Jan-Ake Gustafsson

University of Houston


Election Year: 2002
Primary Section: 42, Medical Physiology and Metabolism
Membership Type: Foreign Associate

Research Interests

As a molecular endocrinologist I have studied mechanisms of steroid hormone action. My laboratory purified the first nuclear receptor (the glucocorticoid receptor GR) to homogeneity. We defined the three-domain structure of GR, laying the basis for much of our current understanding of nuclear receptor structure. In collaboration with Keith Yamamoto my laboratory found specific binding of GR to the glucocorticoid responsive MMTV genome. The specific DNA binding sites for GR turned out to functionally represent glucocorticoid response elements, a novel concept at the time. Continued collaboration with Yamamoto led to the first (partial) cloning of a nuclear receptor (GR), based on antibodies developed in my laboratory. In collaboration with structural biochemists I solved the 3-D structure of the GR DNA-binding domain (DBD), which turned out to be representative of all other nuclear receptor DBDs. Structural work on the ligand-binding domain of estrogen receptor ER alpha revealed the molecular mechanism of estrogen antagonism. More recently my interest in estrogen signaling has deepened, following the discovery in my laboratory of ER beta. This receptor has important functions in reproduction, the central nervous system, the cardiovascular system, and hematopoiesis.

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