Dr. Greene’s research is focused on understanding the molecular mechanisms by which SERMs (selective estrogen receptor modulators) elicit tissue-selective agonist or antagonist responses in hormone-dependent tissues and cancers via one or both estrogen receptor subtypes, ER α and ERβ. His lab is using x-ray crystallography to determine the 3-D conformations of both ERs complexed with diverse SERMs. This information is being applied to the design novel/improved SERMs that can be used to prevent or treat breast cancer and which may also have use in hormone replacement therapy for postmenopausal women. Dr. Greene has also recently initiated a complementary drug discovery program, in collaboration with Drs. DeSombre Kozmin and Mrksich, to develop novel SERMs that have improved therapeutic utility. They intend to use highly sophisticated technology to synthesize and select compounds that act differently on ER α and ERβ. Selected compounds will be subjected to a series of functional cell- and animal-based assays for their ability to inhibit mammary tumor cell growth while maintaining the known beneficial effects of estrogens in other tissues. This research has potential application to diabetes because estrogens and SERMs affect insulin-glucose homeostasis and regulate gene expression and cell function in numerous tissues that also respond to insulin or IGF-1. In addition, cross-talk between insulin-like growth factor (IGF-1R) and Er α signaling has been demonstrated in vivo. Estrogens and ER α / β are also important factors in cardiovascular disease and obesity.