Mechanisms of function and targeting for complexes relevant to cancer biology

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The long-term goals of this project are to help discover and interrogate new therapeutic targets for cancer. Current efforts are focused on structural features that might influence immunotherapy and novel interactions involving established anti-cancer targets. In collaboration with Dr. Naomi Taylor and Dr. Philippe Youkharibache, we are characterizing the structural and biophysical properties of CAR constructs, focusing on their folding, stability, oligomerization, and dynamics as well as the specificity and potency of target binding through an iterative process of i) structural and biophysical characterization of CAR modules, and ii) a systematic exploration of the sequence/structure/function relationships of CARs, with each guiding the other. We seek to develop a rationally designed approach for the optimization of CAR sequence-structure-function by contributing our structural and biophysical expertise to the effort of Dr. Taylor, a world-renowned immunologist with expertise in CAR-T applications for cancer treatment, and Dr. Youkharibache, an expert in computational structural modeling and simulation of CAR structure-dynamic behavior. We also collaborate with Dr. Doug Lowy, contributing our structural biology expertise to his long-standing efforts in analyzing cancer-associated Ras and Rho mutants.