Allostery is a fundamental biochemical process in which one site on a protein influences the function of a different site on the same protein, even if they are far apart. Given this relationship, allosteric sites are versatile drug targets as they can activate, inhibit, or even provide a new function to the protein depending on the specific ligand. Yet, therapeutic cooption of allosteric sites remains limited, in part, due to the prevalence of invisible, cryptic allosteric sites that only appear upon ligand binding.

Dr. Divya Bezwada aims to transform our understanding of cryptic allosteric sites in Dr. Benjamin Cravatt’s lab at The Scripps Research Institute. There Dr. Bezwada will use a chemoproteomic approach to investigate the prevalence of cryptic allosteric sites across protein paralogs. Bezwada’s research will provide first principles regarding the evolution of cryptic allosteric sites and develop novel chemical tools with broad relevance for biological understanding and therapeutic applications.

Bezwada provided novel insight into cancer metabolism during her doctoral research in Dr. Ralph DeBerardinis’ lab at UT Southwestern Medical Center. There she found that clear cell renal cell carcinomas (ccRCC) have defects in the electron transport chain which suppresses oxidative phosphorylation. This result is consistent with decades of research into cancer metabolism. Unexpectedly, Bezwada found that ccRCC metastases upregulate oxidative phosphorylation and that this change is functionally important for metastasis. Bezwada’s discovery has crucial and paradigm-shifting implications for cancer patient treatment. Now, Bezwada will leverage chemical biology techniques to make her next important insights into human biology and disease during her postdoctoral research.