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Richard A. Gibbs

Professor Richard A. Gibbs graduated from Johns Hopkins University in 1983 with a BS in Natural Sciences.  Rich obtained his Ph. D. in 1988 from University of California - Riverside for work on Vitamin D analogs and the development of new synthetic methods with Professor Bill Okamura. He was an NSF postdoctoral fellow at Penn State University from 1988-1991, where he performed catalytic antibody research with Professor Steve Benkovic. Rich began his academic career in 1992 in the Department of Pharmaceutical Sciences at Wayne State University.  As an Assistant and Associate Professor Rich made seminal contributions to the areas of medicinal and bioorganic chemistry, and the synthesis and mechanistic evaluation of anticancer drugs. Rich continued this research throughout his tenure at Wayne State and at Purdue University, where he moved to in 2001 as a Professor of Medicinal Chemistry and Molecular Pharmacology. He also served as the Associate Dean for Graduate Programs in the College of Pharmacy at Purdue.  

Rich’s research was focused on mechanistic and inhibitory studies of protein prenyltransferases and related enzyme targets, and the design and synthesis of chemical probes of protein prenylation.  Many key signal transduction proteins are modified by prenylation of a cysteine residue, followed by a specific proteolytic cleavage step and finally methylation. This has led to intense interest in protein-farnesyl transferase (FTase) inhibitors as potential cancer chemotherapeutic agents, and such compounds are currently in human clinical trials. Rich’s laboratory employed chemical biology approaches to address two key questions in the field of protein prenylation. They explored the substrate specificity of FTase, with the goal of developing potential isoprenoid-based inhibitors or modulators of protein prenylation. Secondly, they used synthetic isoprenoid analogues and labeled derivatives as probes of the biological function of protein prenylation. Rich also developed a new stereospecific route to isoprenoids to synthesize novel, specifically substituted analogues of FPP, the isoprenoid substrate of FTase. This program led to the development of a series of potent inhibitors of FTase and farnesol analogues that are potent inhibitors of the growth of certain human tumor cells in vitro.

In one example of this research program, Rich explored the posttranslational modifications of the signaling protein K-Ras, a protein that is modified post-translationally via sequential prenylation, proteolysis, and α-carboxyl methylation reactions. Both prenylation, which is catalyzed by a soluble prenyltransferase, and methylation, which is catalyzed by a membrane-associated isoprenylcysteine carboxyl methyltransferase (Icmt), are key modifications for the proper localization and biological function of K-Ras.  Since mutant K-Ras proteins are key drivers in several human cancers, including ~90% of human pancreatic carcinomas, Rich was very interested in developing inhibitors of the human Icmt-dependent methylation of K-Ras as a way to block its activity in tumor cells. In collaboration with Professor Christine Hrycyna, Rich developed a readily-synthesized class of nanomolar human Icmt (hIcmt) inhibitors based on the substrate N-acetyl-farnesyl cysteine. Structure activity relationship studies led to led to a lead compound, sTAB-F3-Diol, which has a Ki of approximately 50 nM against hIcmt.  sTAB-F3-Diol also blocked cellular Ras activation, interfered with Ras signaling through Erk, and exhibited nanomolar to low micromolar IC50 values versus pancreatic tumor cells in both 2D and 3D cell culture systems.  Further optimization of the biochemical activity and drug-like characteristics of this promising agent resulted in a new molecule with a Ki value of ~25 nM against human Icmt in in vitro enzymatic assays.  

Rich’s awards for research include an American Cancer Society Junior Faculty Research Award, the PhRMA Foundation Research Award, the Lions Club Purdue Cancer Center Research Award and the University Faculty Scholar Award from Purdue University, and for his excellence in teaching he was awarded the Instructor of the Year in the College of Pharmacy, and the College of Pharmacy and Allied Health Professions Excellence in Teaching Award at Wayne State. Rich was always very interested in the application of his work to cancer treatment and was awarded a number of patents focused on his designed inhibitors.  

Rich’s service to the medicinal chemistry community was truly exemplary.  Highlights of this dedicated service include:  Chair, Division of Medicinal Chemistry, American Chemical Society (2006); Vice Chair, Division of Medicinal Chemistry, American Chemical Society (2005); Academic Councilor, Division of Medicinal Chemistry, American Chemical Society (2008-2013); Member, Long Range Planning Committee, Division of Medicinal Chemistry, American Chemical Society (2003-2005); Chair, Awards Symposium, 231st National Meeting of American Chemical Society (2006); Chair, Medicinal Chemistry Award Symposium, National Medicinal Chemistry Symposium (2006); Chair and Organizer, Robertson and MEDI Fellowship Awards Symposium (2006); Member, Organizing Committee – First Annual Indiana Medicinal Chemistry Symposium (2010); Member, Organizing Committee – 3rd Frontiers in Medicinal Chemistry Meeting (2013); Editorial Advisory Board Member, Seventh Edition of Burger’s Medicinal Chemistry and Drug Discovery (2007); Program Leader, Medicinal Chemistry Program, Purdue Cancer Center (2006-2013); Chair, PULSe Executive Committee, Purdue University (2010-2012); Co-chair, National ACS meeting in Anaheim "SERMS" Symposium (2004); Co-chair, National ACS meeting in Philadelphia "Pharmacoproteomics" Symposium (2004); Co-chair, National ACS meeting "Druggable Targets in Functional Lipidomics" symposium (2005); and Program Chair of the 2004 Midwest Enzyme Chemistry Conference.

The field of medicinal chemistry lost one of its cherished colleagues when Rich passed away in February of 2014 after a battle with pancreatic cancer.  He is survived by his wife Barbara (Schuster) Gibbs.

ACS Division of Medicinal Chemistry

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