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The Uht laboratory analyses mechanisms by which estrogen receptors (ERs) regulate transcription in a cell specific manner. A major goal of this work is to facilitate rational drug design that would permit targeting ER-regulated malignancies without altering the function of ERs in normal tissues.
To do so, laboratory members are focusing on mechanisms by which ERs interact with cell specific chromatin microenvironments. An important group of enzymes that maintain specific environments are histone deacetylases (HDACs). These enzymes play a key role in generating chromatin environments that permit or block transcription. Of interest, a number of investigators have found that HDAC inhibitors may have therapeutic use in treatment of a variety of neoplasms. One problem with this approach, however, is that there are numerous HDACs and the inhibitors available are relatively non-specific. One way to achieve specificity would be to target individual ER/HDAC interactions. Work in the lab indicates that indeed ER-alpha interacts differently with two different HDACs of the same class. Thus, ER ligands and HDAC inhibitors could be used in combined therapies and/or, a specific ER/HDAC interface could be targeted.
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