Pradnya Narkhede
The eukaryotic translation elongation factor 1A (eEF1A) is an essential protein involved in protein translation, a fundamental process that is dysregulated in cancers and other pathologies. eEF1A is subject to extensive, dynamic chemical modification by a number of different enzymes, including those that methylate specific positions within the protein; by modulating eEF1A's activity during translation, these methylation events could alter the output of cellular protein synthesis, thus representing a new layer of gene-expression regulation in human health and disease. As such, I will integrate mechanistic biology, cancer physiology, and the development of quantitative proteomic tools to precisely characterize how the chemical modification state of eEF1A influences protein translation and cellular phenotypes in clinically-relevant systems. The results will shed light on the mechanisms underlying the pathogenesis of recalcitrant diseases, such as aggressive lung and pancreatic cancers, and inform new therapeutic modalities for these diseases.