 James L. Thomas, Ph.D., Associate Professor, Division of Basic Medical Sciences and Department of Obstetrics & Gynecology, Mercer University School of Medicine, was recently awarded a competitive continuation of his NIH R01 grant, Placental 3β-Hydroxysteroid Dehydrogenase Isomerase, from 2/1/2005-1/31/2009 in the amount of $928,000. Dr. Thomas has been funded by this NIH grant to study this steroid-metabolizing enzyme since 1985.
Dr. Thomas developed a strong interest in biomedical research during the summers of his high school and college years. After completing a Chemistry major at Emory University, he attended the University of Alabama at Birmingham to obtain a Ph.D. in Pharmacology with a minor in Biochemistry. His postdoctoral work at Washington University School of Medicine focused on the study of steroid-metabolizing enzymes, where he specialized in the design and characterization of enzyme inhibitors. He developed the original purification of 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD) from human placenta and has used affinity labeling substrate and cofactor analogs as well as site-directed mutagenesis to study the bifunctional enzyme protein. Dr. Thomas left Washington University in St. Louis in 2000 to join the faculty at Mercer University School of Medicine.
 The objective of his research is to define the reaction mechanisms of human 3β-HSD by relating structure to function. 3β-HSD is the "gateway" enzyme in all steroidogenic tissues. Precursor steroids (pregnenolone, dehydroepiandrosterone, 17α-hydroxypregnenolone) must be converted by this enzyme to ultimately become the active steroid hormones: progesterone, estradiol, testosterone, cortisol and aldosterone. Two genes express the enzyme in a tissue-specific manner in humans. One gene expresses the type 1 3β-HSD in placenta, mammary gland, prostate, and in breast and prostate tumors. The other gene expresses the type 2 3β-HSD in the adrenals, testes and ovaries. He determined that there are profound differences in the utilization of substrates and inhibitors by the two isoenzymes. Mutagenesis of targeted amino acids in the type 1 and 2 enzymes have identified key structure/function relationships and evaluate why the two isoenzymes exhibit kinetic differences. He also has used mutagenesis to convert the enzyme from a membrane-bound form to a soluble protein that crystallizes for structural analysis. After the structural basis for the kinetic differences are determined, drugs can be developed to selectively inhibit the type 1 enzyme that is expressed in placenta to control the timing of labor as well as in breast and prostate tumors to slow their growth.
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