Leor Weinberger, PhD
Senior Investigator, Gladstone Institute for Virology and Immunology; Director, Gladstone Center for Cell Circuitry

Other Professional Titles

William & Ute Bowes Distinguished Professor
Professor of Pharmaceutical Chemistry, Biochemistry & Biophysics, University of California, San Francisco

Phone

(415) 734-4857

Fax

(415) 355-0855

Assistant

Julie Piper

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.

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?

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 demonstrated that a gene-regulatory network harnesses noise in gene expression to control a cell-fate decision.
Identified transcriptional ‘bursting’ as the molecular source of noise in HIV-1.
Successfully biased HIV-1 toward latency by over-expressing cellular SirT1.

Affiliations

  • Society for Mathematical Biology
  • Biophysical Society
  • American Society for Microbiology

Professional titles

William & Ute Bowes Distinguished Professor
Professor of Pharmaceutical Chemistry, Biochemistry & Biophysics, University of California, San Francisco

Education

1998
BS
  • Physics
  • Biology
  • University of Maryland, College Park
2004
PhD
  • Biophysics
  • University of California, Berkeley
2007
  • Gene Regulation
  • Lewis Thomas Fellow
  • Princeton University

Honors and Awards

2016 Blavatnik Scholar
2015 Elected Fellow, American Institute of Medical and Biomedical Engineers
2013 Pioneer Award, National Institutes of Health
2011 Alfred P. Sloan Foundation Research Fellow
2009 NIH Director’s New Innovator Award
2009 W.M. Keck Foundation Research Excellence Award
2009 Bill and Melinda Gates Foundation, Grand Challenges Explorations Award
2009 California HIV/AIDS Innovative Development Award
2008 Pew Scholar in the Biomedical Sciences
2008 NIH K25 Career Development Award
2006 Princeton University Early Promotion (Research Associate to Research Staff)
2006 Princeton Department of Molecular Biology Best Poster Award
2006 Lewis Thomas Fellowship, Princeton University
2006 External Thesis Reviewer, Depatment of Applied Maths, Witz University, South Africa
2003 Berkeley Microscopy Award, University of California, Berkeley
1999 Howard Hughes Medical Institute Pre-doctoral Fellowship
1998 DOE (URS) Research Scholarship, Los Alamos National Lab
1998 Kupcinet International Science Research Scholarship, Weizmann Institute of Science, Israel
1997 NSF (REU) Research Scholarship, University of California, San Diego
1997 Phi Beta Kappa
1997 University Honors Best Paper Award, University of Maryland, Honors Program
1996 Howard Hughes Medical Institute Undergraduate Research Scholar, University of Maryland
1996 Maryland Distinguished Scholar
1996 University Honors Research Grant, University of Maryland
1996 John Prost Scholarly Writing Award, University of Maryland, Honors Program
1993 FAES Fellow, National Institutes of Health