The focus of my research group is the understanding of the tumorigenesis of renal cell carcinoma.  Our approach utilizes genetically engineered murine embryonic stem (ES) cells genetically engineered to express clinically important point mutations in the von Hippel-Lindau (VHL) tumor suppressor gene, which is mutated in over 70% of renal cancers.  These cell lines provide a tool for the in vitro study of cellular VHL activity in the absence of competing mutations as well as the ability to create a number of animal model systems for tumor growth and development.  Using this panel of ES cells we are able to investigate the effects of VHL on processes integral to tumorigenesis including angiogenesis, vasculogenesis, hypoxic response signaling, extracellular matrix remodeling, and cell cycle signaling.  These genetically targeted cells additionally provide the platform for the generation of a series of VHL mutant mice as an in vivo model of the human disease.  Our cell culture and mouse models provide excellent models for exploring the pathogenesis of renal cancer as well as serving as tools for drug development. 

Clinically, my focus is the treatment of renal cell carcinoma.  Very few agents have shown efficacy for patients with advanced stage disease.  Using the information we are able to glean from the experimental models in the laboratory our goal is to provide superior care to patients with renal cell carcinoma, and to use those models to support a program of drug discovery targeting this particular cancer.  To that end, I oversee a clinical research program within the multidisciplinary genitourinary oncology group that offers biologically active treatment protocols to patients with renal cell carcinoma at all stages of disease.