Pharmacology

Jacqueline Smits

Mentor: David Wiemer, PhD

Year Entered Into Program: 2006

PhD Institution: University of Iowa, 2011

Research Description

Farnesylation of Ras proteins is a critically important step in post-translational processing which is required for the membrane association of Ras proteins. Ras proteins cycle between a GTP bound active and a GDP bound inactive state which serve as signaling molecules and regulate cell proliferation. The ability to track Ras proteins in vivo will provide information about the intracellular role of Ras and the processes that occur subsequent to the post-translational modification of these proteins. The ability to affect cell proliferation makes the Ras family proteins and the process of farnesylation interesting targets for studies aimed at the development of new anti-cancer agents.
Past research has determined bisphosphonates that incorporate isoprenoid units of farnesyl and geranyl length affect the activity of farnesyl pyrophosphate synthase and geranylgeranyl pyrophosphate synthase. My research focuses on the synthesis of bisphosphonate derivatives containing the fluorescent farnesyl substructure as well as a variety of other potentially active bisphosphonate compounds. The ability of these compounds to inhibit prenylation of proteins will be evaluated. New bisphosphonate derivatives will help develop a greater understating of the mechanism of RAS farnesylation and will lead to the design and development of novel, potential anti-cancer compounds as well as more specific agents for use in interrupting related metabolic pathways.