Research Projects

The level of protein tyrosine phosphorylation inside the cells is maintained by the concerted action of protein tyrosine phosphatases (PTPs) and protein tyrosine kinases (PTKs) that determine the outcome of the cellular function. Compared to the well-studies PTKs, the mechanistic details of PTPs function are still emerging. SHP2 is a PTP and is the first identified oncogene that play critical roles in two key cellular processes, the misfunction of which results in cancer and autoimmune diseases like diabetes. Hence, understanding the mechanistic details of SHP2 function could pave way for the treatment of diabetes and cancer. In this proposal, we seek to characterize the molecular basis for the SHP2 function by studying how the SHP2 regulates the interaction and hence, the activity of multiple phospho-tyrosine containing substrates that include IRS-1 and PD-1 using the combination of integrative structural biology techniques like X-ray crystallography and solution NMR spectroscopy along with other biophysical and biochemical techniques. The outcome of the proposal will aid in the development of small-molecule inhibitors based on the structure for the treatment of cancer and auto immune diseases like diabetes.