Mapping genome-phenome relationships in large protein families
The Kannan lab is focused on pursuing biological questions connecting protein sequence, structure, function, and regulation as an essential step toward inferring causal genome-phenome relationships. We focus on large gene families such as protein kinases, glycosyltransferases, and ion channels that contribute to diverse disease phenotypes such as cancer, diabetes, Alzheimer’s, and Parkinson's'. We deploy systems approaches combining computational and experimental techniques to generate and test models of protein structure, function, evolution, and dynamics. We aim to develop personalized therapeutic strategies based on a deeper understanding of how these proteins work in disease and normal states. Our studies have provided new mechanistic insights into the unique modes of regulation in various protein kinases [1, 2], small molecule kinases [3], and pseudokinases [4] and have revealed the mechanism of action of oncogenic mutations in receptor tyrosine kinases [5]. We have also successfully employed the specialized tools and approaches developed for studying protein kinases to glycosyltransferases [6, 7] and are currently extending these approaches to studying ion channels.