Rian Davis

Doctor of Pharmacy (Pharm.D)
Graduate Student

Department of Pharmaceutics & Pharmaceutical Chemistry

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

ph: 801.581.7120

Research Project

Protein expression and localization is paramount to proper function, and the aberration from either can lead to disease, such as cancer. My project is to develop a novel scientific approach to induce the degradation of these aberrant disease-causing proteins. Therapies have been designed to prevent protein expression, such as RNA interference, but a method to specifically induce the degradation of fully formed and functional intracellular proteins has not been established. This work aims to develop a system whereby a protein of interest can be selectively degraded. The concept has a three-step mechanism: 1) a new protein capable of controlled degradation is introduced into a cell, 2) this protein binds to the aberrant disease-causing protein, and 3) the degradation of this complex is induced. This new protein is termed protarg; short for proteasome-targeted protein.

The first application of the protarg system is the selective degradation of the inhibitor of apoptosis protein “survivin,” which has been characterized as a bona fide target in a wide range of solid and hematopoietic tumors. Specifically, breast cancer cells will be used to model this degradation system. A second application of the protarg system is the degradation of BCR-ABL, the protein impicated in chronic myeloid leukemia. The scope of my project is focus on the characterization of these proteasome-targeted proteins, the capability of binding endogenous protein targets, and the result (apoptosis) of cells which contain the deleterious protein.