简介

My current NIH and NSF-funded research is on natural regulators and toxicants, and their molecular action to alter gene expression and cellular apoptosis, using an invertebrate model system to study molecular mechanisms underlying these processes. One area study funded by the National Cancer Institute is on the unusual molecular structure and action of an apoptosis inhibitor that we have newly identified from invertebrates, 'deterin,' which is a homolog of the human 'survivin' apoptosis inhibitor that is overexpressed in a wide variety of cancers. Deterin and survivn are expressed in embryonic, undifferentiated tissues, and appear to inhibit the apoptotic pathways induced by either exogenous chemical toxicants or natural endogenous regulators. A second area of hormone action is on the molecular structure and functional action of the invertebrate homolog of the retinoid X receptor, 'ultraspiracle.' Since null mutants of this receptor are lethal, our studies, including with transgenic organisms, are examining mechanistics questions on the conformation of the ligand binding pocket and the receptor's interaction with ligand and transcriptional coregulators. Development of selective agonists or antagonist compounds for this receptor to control invertebrate transmitters of disease or crop pests may provide an alternative to use of harmful pesticides in the environment that have such adverse effects on humans and other nontarget organisms (Research ca. 70% D.O.E.).