Brad is using a structure-based approach to develop a pharmaceutical which can restore activity to mutant p53 proteins in cancer. The tumor suppressor p53 is an important cell-cycle regulating transcription factor that is mutated in 50% of human cancers. Most of these oncogenic p53 mutations create a single amino acid substitution in the DNA-binding domain (DBD), leading to continued expression of full-length but nonfunctional p53 protein. A pharmaceutical that can restore wild-type p53 function to these single amino acid mutants, could have an enormous impact on our ability to treat cancers with p53 mutations. We identified a novel class of small molecules which are able to stabilize the fold of mutant p53 proteins in vitro and induces mutant p53-dependent cell death in cancer cells. His objective is to understand the molecular mechanism that allows these small molecules to restore function to oncogenic p53 mutants, from atomic-level interactions with the p53 DBD to the induced changes in biochemical function of the p53 DBD.
Brad is a native of Texas, growing up in north Dallas and graduating from the University of Texas with a bachelor’s degree in Biology. He is currently in his fourth year of the Medical Scientist Training Program at UC Irvine.