Dr. Vadim Gaponenkos is an Associate Professor at the College of Medicine in the Department of Biochemistry and Molecular Genetics. His lab focuses on understanding how GTPase K-Ras, frequently mutated in cancer, can be inhibited with high potency and selectivity. His group found that G12V K-Ras-GDP can adapt an active-like conformation that allows it to interact with the calcium modulator protein calmodulin with high affinity. This feature appears to be unique to the G12V mutant and does not occur in wild type or G12D K-Ras-GDP. G12V K-Ras is found predominantly in highly aggressive and chemotherapy-resistant pancreatic and colorectal cancer. Detailed structural investigation of the novel mechanism of activation of K-Ras specific to its G12V oncogenic mutant has the potential to provide critical information for development of K-Ras inhibitors as anticancer therapeutics. The research in the Gaponenko lab is funded by an R01 grant from the National Cancer Institute. Dr. Gaponenkos lab uses Nuclear Magnetic Resonance (NMR) as a primary technique of structural analysis. Dr. Gaponenko received extensive training in NMR from the University of Cincinnati and from the National Cancer Institute. To complement the NMR studies, Dr. Gaponenko has developed a collaboration with Dr. Jeffery, an expert in X-ray crystallography, bringing novel contributions to his lab.
His research is focused on protein molecule function and macromolecular interactions.