News and Events BMDCR
Geoffrey Greene, Ph.D. publishes results on THC antagonism of the estrogen receptor in Nature Structural Biology
Geoffrey Greene, Ph.D., Professor in and Associate Director of the Ben May Department for Cancer Research, has published exciting results in the April on-line issue (and May print edition) of Nature Structural Biology on the role a small molecule in estrogen receptor antagonism. The small molecule, THC, antagonizes ER subtype beta via a novel mechanism, blocking the receptor's ability to stimulate transcription without physically obstructing conformational changes required by this receptor for activity. This insight into such non-classical antagonism of nuclear receptors suggests a new approach to designing unique subtype-selective modulators by tailoring compounds to selectively stabilize inactive conformations of certain nuclear receptor subtypes and the active conformations of others. The paper can be accessed on-line at:
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nsb/journal/v9/n5/abs/nsb787.html.
A highlight article describing the paper can be found in Nature Reviews Drug Discovery at:
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrd/journal/v1/n5/full/nrd808_fs.html.
Dr. Greene is internationally recognized for his many contributions to the field of steroid hormone action and breast cancer. In particular, he is known for the development of antibodies to the human estrogen (ER-alpha) and progesterone (PR) receptors and their extensive use in the dissection of receptor structure and function, as well as for the measurement and analysis of both receptors in hormone dependent tissues and cancers. The resulting commercially available immunocytochemical assays for ER-alpha and PR have had widespread diagnostic application in breast cancer throughout the world. Dr. Greene is also jointly responsible for the cloning and characterization of the ER-alpha and PR genes. His most recent contribution to breast cancer molecular biology was the determination of the crystallographic structures of the human ER-alpha hormone-binding domain bound to diethylstilbestrol and to 4-hydroxytamoxifen, which has provided a molecular explanation for how certain estrogen agonists and antagonists elicit their diverse actions via the estrogen receptor. During the past 27 years, he has published more than 155 papers and has received numerous awards, including the Ernst Oppenheimer award from the Endocrine Society, the first Tartikoff-Semel award for his pioneering work and many contributions to the field of human breast cancer, and the John Brewer Distinguished Alumni Lectureship award at Northwestern University.