Abood Okal

Graduate Student

Department of Pharmaceutics & Pharmaceutical Chemistry

30 S 2000 E
LS Skaggs Pharmacy Institute
Salt Lake City, Utah, 84112
ph: 801.581.7120
email: abood.okal@utah.edu

 Research Project

The tumor suppressor p53, a 393 amino acid sequence-specific transcription factor, is encoded by the TP53 gene which is localized on chromosome 17 of the human genome. Half of all tumors have mutant p53, while inactivity of p53 defines the majority of the remaining cancer cases. This indeed indicates the importance of the apoptotic activity of p53 upon cellular stress.  p53 gene therapy may be the ultimate cure for many cancers, especially those that are resistance to current treatments. Thus, our research is mainly focused on developing new methods of restoring and enhancing p53 activity on different levels to cure cancer.

I am optimizing a p53 “protein switch” that exploits our emerging technology where ligand induction leads to nuclear accumulation of the target protein.  Nuclear localization is an essential requirement for p53 to induce the extrinsic and intrinsic apoptotic pathways.  Importantly, p53 in many cancers is found to be mislocalized to the cytoplasm. Another area of interest is to capture non-mutated mislocalized endogenous p53 present in inflammatory breast carcinoma (IBC), a particularly aggressive and deadly form of breast cancer, and translocate it to the nucleus using our protein switch technology. Finally, I am investigating the impact of certain mutations and alterations in p53 that may give rise to an enhanced and more active p53. Our ultimate goal is to utilize nuclear targeting, mitochondrial targeting, and enhanced p53, to eradicate breast cancer.