Professor of Physiology
Dr. Munck attended the Massachusetts Institute of Technology where he was awarded a B.S. degree in 1948, and a M.S. degree in 1949, both in Chemical Engineering . After working as a chemical engineer, he returned to M.I.T. and in 1956 was awarded a Ph.D. in Biophysics. He did postdoctoral research at the Huntington Laboratory of the Massachusetts General Hospital in 1956-57 and at the Worcester Foundation for Experimental Biology from 1957 to 1959. For part of this time, he was a National Cancer Institute Fellow in Biochemistry. He joined the Department of Physiology in 1959 as an Assistant Professor and has been Professor of Physiology since 1967.
Our interest is in the molecular and physiological actions of glucocorticoids. One current project is to elucidate the relationship of phosphorylation to function of glucocorticoid receptors. We originally identified these receptors in rat thymus cells, and are now studying them in various cell lines. By phosphopeptide mapping and sequencing we have identified the phosphorylated sites. Now we are testing their function by site-directed mutagenesis. Our observations suggest that phosphorylation regulates receptor activity through the cell cycle. In S phase the receptor has low basal phosphorylation, and undergoes hormone-induced hyperphosphorylation. In G2-M phases, where proliferating cells are generally resistant to glucocorticoids, basal phosphorylation is high and there is no hormone-induced hyperphosphorylation.
Experiments with mutants indicate that the lack of hyperphosphorylation in G2-M is due to the high negative charge accompaniying high basal phosphorylation. Also of interest to us is the relation of the therapeutic actions of glucocorticoids, particularly in treatment of inflammatory diseases, to their physiological functions. Until recently it was thought that these actions, often referred to as pharmacological, are unrelated to physiology. We have proposed that they are quintessentially physiological, manifesting a major role of glucocorticoids in stress to protect the organism from its own defense mechanisms by suppressing those mechanisms, thus preventing them from overshooting and causing damage.
Hu, L.-M., Bodwell, J., Hu, J.-M., Ort’, E. and Munck, A. Glucocorticoid receptors in ATP depleted cells. Dephosphorylation, loss of hormone binding, Hsp90 dissociation, and ATP dependent cycling. J. Biol. Chem. 269:6571 (1994).
Munck, A. and Náray-Fejes-Tóth, A. Glucocorticoids and stress: permissive and suppressive actions. Ann. New York Acad. Science 746:115(1994)
Hu J-M, Bodwell JE, Munck A. Cell cycle-dependent glucocorticoid receptor phosphorylation and activity. Mol. Endocrinol 8:1709(1994)
Bodwell, JE, Hu, J-M, Hu, L-M, Munck, A 1996 Glucocorticoid receptors: ATP- and cell cycle dependence, phosphorylation, hormone resistance. Amer. J. Respir. Critical Care Med: in press.
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