John Hwa

Bio Profile

John Hwa, MD, PhD

Professor of Medicine (Cardiology)

Director of Cardiovascular Pharmacogenetics

Research Interests

Anti-Inflammatory Agents, Non-Steroidal; Blood Platelets; Cardiology; Diabetes Mellitus; Pharmacogenetics; Thromboxanes

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Hwa Lab


The goals of the Hwa Laboratory are to decipher the roles played by the prostacyclin and thromboxane receptors (both G-protein coupled receptors) in the development of atherothrombosis. Both prostacyclin and thromboxane are arachidonic acid derivatives generated through the actions of cyclooxygenase (COX-1 and COX-2) enzymes.


Publications

Zou S, Teixeira AM, Kostadima M, Astle WJ, Radhakrishnan A, Simon LM, Truman L, Fang JS, Hwa J, Zhang PX, van der Harst P, Bray PF, Ouwehand WH, Frontini M, Krause DS: SNP in human ARHGEF3 promoter is associated with DNase hypersensitivity, transcript level and platelet function, and Arhgef3 KO mice have increased mean platelet volume. PLoS One. 2017; 2017 May 23. PMID: 28542600

Zou S, Teixeira AM, Yin M, Xiang Y, Xavier-Ferrucio J, Zhang PX, Hwa J, Min W, Krause DS: Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation. Thromb Haemost. 2016 Aug 30; 2016 Jun 23. PMID: 27345948

Lee SH, Du J, Stitham J, Atteya G, Lee S, Xiang Y, Wang D, Jin Y, Leslie KL, Spollett G, Srivastava A, Mannam P, Ostriker A, Martin KA, Tang WH, Hwa J: Inducing mitophagy in diabetic platelets protects against severe oxidative stress. EMBO Mol Med. 2016 Jul; 2016 Jul 1. PMID: 27221050

Xiang Y, Hwa J: Regulation of VWF expression, and secretion in health and disease. Curr Opin Hematol. 2016 May. PMID: 26771163

Seidelmann SB, Laur O, Hwa J, Depasquale E, Bellumkonda L, Sugeng L, Pomianowski P, Testani J, Chen M, McKenna W, Jacoby D: Familial dilated cardiomyopathy diagnosis is commonly overlooked at the time of transplant listing. J Heart Lung Transplant. 2016 Apr; 2015 Dec 11. PMID: 26852066

Chae WJ, Ehrlich AK, Chan PY, Teixeira AM, Henegariu O, Hao L, Shin JH, Park JH, Tang WH, Kim ST, Maher SE, Goldsmith-Pestana K, Shan P, Hwa J, Lee PJ, Krause DS, Rothlin CV, McMahon-Pratt D, Bothwell AL: The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation. Immunity. 2016 Feb 16; 2016 Feb 9. PMID: 26872695

Shao L, Zhou HJ, Zhang H, Qin L, Hwa J, Yun Z, Ji W, Min W: SENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression. Nat Commun. 2015 Nov 24; 2015 Nov 24. PMID: 26596471

Xiang Y, Cheng J, Wang D, Hu X, Xie Y, Stitham J, Atteya G, Du J, Tang WH, Lee SH, Leslie K, Spollett G, Liu Z, Herzog E, Herzog RI, Lu J, Martin KA, Hwa J: Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor. Blood. 2015 May 28; 2015 Mar 26. PMID: 25814526

Xie Y, Jin Y, Merenick BL, Ding M, Fetalvero KM, Wagner RJ, Mai A, Gleim S, Tucker DF, Birnbaum MJ, Ballif BA, Luciano AK, Sessa WC, Rzucidlo EM, Powell RJ, Hou L, Zhao H, Hwa J, Yu J, Martin KA: Phosphorylation of GATA-6 is required for vascular smooth muscle cell differentiation after mTORC1 inhibition. Sci Signal. 2015 May 12; 2015 May 12. PMID: 25969542

Obinata H, Gutkind S, Stitham J, Okuno T, Yokomizo T, Hwa J, Hla T: Individual variation of human S1P₁ coding sequence leads to heterogeneity in receptor function and drug interactions. J Lipid Res. 2014 Dec; 2014 Oct 7. PMID: 25293589

Liu R, Jin Y, Tang W, Qin L, Zhang X, Tellides G, Hwa J, Yu J, Martin KA: Response to letter regarding article, "ten-eleven translocation-2 (TET2) is a master regulator of smooth muscle cell plasticity". Circulation. 2014 Aug 19. PMID: 25135133

Keramati AR, Fathzadeh M, Go GW, Singh R, Choi M, Faramarzi S, Mane S, Kasaei M, Sarajzadeh-Fard K, Hwa J, Kidd KK, Babaee Bigi MA, Malekzadeh R, Hosseinian A, Babaei M, Lifton RP, Mani A: A form of the metabolic syndrome associated with mutations in DYRK1B. N Engl J Med. 2014 May 15. PMID: 24827035

Tang WH, Stitham J, Jin Y, Liu R, Lee SH, Du J, Atteya G, Gleim S, Spollett G, Martin K, Hwa J: Aldose reductase-mediated phosphorylation of p53 leads to mitochondrial dysfunction and damage in diabetic platelets. Circulation. 2014 Apr 15; 2014 Jan 28. PMID: 24474649

Chakraborty R, Bhullar RP, Dakshinamurti S, Hwa J, Chelikani P: Inverse agonism of SQ 29,548 and Ramatroban on Thromboxane A2 receptor. PLoS One. 2014; 2014 Jan 23. PMID: 24465800

Moore JH, Hwa J: Editorial: pharmacogenetics and molecular medicine: "so close and yet so far". Curr Mol Med. 2014. PMID: 25109800

Liu R, Jin Y, Tang WH, Qin L, Zhang X, Tellides G, Hwa J, Yu J, Martin KA: Ten-eleven translocation-2 (TET2) is a master regulator of smooth muscle cell plasticity. Circulation. 2013 Oct 29; 2013 Sep 27. PMID: 24077167

Partovian C, Li SX, Xu X, Lin H, Strait KM, Hwa J, Krumholz HM: Patterns of change in nesiritide use in patients with heart failure: how hospitals react to new information. JACC Heart Fail. 2013 Aug; 2013 Aug 5. PMID: 24621935

Gleim S, Stitham J, Tang WH, Li H, Douville K, Chelikani P, Rade JJ, Martin KA, Hwa J: Human thromboxane A2 receptor genetic variants: in silico, in vitro and "in platelet" analysis. PLoS One. 2013; 2013 Jun 28. PMID: 23840660

Kang Y, Kim J, Anderson JP, Wu J, Gleim SR, Kundu RK, McLean DL, Kim JD, Park H, Jin SW, Hwa J, Quertermous T, Chun HJ: Apelin-APJ signaling is a critical regulator of endothelial MEF2 activation in cardiovascular development. Circ Res. 2013 Jun 21; 2013 Apr 19. PMID: 23603510

Frey AJ, Ibrahim S, Gleim S, Hwa J, Smyth EM: Biased suppression of TP homodimerization and signaling through disruption of a TM GxxxGxxxL helical interaction motif. J Lipid Res. 2013 Jun; 2013 Mar 14. PMID: 23493750

Lemaire M, Frémeaux-Bacchi V, Schaefer F, Choi M, Tang WH, Le Quintrec M, Fakhouri F, Taque S, Nobili F, Martinez F, Ji W, Overton JD, Mane SM, Nürnberg G, Altmüller J, Thiele H, Morin D, Deschenes G, Baudouin V, Llanas B, Collard L, Majid MA, Simkova E, Nürnberg P, Rioux-Leclerc N, Moeckel GW, Gubler MC, Hwa J, Loirat C, Lifton RP: Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet. 2013 May; 2013 Mar 31. PMID: 23542698

Chakraborty R, Pydi SP, Gleim S, Bhullar RP, Hwa J, Dakshinamurti S, Chelikani P: New insights into structural determinants for prostanoid thromboxane A2 receptor- and prostacyclin receptor-G protein coupling. Mol Cell Biol. 2013 Jan; 2012 Oct 29. PMID: 23109431

Gleim S, Stitham J, Tang WH, Martin KA, Hwa J: An eicosanoid-centric view of atherothrombotic risk factors. Cell Mol Life Sci. 2012 Oct; 2012 Apr 11. PMID: 22491820

Tzakos AG, Kontogianni VG, Tsoumani M, Kyriakou E, Hwa J, Rodrigues FA, Tselepis AD: Exploration of the antiplatelet activity profile of betulinic acid on human platelets. J Agric Food Chem. 2012 Jul 18; 2012 Jul 3. PMID: 22720759

Tang WH, Martin KA, Hwa J: Aldose reductase, oxidative stress, and diabetic mellitus. Front Pharmacol. 2012; 2012 May 9. PMID: 22582044

Ding M, Carrão AC, Wagner RJ, Xie Y, Jin Y, Rzucidlo EM, Yu J, Li W, Tellides G, Hwa J, Aprahamian TR, Martin KA: Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype. J Mol Cell Cardiol. 2012 Feb; 2011 Sep 17. PMID: 21952104

Chakraborty R, Pydi SP, Gleim S, Dakshinamurti S, Hwa J, Chelikani P: Site-directed mutations and the polymorphic variant Ala160Thr in the human thromboxane receptor uncover a structural role for transmembrane helix 4. PLoS One. 2012; 2012 Jan 17. PMID: 22272267

Tang WH, Stitham J, Gleim S, Di Febbo C, Porreca E, Fava C, Tacconelli S, Capone M, Evangelista V, Levantesi G, Wen L, Martin K, Minuz P, Rade J, Patrignani P, Hwa J: Glucose and collagen regulate human platelet activity through aldose reductase induction of thromboxane. J Clin Invest. 2011 Nov; 2011 Oct 17. PMID: 22005299

Ding M, Xie Y, Wagner RJ, Jin Y, Carrao AC, Liu LS, Guzman AK, Powell RJ, Hwa J, Rzucidlo EM, Martin KA: Adiponectin induces vascular smooth muscle cell differentiation via repression of mammalian target of rapamycin complex 1 and FoxO4. Arterioscler Thromb Vasc Biol. 2011 Jun; 2011 Mar 31. PMID: 21454807

Stitham J, Midgett C, Martin KA, Hwa J: Prostacyclin: an inflammatory paradox. Front Pharmacol. 2011; 2011 May 13. PMID: 21687516

Stitham J, Arehart E, Elderon L, Gleim SR, Douville K, Kasza Z, Fetalvero K, MacKenzie T, Robb J, Martin KA, Hwa J: Comprehensive biochemical analysis of rare prostacyclin receptor variants: study of association of signaling with coronary artery obstruction. J Biol Chem. 2011 Mar 4; 2010 Dec 28. PMID: 21189259

García Rodríguez LA, González-Pérez A, Bueno H, Hwa J: NSAID use selectively increases the risk of non-fatal myocardial infarction: a systematic review of randomised trials and observational studies. PLoS One. 2011 Feb 8; 2011 Feb 8. PMID: 21347435

Menon I, Huber T, Sanyal S, Banerjee S, Barré P, Canis S, Warren JD, Hwa J, Sakmar TP, Menon AK: Opsin is a phospholipid flippase. Curr Biol. 2011 Jan 25; 2011 Jan 13. PMID: 21236677

Ibrahim S, Tetruashvily M, Frey AJ, Wilson SJ, Stitham J, Hwa J, Smyth EM: Dominant negative actions of human prostacyclin receptor variant through dimerization: implications for cardiovascular disease. Arterioscler Thromb Vasc Biol. 2010 Sep; 2010 Jun 3. PMID: 20522800

Gleim S, Kasza Z, Martin K, Hwa J: Prostacyclin receptor/thromboxane receptor interactions and cellular responses in human atherothrombotic disease. Curr Atheroscler Rep. 2009 May. PMID: 19361355

Kasza Z, Fetalvero KM, Ding M, Wagner RJ, Acs K, Guzman AK, Douville KL, Powell RJ, Hwa J, Martin KA: Novel signaling pathways promote a paracrine wave of prostacyclin-induced vascular smooth muscle differentiation. J Mol Cell Cardiol. 2009 May; 2009 Jan 23. PMID: 19302827

Arehart E, Gleim S, White B, Hwa J, Moore JH: Multifactor dimensionality reduction analysis identifies specific nucleotide patterns promoting genetic polymorphisms. BioData Min. 2009 Mar 30; 2009 Mar 30. PMID: 19331672

Gleim S, Stojanovic A, Arehart E, Byington D, Hwa J: Conserved rhodopsin intradiscal structural motifs mediate stabilization: effects of zinc. Biochemistry. 2009 Mar 3. PMID: 19206210

Martin KA, Gleim S, Elderon L, Fetalvero K, Hwa J: The human prostacyclin receptor from structure function to disease. Prog Mol Biol Transl Sci. 2009; 2009 Oct 7. PMID: 20374736

Ogden SK, Fei DL, Schilling NS, Ahmed YF, Hwa J, Robbins DJ: G protein Galphai functions immediately downstream of Smoothened in Hedgehog signalling. Nature. 2008 Dec 18. PMID: 18987629

Fetalvero KM, Zhang P, Shyu M, Young BT, Hwa J, Young RC, Martin KA: Prostacyclin primes pregnant human myometrium for an enhanced contractile response in parturition. J Clin Invest. 2008 Dec; 2008 Nov 20. PMID: 19033666

Martin KA, Hwa J: Shp shape: FAKs about hypertrophy. Circ Res. 2008 Oct 10. PMID: 18845815

Patrignani P, Di Febbo C, Tacconelli S, Douville K, Guglielmi MD, Horvath RJ, Ding M, Sierra K, Stitham J, Gleim S, Baccante G, Moretta V, Di Francesco L, Capone ML, Porreca E, Hwa J: Differential association between human prostacyclin receptor polymorphisms and the development of venous thrombosis and intimal hyperplasia: a clinical biomarker study. Pharmacogenet Genomics. 2008 Jul. PMID: 18551041

Liu X, Thangavel M, Sun SQ, Kaminsky J, Mahautmr P, Stitham J, Hwa J, Ostrom RS: Adenylyl cyclase type 6 overexpression selectively enhances beta-adrenergic and prostacyclin receptor-mediated inhibition of cardiac fibroblast function because of colocalization in lipid rafts. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun; 2007 Oct 13. PMID: 17934720

Arehart E, Stitham J, Asselbergs FW, Douville K, MacKenzie T, Fetalvero KM, Gleim S, Kasza Z, Rao Y, Martel L, Segel S, Robb J, Kaplan A, Simons M, Powell RJ, Moore JH, Rimm EB, Martin KA, Hwa J: Acceleration of cardiovascular disease by a dysfunctional prostacyclin receptor mutation: potential implications for cyclooxygenase-2 inhibition. Circ Res. 2008 Apr 25; 2008 Mar 6. PMID: 18323528

Stitham J, Arehart EJ, Gleim S, Douville K, MacKenzie T, Hwa J: Arginine (CGC) codon targeting in the human prostacyclin receptor gene (PTGIR) and G-protein coupled receptors (GPCR). Gene. 2007 Jul 1; 2007 Apr 1. PMID: 17481829

Fetalvero KM, Martin KA, Hwa J: Cardioprotective prostacyclin signaling in vascular smooth muscle. Prostaglandins Other Lipid Mediat. 2007 Jan; 2006 Jul 7. PMID: 17164138

Stitham J, Arehart EJ, Gleim SR, Douville KL, Hwa J: Human prostacyclin receptor structure and function from naturally-occurring and synthetic mutations. Prostaglandins Other Lipid Mediat. 2007 Jan; 2006 Jul 3. PMID: 17164137

Stitham J, Gleim SR, Douville K, Arehart E, Hwa J: Versatility and differential roles of cysteine residues in human prostacyclin receptor structure and function. J Biol Chem. 2006 Dec 1; 2006 Oct 2. PMID: 17015447

Fetalvero KM, Shyu M, Nomikos AP, Chiu YF, Wagner RJ, Powell RJ, Hwa J, Martin KA: The prostacyclin receptor induces human vascular smooth muscle cell differentiation via the protein kinase A pathway. Am J Physiol Heart Circ Physiol. 2006 Apr; 2006 Jan 6. PMID: 16399867

Kim JM, Hwa J, Garriga P, Reeves PJ, RajBhandary UL, Khorana HG: Light-driven activation of beta 2-adrenergic receptor signaling by a chimeric rhodopsin containing the beta 2-adrenergic receptor cytoplasmic loops. Biochemistry. 2005 Feb 22. PMID: 15709741

Stojanovic A, Stitham J, Hwa J: Critical role of transmembrane segment zinc binding in the structure and function of rhodopsin. J Biol Chem. 2004 Aug 20; 2004 Jun 12. PMID: 15194703

Stitham J, Stojanovic A, Ross LA, Blount AC Jr, Hwa J: Clusters of transmembrane residues are critical for human prostacyclin receptor activation. Biochemistry. 2004 Jul 20. PMID: 15248755

DiPetrillo K, Coutermarsh B, Soucy N, Hwa J, Gesek F: Tumor necrosis factor induces sodium retention in diabetic rats through sequential effects on distal tubule cells. Kidney Int. 2004 May. PMID: 15086906

Stojanovic A, Hwang I, Khorana HG, Hwa J: Retinitis pigmentosa rhodopsin mutations L125R and A164V perturb critical interhelical interactions: new insights through compensatory mutations and crystal structure analysis. J Biol Chem. 2003 Oct 3; 2003 Jul 18. PMID: 12871954

Stitham J, Stojanovic A, Merenick BL, O'Hara KA, Hwa J: The unique ligand-binding pocket for the human prostacyclin receptor. Site-directed mutagenesis and molecular modeling. J Biol Chem. 2003 Feb 7; 2002 Nov 21. PMID: 12446735

Barchowsky A, Soucy NV, O'Hara KA, Hwa J, Noreault TL, Andrew AS: A novel pathway for nickel-induced interleukin-8 expression. J Biol Chem. 2002 Jul 5; 2002 Apr 26. PMID: 11978798

Stitham J, Stojanovic A, Hwa J: Impaired receptor binding and activation associated with a human prostacyclin receptor polymorphism. J Biol Chem. 2002 May 3; 2002 Feb 19. PMID: 11854299

Stitham J, Martin KA, Hwa J: The critical role of transmembrane prolines in human prostacyclin receptor activation. Mol Pharmacol. 2002 May. PMID: 11961139

Stojanovic A, Hwa J: Rhodopsin and retinitis pigmentosa: shedding light on structure and function. Receptors Channels. 2002. PMID: 12402507

John Hwa

John Hwa, MD, PhD

Professor of Medicine (Cardiology)

Contact Info
Lab
Cardiovascular Research Center
300 George Street
New Haven, CT 06511
Academic Office
Cardiovascular Research Center
300 George Street
New Haven, CT 06511