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Steven R. Houser, PhD, FAHA

Chairperson, Department of Physiology

Director, Cardiovascular Research Center

Laura H. Carnell Professor of Physiology

Professor, Medicine

Telephone:  215-707-3278

Fax:  215-707-0170

Office: MERB 1041

Email: srhouser@temple.edu

Department of Physiology

Cardiovascular Research Center

BA, Biology and Chemistry

Eastern College 

 

PhD, Physiology

Temple University School of Medicine

 

Postdoctoral Fellowship, Cardiology

Temple University School of Medicine

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The research in the Houser laboratory is focused on those processes that maintain the electrical and contractile properties of the normal heart and the defects in these processes that lead to electrical instability (arrhythmias and sudden death) and poor cardiac pump performance congestive heart failure). We are currently continuing our studies of the determinants of cellular electrical and mechanical defects in diseased cardiac myocytes. In addition, we are exploring the idea that a major factor that determines the overall state of cardiac myocyte function is a balance between new myocyte formation (cardiac regeneration) and programmed myocyte death (apoptosis).

Our cell physiology studies are exploring the idea that activation of Ca2+ dependent signaling pathways (mainly through CAMKII) regulate Ca2+ handling proteins in diseased myocytes. We have developed techniques in live cells to track Ca2+ dependent activation of NFAT and are characterizing the associated alterations in cell function. These studies are being performed in collaboration with Dr. Jeffrey Molkentin at the University of Cincinnati. The second and third areas of new research are centered on the new idea that there is myocyte turnover in the adult heart. Therefore, we are studying the factors that regulate cell death (mainly through apoptosis, with Dr. Richard Kitsis) and new myocyte formation (via cardiac progenitor cells, with Drs Annarosa Leri and Piero Anversa). We have identified cardiac stem/progenitor cells in feline and human hearts and plan for a rapid expansion of this novel (and controversial) area. We will specifically explore the hypothesis that hypertrophy in response to pressure overload involves new myocyte formation in addition to enlargement of terminally differentiated myocytes. Our newest data shows that expression of T-type Ca2+ channels is linked to differentiation of cardiac stem cells into new cardiac myocytes. Ca2+ influx through these channels also appears to be linked to proliferation of new myocytes.

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

23609274. Taghavi S, Jayarajan SN, Khoche S, Duran JM, Cruz-Schiavone GE, Milner RE, Holt-Bright L, Gaughan JP, Rappold JF, Sjoholm LO, Dujon J, Pathak A, Santora TA, Houser SR, Goldberg AJ, Examining prehospital intubation for penetrating trauma in a swine hemorrhagic shock model. J Trauma Acute Care Surg 74:5(1246-51)2013 May

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

23159931. Mancarella S, Potireddy S, Wang Y, Gao H, Gandhirajan RK, Autieri M, Scalia R, Cheng Z, Wang H, Madesh M, Houser SR, Gill DL, Targeted STIM deletion impairs calcium homeostasis, NFAT activation, and growth of smooth muscle. FASEB J 27:3(893-906)2013 Mar

23067355. Duran JM, Taghavi S, Berretta RM, Makarewich CA, Sharp Iii T, Starosta T, Udeshi F, George JC, Kubo H, Houser SR, A characterization and targeting of the infarct border zone in a Swine model of myocardial infarction. Clin Transl Sci 5:5(416-21)2012 Oct

22921230. Gao H, Wang F, Wang W, Makarewich CA, Zhang H, Kubo H, Berretta RM, Barr LA, Molkentin JD, Houser SR, Ca(2+) influx through L-type Ca(2+) channels and transient receptor potential channels activates pathological hypertrophy signaling. J Mol Cell Cardiol 53:5(657-67)2012 Nov

22846936. Taghavi S, Duran JM, Jayarajan S, Cruz-Schiavone GE, Milner RE, Gaughan JP, Sjoholm LO, Pathak A, Santora TA, Houser SR, Goldberg AJ, Still making the case against prehospital intubation: a rat hemorrhagic shock model. J Trauma Acute Care Surg 73:2(332-7; discussion 337)2012 Aug

22628578. Zhang D, Fang P, Jiang X, Nelson J, Moore JK, Kruger WD, Berretta RM, Houser SR, Yang X, Wang H, Severe hyperhomocysteinemia promotes bone marrow-derived and resident inflammatory monocyte differentiation and atherosclerosis in LDLr/CBS-deficient mice. Circ Res 111:1(37-49)2012 Jun 22

22611476. Taghavi S, Duran JM, Berretta RM, Makarewich CA, Udeshi F, Sharp TE, Kubo H, Houser SR, George JC, Validation of transcatheter left ventricular electromechanical mapping for assessment of cardiac function and targeted transendocardial injection in a porcine ischemia-reperfusion model. Am J Transl Res 4:2(240-6)2012

22609523. Seqqat R, Guo X, Rafiq K, Kolpakov MA, Guo J, Koch WJ, Houser SR, Dell'italia LJ, Sabri A, Beta1-adrenergic receptors promote focal adhesion signaling downregulation and myocyte apoptosis in acute volume overload. J Mol Cell Cardiol 53:2(240-9)2012 Aug

22302787. Makarewich CA, Correll RN, Gao H, Zhang H, Yang B, Berretta RM, Rizzo V, Molkentin JD, Houser SR, A caveolae-targeted L-type Ca²+ channel antagonist inhibits hypertrophic signaling without reducing cardiac contractility. Circ Res 110:5(669-74)2012 Mar 2

22302785. Zhang H, Makarewich CA, Kubo H, Wang W, Duran JM, Li Y, Berretta RM, Koch WJ, Chen X, Gao E, Valdivia HH, Houser SR, Hyperphosphorylation of the cardiac ryanodine receptor at serine 2808 is not involved in cardiac dysfunction after myocardial infarction. Circ Res 110:6(831-40)2012 Mar 16

22203672. Rafiq K, Guo J, Vlasenko L, Guo X, Kolpakov MA, Sanjay A, Houser SR, Sabri A, c-Cbl ubiquitin ligase regulates focal adhesion protein turnover and myofibril degeneration induced by neutrophil protease cathepsin G. J Biol Chem 287:8(5327-39)2012 Feb 17

21746883. Irrinki KM, Mallilankaraman K, Thapa RJ, Chandramoorthy HC, Smith FJ, Jog NR, Gandhirajan RK, Kelsen SG, Houser SR, May MJ, Balachandran S, Madesh M, Requirement of FADD, NEMO, and BAX/BAK for aberrant mitochondrial function in tumor necrosis factor alpha-induced necrosis. Mol Cell Biol 31:18(3745-58)2011 Sep

21454756. Angert D, Berretta RM, Kubo H, Zhang H, Chen X, Wang W, Ogorek B, Barbe M, Houser SR, Repair of the injured adult heart involves new myocytes potentially derived from resident cardiac stem cells. Circ Res 108:10(1226-37)2011 May 13

21111744. Chen X, Nakayama H, Zhang X, Ai X, Harris DM, Tang M, Zhang H, Szeto C, Stockbower K, Berretta RM, Eckhart AD, Koch WJ, Molkentin JD, Houser SR, Calcium influx through Cav1.2 is a proximal signal for pathological cardiomyocyte hypertrophy. J Mol Cell Cardiol 50:3(460-70)2011 Mar

20671241. Zhang H, Chen X, Gao E, MacDonnell SM, Wang W, Kolpakov M, Nakayama H, Zhang X, Jaleel N, Harris DM, Li Y, Tang M, Berretta R, Leri A, Kajstura J, Sabri A, Koch WJ, Molkentin JD, Houser SR, Increasing cardiac contractility after myocardial infarction exacerbates cardiac injury and pump dysfunction. Circ Res 107:6(800-9)2010 Sep 17

19716828. Kolpakov MA, Seqqat R, Rafiq K, Xi H, Margulies KB, Libonati JR, Powel P, Houser SR, Dell'italia LJ, Sabri A, Pleiotropic effects of neutrophils on myocyte apoptosis and left ventricular remodeling during early volume overload. J Mol Cell Cardiol 47:5(634-45)2009 Nov

19627664. Angert D, Houser SR, Stem cell therapy for heart failure. Curr Treat Options Cardiovasc Med 11:4(316-27)2009 Aug

19608982. MacDonnell SM, Weisser-Thomas J, Kubo H, Hanscome M, Liu Q, Jaleel N, Berretta R, Chen X, Brown JH, Sabri AK, Molkentin JD, Houser SR, CaMKII negatively regulates calcineurin-NFAT signaling in cardiac myocytes. Circ Res 105:4(316-25)2009 Aug 14

20443864. Kubo H, Berretta RM, Jaleel N, Angert D, Houser SR, c-Kit+ bone marrow stem cells differentiate into functional cardiac myocytes. Clin Transl Sci 2:1(26-32)2009 Feb

19065545. Molina EJ, Palma J, Gupta D, Torres D, Gaughan JP, Houser S, Macha M, Reverse remodeling is associated with changes in extracellular matrix proteases and tissue inhibitors after mesenchymal stem cell (MSC) treatment of pressure overload hypertrophy. J Tissue Eng Regen Med 3:2(85-91)2009 Feb

18993028. Molina EJ, Palma J, Gupta D, Gaughan JP, Houser S, Macha M, Right ventricular effects of intracoronary delivery of mesenchymal stem cells (MSC) in an animal model of pressure overload heart failure. Biomed Pharmacother 63:10(767-72)2009 Dec

18855260. Kolwicz SC, MacDonnell SM, Kendrick ZV, Houser SR, Libonati JR, Voluntary wheel running and pacing-induced dysfunction in hypertension. Clin Exp Hypertens 30:7(565-73)2008 Oct

18832749. Jaleel N, Nakayama H, Chen X, Kubo H, MacDonnell S, Zhang H, Berretta R, Robbins J, Cribbs L, Molkentin JD, Houser SR, Ca2+ influx through T- and L-type Ca2+ channels have different effects on myocyte contractility and induce unique cardiac phenotypes. Circ Res 103:10(1109-19)2008 Nov 7

18755480. Molina EJ, Gupta D, Palma J, Torres D, Gaughan JP, Houser S, Macha M, Novel experimental model of pressure overload hypertrophy in rats. J Surg Res 153:2(287-94)2009 May 15

18645055. Kubo H, Jaleel N, Kumarapeli A, Berretta RM, Bratinov G, Shan X, Wang H, Houser SR, Margulies KB, Increased cardiac myocyte progenitors in failing human hearts. Circulation 118:6(649-57)2008 Aug 5

18577756. Houser SR, Molkentin JD, Does contractile Ca2+ control calcineurin-NFAT signaling and pathological hypertrophy in cardiac myocytes? Sci Signal 1:25(pe31)2008 Jun 24

18388322. MacDonnell SM, García-Rivas G, Scherman JA, Kubo H, Chen X, Valdivia H, Houser SR, Adrenergic regulation of cardiac contractility does not involve phosphorylation of the cardiac ryanodine receptor at serine 2808. Circ Res 102:8(e65-72)2008 Apr 25

18359894. Chen X, Zhang X, Harris DM, Piacentino V 3rd, Berretta RM, Margulies KB, Houser SR, Reduced effects of BAY K 8644 on L-type Ca2+ current in failing human cardiac myocytes are related to abnormal adrenergic regulation. Am J Physiol Heart Circ Physiol 294:5(H2257-67)2008 May

18262563. Gupta D, Palma J, Molina E, Gaughan JP, Long W, Houser S, Macha M, Improved exercise capacity and reduced systemic inflammation after adenoviral-mediated SERCA-2a gene transfer. J Surg Res 145:2(257-65)2008 Apr

18242254. Molina EJ, Palma J, Gupta D, Torres D, Gaughan JP, Houser S, Macha M, Improvement in hemodynamic performance, exercise capacity, inflammatory profile, and left ventricular reverse remodeling after intracoronary delivery of mesenchymal stem cells in an experimental model of pressure overload hypertrophy. J Thorac Cardiovasc Surg 135:2(292-9, 299.e1)2008 Feb

17931654. Quaile MP, Rossman EI, Berretta RM, Bratinov G, Kubo H, Houser SR, Margulies KB, Reduced sarcoplasmic reticulum Ca(2+) load mediates impaired contractile reserve in right ventricular pressure overload. J Mol Cell Cardiol 43:5(552-63)2007 Nov

17827263. MacDonnell SM, Kubo H, Harris DM, Chen X, Berretta R, Barbe MF, Kolwicz S, Reger PO, Eckhart A, Renna BF, Koch WJ, Houser SR, Libonati JR, Calcineurin inhibition normalizes beta-adrenergic responsiveness in the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 293:5(H3122-9)2007 Nov

17594913. McGinley JC, Berretta RM, Chaudhary K, Rossman E, Bratinov GD, Gaughan JP, Houser S, Margulies KB, Impaired contractile reserve in severe mitral valve regurgitation with a preserved ejection fraction. Eur J Heart Fail 9:9(857-64)2007 Sep

17431084. Renna BF, MacDonnell SM, Reger PO, Crabbe DL, Houser SR, Libonati JR, Relative systolic dysfunction in female spontaneously hypertensive rat myocardium. J Appl Physiol 103:1(353-8)2007 Jul

17272809. Chen X, Wilson RM, Kubo H, Berretta RM, Harris DM, Zhang X, Jaleel N, MacDonnell SM, Bearzi C, Tillmanns J, Trofimova I, Hosoda T, Mosna F, Cribbs L, Leri A, Kajstura J, Anversa P, Houser SR, Adolescent feline heart contains a population of small, proliferative ventricular myocytes with immature physiological properties. Circ Res 100:4(536-44)2007 Mar 2

17012360. Mills GD, Harris DM, Chen X, Houser SR, Intracellular sodium determines frequency-dependent alterations in contractility in hypertrophied feline ventricular myocytes. Am J Physiol Heart Circ Physiol 292:2(H1129-38)2007 Feb

17008460. Petre RE, Quaile MP, Rossman EI, Ratcliffe SJ, Bailey BA, Houser SR, Margulies KB, Sex-based differences in myocardial contractile reserve. Am J Physiol Regul Integr Comp Physiol 292:2(R810-8)2007 Feb

16772527. Mills GD, Kubo H, Harris DM, Berretta RM, Piacentino V 3rd, Houser SR, Phosphorylation of phospholamban at threonine-17 reduces cardiac adrenergic contractile responsiveness in chronic pressure overload-induced hypertrophy. Am J Physiol Heart Circ Physiol 291:1(H61-70)2006 Jul

16672836. Renna BF, Kubo H, MacDonnell SM, Crabbe DL, Reger PO, Houser SR, Libonati JR, Enhanced acidotic myocardial Ca2+ responsiveness with training in hypertension. Med Sci Sports Exerc 38:5(847-55)2006 May

16414453. Litvin J, Blagg A, Mu A, Matiwala S, Montgomery M, Berretta R, Houser S, Margulies K, Periostin and periostin-like factor in the human heart: possible therapeutic targets. Cardiovasc Pathol 15:1(24-32)2006 Jan-Feb

16399650. Petre RE, Quaile MP, Wendt K, Houser SR, Wald J, Goldman BI, Margulies KB, Regionally heterogeneous tissue mechanics in cardiac amyloidosis. Amyloid 12:4(246-50)2005 Dec

16210547. Chen X, Zhang X, Kubo H, Harris DM, Mills GD, Moyer J, Berretta R, Potts ST, Marsh JD, Houser SR, Ca2+ influx-induced sarcoplasmic reticulum Ca2+ overload causes mitochondrial-dependent apoptosis in ventricular myocytes. Circ Res 97:10(1009-17)2005 Nov 11

16037397. Libonati JR, Kendrick ZV, Houser SR, Sprint training improves postischemic, left ventricular diastolic performance. J Appl Physiol 99:6(2121-7)2005 Dec

15967848. MacDonnell SM, Kubo H, Crabbe DL, Renna BF, Reger PO, Mohara J, Smithwick LA, Koch WJ, Houser SR, Libonati JR, Improved myocardial beta-adrenergic responsiveness and signaling with exercise training in hypertension. Circulation 111:25(3420-8)2005 Jun 28

15948089. Weisser-Thomas J, Kubo H, Hefner CA, Gaughan JP, McGowan BS, Ross R, Meyer M, Dillmann W, Houser SR, The Na+/Ca2+ exchanger/SR Ca2+ ATPase transport capacity regulates the contractility of normal and hypertrophied feline ventricular myocytes. J Card Fail 11:5(380-7)2005 Jun

15705962. Harris DM, Mills GD, Chen X, Kubo H, Berretta RM, Votaw VS, Santana LF, Houser SR, Alterations in early action potential repolarization causes localized failure of sarcoplasmic reticulum Ca2+ release. Circ Res 96:5(543-50)2005 Mar 18

15550574. Jung AS, Quaile MP, Mills GD, Bednarik DP, Houser SR, Margulies KB, Pharmacological effects of ATI22-107 [2-(2-{2-[2-chloro-4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-acetylamino}-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester)], a novel dual pharmacophore, on myocyte calcium cycling and contractility. J Pharmacol Exp Ther 312:2(517-24)2005 Feb

15312868. Chaudhary KW, Rossman EI, Piacentino V 3rd, Kenessey A, Weber C, Gaughan JP, Ojamaa K, Klein I, Bers DM, Houser SR, Margulies KB, Altered myocardial Ca2+ cycling after left ventricular assist device support in the failing human heart. J Am Coll Cardiol 44:4(837-45)2004 Aug 18

14734045. Rossman EI, Petre RE, Chaudhary KW, Piacentino V 3rd, Janssen PM, Gaughan JP, Houser SR, Margulies KB, Abnormal frequency-dependent responses represent the pathophysiologic signature of contractile failure in human myocardium. J Mol Cell Cardiol 36:1(33-42)2004 Jan

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Postdoctoral Fellows

Lab phone number 215-707-3275

Hui Gao                                    hui.gau@temple.edu

Hajime Kubo, PhD                 hajime.kubo@temple.edu

Hongyu Zhang                        hongyu.zhang@temple.edu

                                                                                                                                                      

Graduate Students

Larry Barr                                  larry.barr@temple.edu

Jason Duran                            jason.duran@temple.edu

Catherine Makarewich           cat.makarewish@gmail.com

Thomas Sharp                        tuc72715@temple.edu

Fang Wang                               tub50225@temple.edu

Hongyu Zhang                         hongyu.zhang@temple.edu

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Remus Berretta

Lab Manager

T:  215-707-6501

F:  215-707-0170

Email address:  remus.berretta@temple.edu

Tim Starosta

Laboratory Assistant

Email address: tua92387@temple.edu

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