Medical Student Research Fellowship for Summer 2002

Mentor: Richard J. Auchus
Department: Internal Medicine/Endocrinology & Metabolism
Room number: Y9.308
Mail Code: 8857
Phone number: 8-6751
E-mail: richard.auchus@UTSouthwestern.edu
Project title: physiology, genetics, and biochemistry of studies of human steroid and sterol biosynthesis

Human subjects IRB approved project number (where applicable): N/A

Animal subjects IRB approved project number (where applicable): N/A

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

basic research

Brief Description of Project:

Several projects are available depending on the student's interest and background. First, our lab performs structure-function studies of human enzymes that make steroids, particularly CYP17 (17-hydroxylase/17, 20-lyase) and CYP21B (21-hydroxylase). We use a combination of computer modeling, site-directed mutagenesis, and substrate analogs to determine which residues are responsible for these enzymes' unique activities. Second, the lab studies how cytochrome b5 enhances the 17, 20-lyase activity of CYP17, which enables sex steroid production. Third, we are interested in determining the biochemical principles and structural features that govern how hydroxysteroid dehydrogenases function in living cells as primarily oxidative or reductive enzymes. Fourth, we are exploring new pathways of sex steroid formation that may explain ill-defined disorders of sexual differentiation. Fifth, we study the genetics of steroid biosynthesis, mainly patients with mutations in CYP17 causing 17-hydroxylase deficiency or isolated 17, 20-lyase deficiency. In addition, collaborative projects are available. One such project is to determine if CYP7, a bile acid biosynthetic enzyme, is a cytochrome P450 monooxygenase or actually a peroxidase, as its sequence suggests.

Previous Research Activities or Publications with Medical Students:
Tim C. Lee (now a pediatrics resident at UCLA) worked with me for a year after graduating college and during the summer after his first year in medical school (1996-1998). He and I developed our yeast system for studying enzymology of steroidogenic cytochromes P450 (Auchus et al 1998 J Biol Chem 273:3158-3165; Lee et al 1999 J Clin Endocrinol Metab 84:2104-2110). Tim received the Academic Pediatric Society/Society for Pediatric Research (APS/SPR) Student Research Award in 1999 for this work.
Kavita Vyas, a who will graduate from UT Austin in June, worked in my lab the summer of 2000, characterizing the biochemistry of novel fusion proteins to probe the mechanism of action of cytochrome b5 in the 17, 20-lyase reaction. Kavita won the award for best poster at the 39th Medical Student Research Forum, which was presented at the Endocrine Society meeting in June 2001.
Daniel Sherbet, MS1, worked in my lab last summer, characterizing a mutation in CYP17 that causes isolated 17, 20-lyase deficiency by a novel mechanism. Daniel's oral presentation at the 40th Medical Student Research Forum was selected as the best talk of the day. The work will be presented at the Endocrine Society meeting in June.
Kristen Bruce, a senior at UT Arlington, also worked in my lab last summer. She demonstrated that 17?-hydroxysteroid dehydrogenase type 1 (17?HSD1) catalyzes a reversible equilibrium reaction in living cells. She also studied (-)-progesterone (the enantiomer of progesterone) as an inhibitor of CYP17 and CYP21B. Her work on 17?HSD1 will be presented at the Endocrine Society meeting in June, and her work with (-)-progesterone is being prepared for submission to Biochemistry.

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