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Faculty Profile Last Modified Time: 09:18:18 AM Tue, 7 Apr 2020   Contact Information Jan-Ake Gustafsson Associated Profiles  Robert A. Welch Professor, Biology and Biochemistry, University of Houston   Science & Engineering Research Center, Room No.: 3027    jgustafsson@uh.edu     (832) 842-8803    Web Link    Lab Webpage    Breast Cancer, Nuclear Receptors, Estrogen Receptors, Steroid Hormone Receptors, Nuclear Receptors    Associated Profiles Research and Expertise Affiliations Appointments  Research and Expertise Research Interests   Jan-Åke Gustafsson is a leading scientist within the field of steroid hormone receptors/nuclear receptors. Several of his achievements have lead to true paradigm shifts in the field and represent breakthrough discoveries. He was first to show that a nuclear receptor, the glucocorticoid receptor, is composed of three separate structural and functional domains, a ligand binding domain, a DNA binding domain and a third domain identified by Gustafsson and coworkers by its immunogenic properties. Furthermore, the Gustafsson lab was first to purify a nuclear receptor, the glucocorticoid receptor, to homogeneity and thereby to show that it represents a single molecular species rather than a complex of multiple smaller subunits. At the time, this was an especially important finding since the literature was muddled with misconcepts based on impure and/or partially proteolyzed receptor preparations. Also, access to homogeneous nuclear receptor made it possible for Gustafsson to demonstrate specific DNA binding of glucocorticoid receptor to a glucocorticoid sensitive gene, the murine mammary tumour virus. This theretofore impossible achievement spurred a new, mechanistic era in nuclear receptor research, since in follow-up studies, Gustafsson et al could show that the specific glucocorticoid binding sites also represent glucocorticoid response elements, able to confer hormone responsiveness onto nearby genes. It is essential to point out that all of the above, absolutely central discoveries were made prior to cloning of nuclear receptors. Furthermore, Gustafsson et al cloned the first (partial) cDNA of a nuclear receptor, the glucocorticoid receptor; the unique probes making this possible were the poly- and monoclonal antibodies against the glucocorticoid receptor developed by the Gustafsson lab. Another important milestone was the structure determination of the DNA-binding domain of the glucocorticoid receptor, the first ever nuclear receptor structure to be solved. During the recent fifteen years, Gustafsson has continued to be responsible for paradigm shifts in the field of nuclear receptor research. It was Gustafsson who first identified physiological ligands for a so called "orphan receptor", namely fatty acids for the peroxisome proliferator activated receptor (PPAR), thereby integrating fatty acids into molecular endocrinology. Furthermore, Gustafsson discovered OR-1, later renamed LXR², an oxysterol activated nuclear receptor of paramount significance in e g regulation of cholesterol homeostasis and brain development. Finally, and most importantly, Gustafsson and colleagues made the completely unexpected discovery of estrogen receptor ², a second estrogen receptor which has turned out to have functions far outside reproductive physiology and to be a very promising target in pharmaceutical development of novel drugs.  Publications/Creative Works Click here to search for this faculty member's publications on PubMed.  Affiliations  Training Grants Computational Cancer Biology Training Program  Appointments Title Department / School Institution Robert A. Welch Professor Biology and Biochemistry University of Houston

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