Abstract:

The ubiquitin system is a primary conduit for the regulated degradation of cellular proteins. Ubiquitination describes the covalent modification of protein substrates with ubiquitin, a small protein that binds the proteasome and directs substrate degradation. Our goal is to co-opt the ubiquitin system, and more broadly protein homeostasis, to irreversibly regulate challenging therapeutic targets for enhanced clinical efficacy. Our efforts are focused on targets for which there is a clear rationale for homeostatic regulation over target inhibition. We will discuss strategies to co-opt protein homeostasis, highlight mechanisms for how selective targeting can be achieved, and review the cellular and physiological consequences of target regulation, with an emphasis on maximizing safety and therapeutic benefit for patients.

Bio:

Ingrid E. Wertz is a co-founder and the CEO of Lyterian Therapeutics. She obtained her undergraduate degree in Molecular and Cellular Biology from the University of California at Berkeley, performed her graduate studies at Genentech via an NIH Biotechnology Training Grant from U.C. Davis, and received her M.D. from Washington University in St. Louis as a Medical Scientist Training Program fellow. Following her graduate work, Ingrid joined Genentech where she co-initiated and led the Genentech Degrader Platform and contributed to numerous drug discovery programs, including those leading to the discovery of venetoclax and giredistrant. Following Genentech, Ingrid was the Executive Director of the Protein Homeostasis Center of Excellence at Bristol Myers Squibb. Dr. Wertz’s research is primarily focused on strategies to identify and harness endogenous protein homeostasis machinery for therapeutic benefit.