Leor Weinberger, PhD

Director, Gladstone Center for Cell Circuitry
William and Ute Bowes Distinguished Professor
Professor
Department of Biochemistry and Biophysics
Department of Pharmaceutical Chemistry
+1 415 734-4857
Research Description: 

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.

Primary Thematic Area: 
Virology & Microbial Pathogenesis
Secondary Thematic Area: 
Cancer Biology & Cell Signaling
Research Summary: 
Regulatory Circuitry of Viruses and Engineering Novel Therapeutics

Websites

Publications: 

HIV Latency: Stochastic across Multiple Scales.

Cell host & microbe

Hansen MMK, Martin B, Weinberger LS

HIV Latency: Stochastic across Multiple Scales.

Cell host & microbe

Maike M.K. Hansen, Benjamin Martin, Leor S. Weinberger

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