CCBIO seminar: Aaron S. Meyer
Engineering more precise and potent TAM-targeted therapies
Aaron S. Meyer
Department of Bioengineering, Jonsson Comprehensive Cancer Center, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA
TAM (Tyro3, AXL, MerTK) receptor tyrosine kinases (TAMRs) are critical regulators of immune response and tissue homeostasis. Immunological dysregulation of the family contributes to a wide range of diseases including cancer. TAMR activation in cancer cells serves as a mechanism of resistance to chemotherapies and targeted inhibitors. Further improving our understanding of the molecular events that lead to oncogenic TAMR function will enable rational design of more specific inhibitors with precise effects in vivo and help to identify the patients who will benefit from these therapies. In this talk, I will describe our efforts to identify the molecular events leading to TAMR activation, and how these events are tied to the receptors' physiological function. Using kinetic models of receptor activation, tied to inference techniques that rigorously consider model uncertainty, have helped us to identify new ways of rationally targeting the TAMR family. Using these tools, we are deconvolving the pleiotropic role these receptors play in tumor cell heterogeneity, metastasis, and immune suppression using combinations of these targeted treatments with data-driven modeling.
Chairperson: James B. Lorens, CCBIO