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John Hwa, M.B.B.S., Ph.D.
Title(s):
Associate Professor of Pharmacology & Toxicology
and of Medicine (Cardiology)
Director of MPTT Graduate Program
Department(s):
Pharmacology and Toxicology
Education:
Sydney University (Australia), M.D. (M.B.B.S) 1986
Case Western Reserve University, Ph.D. 1996
Programs:
Program in Experimental and Molecular Medicine
Websites:
http://dms.dartmouth.edu/pharmtox/
http://dms.dartmouth.edu/hwa/
Contact Information:
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7650 Remsen Dept. of Pharmacology and Toxicology Dartmouth Medical School Hanover NH 03755 |
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Office: Remsen 520 Phone: 603-650-1813 Fax: 603-650-1229 Email: john.hwa@dartmouth.edu |
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Selected Publications: |
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Hwa J., Klein-Seetharaman J., Khorana H.G. Structure and function in rhodopsin: Mass spectrometric identification of the abnormal intradiscal disulfide bond in misfolded retinitis pigmentosa mutants. Proc Natl Acad Sci USA 98:4872-4876, 2001 Stitham J., Stojanovic A., Hwa J Impaired receptor binding and activation associated with a human prostacyclin receptor polymorphism. J Biol Chem 277: 15439-15444, 2002 Stitham J, Stojanovic A, Merenick BL, O'Hara K,A Hwa J. The unique ligand-binding pocket for the human prostacyclin receptor. Site-directed mutagenesis and molecular modeling. J Biol Chem. 278(6):4250-7. 2003 (view details on MedLine) Stojanovic A, Hwang I, Khorana H.G., Hwa J. Retinitis pigmentosa rhodopsin mutations Leu125Arg and Ala164Val perturb critical interhelical interactions; new insights through compensatory mutations and crystal structure analysis. J Biol Chem 3;278(40):39020-39028, 2003 Stojanovic A, Stitham J, Hwa J. Critical role of transmembrane segment zinc binding in the structure and function of rhodopsin. J Biol Chem. 20;279(34):35932-41. 2004 (Paper of the Week) (view details on MedLine) Stitham J., Gleim S.R., Douville K., Arehart E., Hwa J. Versatility and differential roles of cysteine residues in human prostacyclin receptor structure and function. J Biol Chem 281(48):37227-36 2006 (view details on MedLine) Arehart E, Gleim S, Kasza Z, Fetalvero K, Martin K.A., Hwa J. Prostacyclin atherothrombosis and cardiovascular disease. Current Medicinal Chemistry 14(20): 2161-2169 2007 (view details on MedLine) Stitham J, Arehart E.J., Gleim S.R., Li N., Douville K, Hwa J. New insights into human prostacyclin receptor function through natural and synthetic mutations of transmembrane charged residues. British Journal of Pharmacology 152(4):513-22 2007 (view details on MedLine) Arehart E, Stitham J, Asselbergs F., Douville K, MacKenzie T, Fetalvero K, Gleim S, Kasza Z, Rao Y, Martel L, Segel S, Robb J, Kaplan A, Simons M, Powell R, Moore J, Rimm E.B., Martin K, and Hwa J. Acceleration of cardiovascular disease by a dysfunctional prostacyclin receptor mutation,potential implications for COX-2 inhibition. Circ Res 102:986-993 2008 (Cover of Issue & Editors Pick) (view details on MedLine) Patrignani P, Di Febbo C, Tacconelli S, Douville K,., Guglielmi M.D., Horvath R., Ding M., Kent S., Stitham J., Gleim S., Baccante G., Moretta V., Di Francesco L., Capone M.L., Porreca E., Hwa J. Differential association between human prostacyclin receptor polymorphisms and the development of venous thrombosis and intimal hyperplasia: a clinical biomarker study. Pharmacogenetics & Genomics (in Press) 2008 |
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Professional Interests:
Pharmacogenetics of the G-protein coupled receptors; prostacyclin and thromboxane receptors and cardiovascular disease.
Dr. Hwa received his medical degree (with First Class Honors) from the University of Sydney, Sydney, Australia in 1986. He completed his Residency in Internal Medicine and Fellowship in Cardiology at the Royal Prince Alfred Hospital, Sydney, Australia, in 1992. He then pursued further studies in the Department of Molecular Cardiology at the Cleveland Clinic Foundation during which time he completed his doctoral thesis through Case Western Reserve University (1996). Dr. Hwa was then awarded a Howard Hughes Physician Postdoctoral Fellowship to continue studies at M.I.T in the laboratory of Nobel Laureate, H. Gobind Khorana. He joined the faculty of Pharmacology and Toxicology as an Assistant Professor in September, 2000.
The recent withdrawal of rofecoxib (Vioxx) due to increased cardiovascular events has highlighted the importance of the human prostacyclin and thromboxane receptors (both G-protein coupled receptors) in the development of atherothrombosis. We have thus far detected 34 genetic variants of the human prostacyclin receptor and 21 genetic variants of the thromboxane receptor in sequencing over 1,500 patient genomic samples. We aim to assess these mutations from biochemistry, to molecular pharmacology, to pathophysiology, and for clinical disease correlation. The ultimate goal will be to identify patients at increased risk for the development of cardiovascular disease, and develop prostacyclin and thromboxane based therapies.
Courses Taught:
Pharm 216 Medical and Graduate Pharmacology (Director)
Pharm 129 Molecular Pharmacology
PEMM 101/102 Core Course
Grant Information:
American Heart Association (National)
NIH-NHLBI
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