John Hwa MD, PhD
Associate Professor of Medicine (Cardiology); Director of Cardiovascular Pharmacogenetics
Platelets; Diabetes Mellitus; Atherothrombosis; Prostacyclin; Thromboxane; NSAIDs
We wish to determine why patients with diabetes mellitus have increased vascular thrombosis. We use a combination of approaches including molecular signaling, biochemistry, genomics and proteomics on both human subjects and animal models. The ultimate goal is to develop novel mechanistic based therapies.
Extensive Research Description
The Hwa Laboratory research interests are on eicosanoids and diabetes mellitus, and include a number of large collaborative efforts within Yale and externally. All are focused in the broad areas of eicosanoids, NSAIDs and the development of thrombus on a background of atherosclerosis (atherothrombosis). Our studies extend from fundamental structure function of GPCRs, to pharmacogenetics, molecular signaling, pathophysiology, and clinical outcomes. For our studies we use a number of models including tissue culture cells, platelets, vascular smooth muscle cells, mouse knockout and transgenics, and recruited human patients. Our current studies can be broadly divided into the following major areas.
1) Pharmacogenetics of the prostanoid receptors
2) Platelet dysfunction in diabetes mellitus
3) miRNA regulation of thrombosis
4) The Yale cardiovascular tissue repository collaborative effort
- Tang W.H., Stitham J., Liu R., Gleim S., Spollett G., Martin K., Hwa J. Hyperglycemia promotes platelet apoptosis through a unique pathway involving aldose reductase, ROS, p53 and Bcl-xl. Circulation 2014 129(15):1598-609
- Keramati A.R., Fathzadeh M., Singh R., Choi M., Faramarzi S., Mane S., Kasaei M., Sarajzadeh-Fard K., Hwa J., Kidd K.K., Babaee Bigi M.A., Malekzadeh R., Hosseinian A., Babaie M, Lifton R.P., Mani A.. Altered function of Dyrk1B is Associated with a Highly Penetrant Form of Obesity, Atherosclerosis and their Metabolic Risk Factors. N Engl J Med 2014 370(20):1909-19
- Liu R, Yu J, Jin Y, Tang W, Qin L, Zhang X, Tellides G, Hwa J, Martin KA. TET2 is an mTORC1-dependent master regulator of vascular smooth muscle plasticity. Circulation 2013, 128(18):2047-57
- Lemaire M., Fremeaux-Bacchi V., Schaeffer F., Choi M., Tang W.H., Taque S., Nobili F., Martinez F., Ji W., Overton J.D., Mane S.M., Fakhouri F., Adra A.L., Deschenes G., Baudoin V., Llanas B., Collard L., Majid M.A., Simkova E., Nuernberg P., Rioux-Leclerc N., Moeckel G.W., Gubler M.C., Hwa J., Loirat C., & Lifton R.P. Recessive mutations in diacylglycerol kinase epsilon cause atypical hemolytic-uremic syndrome. Nature Genetics 2013 45(5):531-6
- Tang WH, Stitham J, Gleim S, Febbo C.D., Porreca E., Fava C, Tacconelli S, Capone M, Evangelista V, Levantesi G, Wen L., Martin K.A., Minuz P, Rade J, Patrignani P, Hwa J. Glucose and collagen regulate platelet activity through aldose reductase induction of thromboxane; implications for diabetes mellitus. J Clin Inves 2011 121(11):4462-76