Dr. Dawn E. Quelle, an Associate Professor of Pharmacology and Pathology, has received an OVPR award entitled "Drug Resistance in Pancreatic Cancer." Dr. James Mezhir, an Assistant Professor of Surgery, is a Co-Investigator on this grant. Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest human cancers, is characterized by ineffectual treatments and an absence of biomarkers to predict patient responsiveness to promising therapeutics. This cross-disciplinary study seeks to define the mechanisms and biological significance of RABL6A-mediated resistance to oxaliplatin in PDAC. Through molecular studies in PDAC cells, pre-clinical studies in mice and analyses of patient tumors, this work will establish if RABL6A is a clinically meaningful PDAC biomarker of oxaliplatin sensitivity. Positive results may alter the medical management of PDAC patients to include analyses of RABL6A status in patient biopsies, which could dictate the choice of the chemotherapeutic regimen.

Dr. Rory Fisher, Professor of Pharmacology and Internal Medicine has received an OVPR grant entitled "Biological and Chemical Approaches to Validating and Targeting RGS6 as a Novel Alcohol Abuse Treatment."  This project is based upon his laboratory's discovery of a new gene, RGS6, which is critically involved in alcohol dependence in mice.  Given that RGS6 is capable of regulating multiple Gai/o-coupled receptors implicated in alcohol seeking behavior and dependence, understanding the mechanism(s) underlying the reduction in alcohol consumption in mice lacking RGS6 is imperative.  No effective drugs are available to treat alcoholism.   Thus the goals of this work are multifaceted. Dr. Fisher's lab staff seek to provide novel mechanistic insight into the pathogenesis of alcoholism by elucidating the role of RGS6 in this process.  In addition, in collaboration with Dr. Roman’s group, novel small molecule inhibitors of RGS6 will be identified that will be tested for their ability to attenuate RGS6-dependent alcohol seeking behavior and dependence in mice.  If successful this project would yield new biological insights into alcohol dependence and provide novel pre-therapeutic lead molecules for future drug development for alcoholism.