This latest funding will continue to support the research efforts of the Nyarko Lab
Our lab is interested in a variety of research questions aimed at understanding how WW domain proteins are regulated. This class of proteins, characterized by the presence of two signature tryptophan (W) residues, are implicated in several human diseases including cancer, chronic kidney diseases, Huntington’s, muscular dystrophy, and Alzheimer's. Because of their prominent role in human diseases most WW domain proteins are druggable targets and understanding the structural basis of their regulation is a key part of the drug design process and a major focus of the lab. Current research projects are focused on three WW domain proteins: - KIBRA, a kidney and brain protein associated with memory performance and chronic kidney diseases, and Yes-associated protein (YAP) and its Drosophila ortholog Yorkie, which promote cell growth and are over-expressed in several cancers. The interactions between the WW domains and multiple proline-rich motifs present in their predominantly disordered binding partners (IDPs) play important roles in their biological functions. We are particularly interested in understanding the factors that influence binding to their multivalent IDP partners and how these factors can be modulated to regulate the functions of the proteins. We combine molecular biology approaches withisothermal titration calorimetry, solution NMR (a state-of-the art Bruker 800 MHz Avance III instrument equipped with a TCI cryoprobe), and other biophysical techniques to address our experimental questions. Our long term goal is to use our findings to help direct the design of novel therapeutic strategies to stop or even reverse WW domain-related diseases.