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Paul W. Hruz, M.D., Ph.D.
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Assistant Professor of Pediatrics
Endocrinology and Diabetes
Developmental Biology and Genetics
Paul W. Hruz, M.D., Ph.D., works in the Division of Pediatric Endocrinology and Diabetes. Dr. Hruz, a native of Milwaukee, Wisconsin, received a bachelor's degree in chemistry from Marquette University in 1987. As a member of the Medical Scientist Training Program at the Medical College of Wisconsin, he received his Ph.D. degree in Biochemistry in 1993 and M.D. degree in 1994. Dr. Hruz then received Residency training in Pediatrics at the University of Washington in Seattle from 1994-1997. He was appointed a fellow in Pediatric Endocrinology and Diabetes at Washington University in 1997 and joined the faculty in 2000.
Dr. Hruz is board certified in Pediatrics and Pediatric Endocrinology and Metabolism. Dr. Hruz has clinical interest in a wide range of endocrine disorders, with a special interest in diabetes mellitus. He is a member of the American Academy of Pediatrics, the American Diabetes Association, the American Medical Association, the American Association for the Advancement of Science, the Endocrine Society, and the Lawson Wilkins Pediatric Endocrine Society.
Dr. Hruz's research interests include intermediary carbohydrate metabolism, glucose transporter structure and function, mechanism of insulin action, and the molecular mechanisms leading to congenital and acquired lipodystrophies. Currently, the mechanism(s) by which HIV protease inhibitors cause serious adverse metabolic effects including peripheral lipoatrophy, visceral adiposity, hypertriglyceridemia, and insulin resistance are being investigated. The laboratory has recently determined that HIV protease inhibitors selectively and reversibly inhibit the GLUT4 facilitative glucose transporter. The molecular mechanism by which this occurs in vitro is currently being studied. The tertiary structure of the facilitative glucose transporters is also being investigated by systematic cysteine-scanning mutagenesis of the 12 putative transmembrane segments within an engineered GLUT1 molecule devoid of all native cysteines. Solvent accessible residues are being determined via cysteine-directed chemical modification of each of the single cysteine mutants. In addition, the spatial proximity of each of the transmembrane segments is being investigated in double cysteine mutants by chemical cross-linking using bi-functional sulfhydryl-directed reagents.
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- B.S., Marquette University, 1987
- Ph.D., Medical College of Wisconsin, 1993
- M.D., Medical College of Wisconsin, 1994
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- Resident in Pediatrics, University of Washington, 1994-1997
- Fellow, Pediatric Endocrinology, Washington University, 1997-2000
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Hruz PW, Mueckler MM: Cysteine-Scanning Mutagenesis of Transmembrane Segment 7 of the GLUT1 Glucose Transporter. J. Biol. Chem. 1999; 274, 36176-36181.
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Murata H, Hruz PW, Mueckler MM: The Mechanism of Insulin Resistance Caused by HIV Protease Inhibitor Therapy. J. Biol. Chem. 2000; 275, 20251-20254.
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Hruz PW, Mueckler MM: Cysteine-Scanning Mutagenesis of Transmembrane Segment 11 of the GLUT1 Facilitative Glucose Transporter. Biochemistry 2000; 39, 9367-9372.
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Hruz PW, Murata H, Mueckler M: Adverse metabolic consequences of HIV protease inhibitor therapy: the search for a central mechanism. Am. J. Physiol. 2001; 280: E549-E553.
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Hruz PW, Murata H, Qiu H, Mueckler M: Indinavir induces acute and reversible peripheral insulin resistance in rats. Diabetes 2002; 51(4): 937-942.
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Koster, JC, Remidi M, Qiu H, Nichols C, Hruz PW: HIV Protease Inhibitors Acutely Impair Glucose-Stimulated Insulin Release. Diabetes 2003; 52(7): 1695-1700.
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