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Walter J. Koch, PhD

Walter J. Koch, PhD

 

William Wikoff Smith Endowed Chair in Cardiovascular Medicine

Chairperson, Pharmacology

Professor, Pharmacology

Professor, Center for Translational Medicine

Director, Center for Translational Medicine

Telephone:  215-707-9820

Fax:  215-707-9890

Email: walter.koch@temple.edu

 

Department of Pharmacology

Center for Translational Medicine

 

Educational Background:

 

 

BS, Pharmacy (Cum Laude), University of Toledo College of Pharmacy, Toledo, OH, 1984

 

PhD, Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH, 1990

 

Howard Hughes Medical Institute Postdoctoral Fellowship, Duke University Medical Center (laboratory of Dr. Robert J. Lefkowitz), 1991-1995

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professional affiliations:

 

  • Member, Heart Failure Society of America, 2000-present
  • Member, American Society of Gene and Cell Therapy, 2000-present
  • Member, American Society for Pharmacology and Experimental Therapeutics, 1998-present
  • Member, International Society for Heart Research, 1997-present
  • Member, American Society for Biochemistry and Molecular Biology, 1994-present
  • Member, Basic Science Council, American Heart Association, 1994-present
  • Professional Member, American Heart Association, 1994-present

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Research Interests:

 

The Koch laboratory currently is investigating molecular mechanisms involved in the regulation of signaling through cardiovascular adrenergic receptors (ARs) and the role this plays in heart disease, primarily heart failure (HF). The lab s research primarily targets a family of kinases known to regulate ARs and other G protein-coupled receptors (GPCRs) known as the GPCR kinases (GRKs). These GRKs appear to be critically involved in normal and failing heart function and we are manipulating the expression and activity of GRKs in the cardiovascular system. To do this, we utilize novel genetically engineered mouse models and also adenoviral-mediated myocardial gene delivery. Signaling information delineated to be involved in the pathogenesis of heart disease is utilized to design potential novel molecular therapeutic strategies for heart disease. This includes an ultimate goal of the laboratory to develop gene therapy protocols for HF utilizing novel intracoronary delivery techniques. These delivery techniques as well as "proof of concept" testing of molecular targets in the heart are currently being carried out in vivo in models of HF. In addition to HF, programs are ongoing in the laboratory to investigate novel ways to protect the heart against ischemia-induced myocyte apoptosis and also molecular ways to improve the function of the transplanted human heart. Another program in the lab is the investigation of the role of GPCR signaling in pathological vascular smooth muscle proliferation such as what occurs during arterial restenosis following angioplasty. New directions in the lab have us interested in novel non-GPCR binding partners for GRKs and are using a variety of in vitro techniques to discover and investigate these with a future plan to determine any cardiovascular physiological relevance of these GRK targets.

    

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

25340299. Homan KT, Wu E, Cannavo A, Koch WJ, Tesmer JJ, Identification and Characterization of Amlexanox as a G Protein-Coupled Receptor Kinase 5 Inhibitor. Molecules 19:10(16937-16949)2014 Oct 22

25340284. Scimia MC, Sydnes KE, Zuppo DA, Koch WJ, Methods to improve cardiac gene therapy expression. Expert Rev Cardiovasc Ther 12:11(1317-1326)2014 Nov

25332207. Hullmann JE, Grisanti LA, Makarewich CA, Gao E, Gold JI, Chuprun JK, Tilley DG, Houser SR, Koch WJ, GRK5-Mediated Exacerbation of Pathological Cardiac Hypertrophy Involves Facilitation of Nuclear NFAT Activity. Circ Res :()2014 Oct 20

25277999. He Q, Pu J, Yuan A, Lau WB, Gao E, Koch WJ, Ma XL, He B, Activation of LXRa but not LXR Protects Against Myocardial Ischemia/Reperfusion Injury. Circ Heart Fail :()2014 Oct 2

25239306. Lucas E, Jurado-Pueyo M, Fortuo MA, Fernndez-Veledo S, Vila-Bedmar R, Jimnez-Borreguero LJ, Lazcano JJ, Gao E, Gmez-Ambrosi J, Frhbeck G, Koch WJ, Dez J, Mayor F Jr, Murga C, Downregulation of G protein-coupled receptor kinase 2 levels enhances cardiac insulin sensitivity and switches on cardioprotective gene expression patterns. Biochim Biophys Acta :()2014 Sep 18

25205804. Tilley DG, Zhu W, Myers VD, Barr LA, Gao E, Li X, Song J, Carter RL, Makarewich CA, Yu D, Troupes CD, Grisanti LA, Coleman RC, Koch WJ, Houser SR, Cheung JY, Feldman AM, -Adrenergic Receptor-Mediated Cardiac Contractility is Inhibited via Vasopressin Type 1A-Receptor-Dependent Signaling. Circulation :()2014 Sep 9

24852843. Yan W, Zhang F, Zhang R, Zhang X, Wang Y, Zhou F, Xia Y, Liu P, Gao C, Wang H, Zhang L, Zhou J, Gao F, Gao E, Koch WJ, Wang H, Cheng H, Qu Y, Tao L, Adiponectin regulates SR Ca(2+) cycling following ischemia/reperfusion via sphingosine 1-phosphate-CaMKII signaling in mice. J Mol Cell Cardiol 74:(183-92)2014 Sep

24816261. Carbe CJ, Cheng L, Addya S, Gold JI, Gao E, Koch WJ, Riobo NA, Gi proteins mediate activation of the canonical hedgehog pathway in the myocardium. Am J Physiol Heart Circ Physiol 307:1(H66-72)2014 Jul 1

24812353. Woodall MC, Ciccarelli M, Woodall BP, Koch WJ, G protein-coupled receptor kinase 2: a link between myocardial contractile function and cardiac metabolism. Circ Res 114:10(1661-70)2014 May 9

24794045. Scimia MC, Blass BE, Koch WJ, Apelin receptor: its responsiveness to stretch mechanisms and its potential for cardiovascular therapy. Expert Rev Cardiovasc Ther 12:6(733-41)2014 Jun

24702056. Huang ZM, Gao E, Chuprun JK, Koch WJ, GRK2 in the Heart: A GPCR Kinase and Beyond. Antioxid Redox Signal :()2014 May 13

24683488. Carter RL, Grisanti LA, Yu JE, Repas AA, Woodall M, Ibetti J, Koch WJ, Jacobson MA, Tilley DG, Dynamic mass redistribution analysis of endogenous -adrenergic receptor signaling in neonatal rat cardiac fibroblasts. Pharmacol Res Perspect 2:1()2014 Feb

24521102. Brailoiu GC, Deliu E, Rabinowitz JE, Tilley DG, Koch WJ, Brailoiu E, Urotensin II promotes vagal-mediated bradycardia by activating cardiac-projecting parasympathetic neurons of nucleus ambiguus. J Neurochem 129:4(628-36)2014 May

24486513. Wang J, Song J, Gao E, Zhang XQ, Gu T, Yu D, Koch WJ, Feldman AM, Cheung JY, Induced overexpression of phospholemman S68E mutant improves cardiac contractility and mortality after ischemia-reperfusion. Am J Physiol Heart Circ Physiol 306:7(H1066-77)2014 Apr 1

24430870. Hoffman NE, Chandramoorthy HC, Shanmughapriya S, Zhang XQ, Vallem S, Doonan PJ, Malliankaraman K, Guo S, Rajan S, Elrod JW, Koch WJ, Cheung JY, Madesh M, SLC25A23 augments mitochondrial Ca? uptake, interacts with MCU, and induces oxidative stress-mediated cell death. Mol Biol Cell 25:6(936-47)2014 Mar

24401846. Deliu E, Brailoiu GC, Eguchi S, Hoffman NE, Rabinowitz JE, Tilley DG, Madesh M, Koch WJ, Brailoiu E, Direct evidence of intracrine angiotensin II signaling in neurons. Am J Physiol Cell Physiol 306:8(C736-44)2014 Apr 15

24397980. Wang Y, Wang X, Lau WB, Yuan Y, Booth D, Li JJ, Scalia R, Preston K, Gao E, Koch W, Ma XL, Adiponectin inhibits tumor necrosis factor-a-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation. Circ Res 114:5(792-805)2014 Feb 28

24388546. Rengo G, Pagano G, Parisi V, Femminella GD, de Lucia C, Liccardo D, Cannavo A, Zincarelli C, Komici K, Paolillo S, Fusco F, Koch WJ, Perrone Filardi P, Ferrara N, Leosco D, Changes of plasma norepinephrine and serum N-terminal pro-brain natriuretic peptide after exercise training predict survival in patients with heart failure. Int J Cardiol 171:3(384-9)2014 Feb 15

24361238. Kaikkonen L, Magga J, Ronkainen VP, Koivisto E, Perjes , Chuprun JK, Vinge LE, Kilpi T, Aro J, Ulvila J, Alakoski T, Bibb JA, Szokodi I, Koch WJ, Ruskoaho H, Kerkel R, p38a regulates SERCA2a function. J Mol Cell Cardiol 67:(86-93)2014 Feb

24334028. Kim IM, Wang Y, Park KM, Tang Y, Teoh JP, Vinson J, Traynham CJ, Pironti G, Mao L, Su H, Johnson JA, Koch WJ, Rockman HA, -arrestin1-biased 1-adrenergic receptor signaling regulates microRNA processing. Circ Res 114:5(833-44)2014 Feb 28

24328708. Scimia MC, Gumpert AM, Koch WJ, Cardiovascular gene therapy for myocardial infarction. Expert Opin Biol Ther 14:2(183-95)2014 Feb

24315785. Brinks H, Giraud MN, Segiser A, Ferri C, Longnus S, Ullrich ND, Koch WJ, Most P, Carrel TP, Tevaearai HT, Dynamic patterns of ventricular remodeling and apoptosis in hearts unloaded by heterotopic transplantation. J Heart Lung Transplant 33:2(203-10)2014 Feb

24305416. Weber C, Neacsu I, Krautz B, Schlegel P, Sauer S, Raake P, Ritterhoff J, Jungmann A, Remppis AB, Stangassinger M, Koch WJ, Katus HA, Mller OJ, Most P, Pleger ST, Therapeutic safety of high myocardial expression levels of the molecular inotrope S100A1 in a preclinical heart failure model. Gene Ther 21:2(131-8)2014 Feb

24174526. Islam KN, Bae JW, Gao E, Koch WJ, Regulation of nuclear factor ?B (NF-?B) in the nucleus of cardiomyocytes by G protein-coupled receptor kinase 5 (GRK5). J Biol Chem 288:50(35683-9)2013 Dec 13

24170934. Huang ZM, Gao E, Fonseca FV, Hayashi H, Shang X, Hoffman NE, Chuprun JK, Tian X, Tilley DG, Madesh M, Lefer DJ, Stamler JS, Koch WJ, Convergence of G protein-coupled receptor and S-nitrosylation signaling determines the outcome to cardiac ischemic injury. Sci Signal 6:299(ra95)2013 Oct 29

24133451. Cannavo A, Liccardo D, Koch WJ, Targeting cardiac -adrenergic signaling via GRK2 inhibition for heart failure therapy. Front Physiol 4:(264)2013 Sep 26

24030395. Zhao J, Wang F, Zhang Y, Jiao L, Lau WB, Wang L, Liu B, Gao E, Koch WJ, Ma XL, Wang Y, Sevoflurane preconditioning attenuates myocardial ischemia/reperfusion injury via caveolin-3-dependent cyclooxygenase-2 inhibition. Circulation 128:11 Suppl 1(S121-9)2013 Sep 10

24030394. Sun Y, Yi W, Yuan Y, Lau WB, Yi D, Wang X, Wang Y, Su H, Wang X, Gao E, Koch WJ, Ma XL, C1q/tumor necrosis factor-related protein-9, a novel adipocyte-derived cytokine, attenuates adverse remodeling in the ischemic mouse heart via protein kinase A activation. Circulation 128:11 Suppl 1(S113-20)2013 Sep 10

24029943. Gao E, Koch WJ, A novel and efficient model of coronary artery ligation in the mouse. Methods Mol Biol 1037:(299-311)2013

24002692. Khan M, Mohsin S, Toko H, Alkatib M, Nguyen J, Truffa S, Gude N, Chuprun K, Tilley DG, Koch WJ, Sussman MA, Cardiac progenitor cells engineered with ARKct have enhanced -adrenergic tolerance. Mol Ther 22:1(178-85)2014 Jan

23984926. Scimia MC, Cannavo A, Koch WJ, Gene therapy for heart disease: molecular targets, vectors and modes of delivery to myocardium. Expert Rev Cardiovasc Ther 11:8(999-1013)2013 Aug

23969695. Cannavo A, Rengo G, Liccardo D, Pagano G, Zincarelli C, De Angelis MC, Puglia R, Di Pietro E, Rabinowitz JE, Barone MV, Cirillo P, Trimarco B, Palmer TM, Ferrara N, Koch WJ, Leosco D, Rapacciuolo A, 1-adrenergic receptor and sphingosine-1-phosphate receptor 1 (S1PR1) reciprocal downregulation influences cardiac hypertrophic response and progression to heart failure: protective role of S1PR1 cardiac gene therapy. Circulation 128:15(1612-22)2013 Oct 8

23878371. Brailoiu GC, Benamar K, Arterburn JB, Gao E, Rabinowitz JE, Koch WJ, Brailoiu E, Aldosterone increases cardiac vagal tone via G protein-coupled oestrogen receptor activation. J Physiol 591:Pt 17(4223-35)2013 Sep 1

23860374. Ali MS, Starke RM, Jabbour PM, Tjoumakaris SI, Gonzalez LF, Rosenwasser RH, Owens GK, Koch WJ, Greig NH, Dumont AS, TNF-a induces phenotypic modulation in cerebral vascular smooth muscle cells: implications for cerebral aneurysm pathology. J Cereb Blood Flow Metab 33:10(1564-73)2013 Oct

23814062. Yu J, Deliu E, Zhang XQ, Hoffman NE, Carter RL, Grisanti LA, Brailoiu GC, Madesh M, Cheung JY, Force T, Abood ME, Koch WJ, Tilley DG, Brailoiu E, Differential activation of cultured neonatal cardiomyocytes by plasmalemmal versus intracellular G protein-coupled receptor 55. J Biol Chem 288:31(22481-92)2013 Aug 2

23805205. Fan Q, Chen M, Zuo L, Shang X, Huang MZ, Ciccarelli M, Raake P, Brinks H, Chuprun KJ, Dorn GW 2nd, Koch WJ, Gao E, Myocardial Ablation of G Protein-Coupled Receptor Kinase 2 (GRK2) Decreases Ischemia/Reperfusion Injury through an Anti-Intrinsic Apoptotic Pathway. PLoS One 8:6(e66234)2013

23795642. Brailoiu GC, Deliu E, Tica AA, Rabinowitz JE, Tilley DG, Benamar K, Koch WJ, Brailoiu E, Nesfatin-1 activates cardiac vagal neurons of nucleus ambiguus and elicits bradycardia in conscious rats. J Neurochem 126:6(739-48)2013 Sep

23713738. Starke RM, Chalouhi N, Ali MS, Jabbour PM, Tjoumakaris SI, Gonzalez LF, Rosenwasser RH, Koch WJ, Dumont AS, The role of oxidative stress in cerebral aneurysm formation and rupture. Curr Neurovasc Res 10:3(247-55)2013 Aug

23472081. Gold JI, Martini JS, Hullmann J, Gao E, Chuprun JK, Lee L, Tilley DG, Rabinowitz JE, Bossuyt J, Bers DM, Koch WJ, Nuclear translocation of cardiac G protein-Coupled Receptor kinase 5 downstream of select Gq-activating hypertrophic ligands is a calmodulin-dependent process. PLoS One 8:3(e57324)2013

23465561. Wang Y, Zhao J, Zhang Y, Lau WB, Jiao LY, Liu B, Yuan Y, Wang X, Tao L, Gao E, Koch WJ, Ma XL, Differential regulation of TNF receptor 1 and receptor 2 in adiponectin expression following myocardial ischemia. Int J Cardiol 168:3(2201-6)2013 Oct 3

23460259. Wei Z, Hurtt R, Gu T, Bodzin AS, Koch WJ, Doria C, GRK2 negatively regulates IGF-1R signaling pathway and cyclins' expression in HepG2 cells. J Cell Physiol 228:9(1897-901)2013 Sep

23376831. Miller BA, Wang J, Hirschler-Laszkiewicz I, Gao E, Song J, Zhang XQ, Koch WJ, Madesh M, Mallilankaraman K, Gu T, Chen SJ, Keefer K, Conrad K, Feldman AM, Cheung JY, The second member of transient receptor potential-melastatin channel family protects hearts from ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 304:7(H1010-22)2013 Apr 1

23360826. Lau WB, Zhang Y, Zhao J, Liu B, Wang X, Yuan Y, Christopher TA, Lopez B, Gao E, Koch WJ, Ma XL, Wang Y, Lymphotoxin-a is a novel adiponectin expression suppressor following myocardial ischemia/reperfusion. Am J Physiol Endocrinol Metab 304:6(E661-7)2013 Mar 15

23348743. Gandhirajan RK, Meng S, Chandramoorthy HC, Mallilankaraman K, Mancarella S, Gao H, Razmpour R, Yang XF, Houser SR, Chen J, Koch WJ, Wang H, Soboloff J, Gill DL, Madesh M, Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation. J Clin Invest 123:2(887-902)2013 Feb 1

23316103. Chalouhi N, Ali MS, Starke RM, Jabbour PM, Tjoumakaris SI, Gonzalez LF, Rosenwasser RH, Koch WJ, Dumont AS, Cigarette smoke and inflammation: role in cerebral aneurysm formation and rupture. Mediators Inflamm 2012:(271582)2012

23273595. Wang J, Gao E, Chan TO, Zhang XQ, Song J, Shang X, Koch WJ, Feldman AM, Cheung JY, Induced overexpression of Na(+)/Ca(2+) exchanger does not aggravate myocardial dysfunction induced by transverse aortic constriction. J Card Fail 19:1(60-70)2013 Jan

23224879. Cheung JY, Zhang XQ, Song J, Gao E, Chan TO, Rabinowitz JE, Koch WJ, Feldman AM, Wang J, Coordinated regulation of cardiac Na(+)/Ca (2+) exchanger and Na (+)-K (+)-ATPase by phospholemman (FXYD1). Adv Exp Med Biol 961:(175-90)2013

23212557. Su H, Yuan Y, Wang XM, Lau WB, Wang Y, Wang X, Gao E, Koch WJ, Ma XL, Inhibition of CTRP9, a novel and cardiac-abundantly expressed cell survival molecule, by TNFa-initiated oxidative signaling contributes to exacerbated cardiac injury in diabetic mice. Basic Res Cardiol 108:1(315)2013 Jan

23086942. Deliu E, Brailoiu GC, Mallilankaraman K, Wang H, Madesh M, Undieh AS, Koch WJ, Brailoiu E, Intracellular endothelin type B receptor-driven Ca2+ signal elicits nitric oxide production in endothelial cells. J Biol Chem 287:49(41023-31)2012 Nov 30

22859683. Gold JI, Gao E, Shang X, Premont RT, Koch WJ, Determining the absolute requirement of G protein-coupled receptor kinase 5 for pathological cardiac hypertrophy: short communication. Circ Res 111:8(1048-53)2012 Sep 28

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