Roy Dar to give November 10 Frontiers Lecture

Roy DarRoy Dar, Assistant Professor of Bioengineering, will lecture on “Modulating Gene Expression Fluctuations to Bias HIV Decision-Making and Stem Cell Fate Determination.” Jennifer Walters, MBM trainee and PhD student in Neuroscience, will give an introduction.

The lecture is free and open to the public at 4:00pm November 10, 2021 in 2269 Beckman Institute. A Zoom option will be available; join information is listed below.

Zoom Video Recording

Abstract:

Stochastic fluctuations are inherent to gene expression and can drive cell-fate specification. We exploit such fluctuations to control reactivation of human immunodeficiency virus (HIV) from latency—a quiescent state that is a major barrier to cure HIV. Using high-throughput single-cell screening, we have identified compounds that modulate HIV gene–expression fluctuations (i.e., “noise”), without changing mean expression.

These noise-modulating compounds would be neglected in conventional screens, and yet, they synergize or suppress the activity of potent activators in both Jurkat and primary cell models of viral latency. Therapies that reactivate and clear the latent reservoir are only partially effective, while latency promoting agents (LPAs) used to suppress reactivation and stabilize latency are under-studied and lack diversity in their mechanisms of action. The LPAs discovered in our noise drug screen stabilize latency and reduce latent reactivation when challenged by synergistic and potent combinations of HIV activators. These LPAs may provide new strategies to complement antiretroviral treatments.

Finally, I will discuss our recent efforts to control pluripotent gene expression noise in mouse embryonic stem cells (mESCs) with cell cycle arresting treatments. Understanding biochemical control of cell cycle and pluripotent gene expression noise can provide a foundation for designing mESC co-differentiation and multiple lineage commitment. Screening and assaying the modulation of gene expression noise presents an unexplored axis for drug discovery to control diseases and diverse cell-fate decisions.

Bio:

Roy Dar is an Assistant Professor of Bioengineering at the University of Illinois at Urbana-Champaign. He is affiliated with the Carl R. Woese Institute for Genomic Biology, Cancer Center at Illinois, Electrical and Computer Engineering Department, and the Center for Biophysics and Quantitative Biology.

He received a BSc in Physics and Mathematics at the Hebrew University of Jerusalem in Israel in 2004 and a PhD in Biophysics from the University of Tennessee, Knoxville in 2011 where he performed his research at Oak Ridge National Laboratory. He later trained as an NIH Ruth Kirschstein postdoctoral fellow at the Gladstone Institutes for Virology and Immunology at the University of California, San Francisco where he studied the exogenous drug control of HIV decision-making in single cells.

At the University of Illinois, he has received the NSF CAREER and NIH Trailblazer Awards for Early Stage Investigators. His lab aims to understand the fundamentals and applications of modulating fluctuations of gene expression in mammalian cells. His lab works on biasing HIV decision-making and stem cell fate determination at the single-cell level, genome-wide problems in systems biology, and viral-host relationships.

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