My laboratory is interested in the biology of tumor suppressor genes with particular emphasis on the von Hippel-Lindau tumor suppressor protein. This protein is a substrate receptor for the SCFVHL E3 ligase and induces tumor suppression, at least in part, by regulating the expression of hypoxia-inducible genes. A bona fide target of this complex is hypoxia-inducible factor HIF. We are currently exploring potential therapeutic implications of this known VHL-HIF interaction and, in addition, we are identifying novel substrates, which are ubiquitinated by the SCFVHL E3 ligase complex. At the clinical front we are creating a multidisciplinary VHL/Familial Renal Carcinoma clinic, staffed with professional genetic counselors and operating under the auspices of the MGH Cancer Genetics Program. We plan to co-ordinate patient care and approach the current questions regarding VHL disease monitoring, chemoprevention and timely intervention on a protocol-based manner. We also hope to enroll VHL patients in suitable treatment protocols.