Shams Reaz

Graduate Student

Department of Pharmaceutics & Pharmaceutical Chemistry

421 Wakara Way, Rm 306
Salt Lake City
Utah, 84108
USA
ph: 801.581.7120

Research Project

The tumor suppressor gene p53 plays a key role in tumor biology. In most cancer cells, p53 is found to be mutated or mislocalized, impotent to induce apoptosis and cell cycle arrest.  The nuclear accumulation of p53 is essential for its transcriptional activities to induce apoptosis. Therefore, one of the important research fields of modern cancer biology is developing therapeutics for restoration of p53 in cancer cells. In addition to restoration, several noble approaches have been made to improvise the structure of p53 for enhanced apoptotic function in both intrinsic and extrinsic pathways.

Binding of p53 to its target genes is the critical step for pro-apoptotic gene expression. Profound structural analysis of p53 and target DNA can reveal interaction between them and their surroundings. My current research project is to scrutinize the p53 DNA-binding domain and rationally design modified p53 by substituting with most favorable residues to achieve higher transcriptional and apoptotic activity. Concurrently, I am exploring MDM2 binding domain, responsible for the degradation of p53. My interest lies on the effect of either mutation or partial deletion of MBD on p53 potency without intruding its apoptotic function. Finally, our research goal is to design improvised p53 with enhanced apoptotic function and efficient delivery, targeting both mitochondria and nucleus simultaneously.