton Dept of Molecular Biology Best Poster Award (2006)
  • Lewis Thomas Fellowship, Princeton University (2006)
  • External Thesis Reviewer, Dept. of Applied Maths, Witz University, South Africa (2006)
  • Berkeley Microscopy Award, Univ. of California, Berkeley (2003)
  • Howard Hughes Medical Institute Pre-doctoral Fellowship (1999)
  • DOE (URS) Research Scholarship, Los Alamos National Lab (1998)
  • Kupcinet Int’l Science Research Scholarship, Weizmann Institute of Science, Israel (1998)
  • NSF (REU) Research Scholarship, Univ. of California, San Diego (1997)
  • Phi Beta Kappa (1997)
  • University Honors Best Paper Award, Univ. of Maryland, Honors Program (1997)
  • Howard Hughes Medical Institute Undergraduate Research Scholar, Univ. of Maryland (1996)
  • Maryland Distinguished Scholar (1996)
  • University Honors Research Grant, Univ. of Maryland (1996)
  • John Prost Scholarly Writing Award, Univ of Maryland, Honors Program (1996)
  • FAES Fellow, National Institutes of Health (1993)
Syndicate publications

Featured Publications

Leor S. Weinberger, PhDMetzger VT, Lloyd-Smith JO, Weinberger LS. Autonomous targeting of infectious superspreaders using engineered transmissible therapies. PLoS Comput Biol. 2011 Mar; 7(3):e1002015. View in: PubMed
Leor S. Weinberger, PhDFranz K, Singh A, Weinberger LS. Lentiviral vectors to study stochastic noise in gene expression. Methods Enzymol. 2011; 497:603-22. View in: PubMed