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Thomas L. Force, MD

 

Thomas L. Force, MD

 

Professor, Medicine

Professor, Center for Translational Medicine

Clinical Director, Center for Translational Medicine

Telephone:  215-707-9829

Fax: 215-707-9890

Email: thomas.force@temple.edu

 

 

Department of Medicine, Section of Cardiology

Center for Translational Medicine

 

Educational Background:

 

Undergraduate degree: Harvard College, Cambridge, MA, 1973

 

MD, Harvard Medical School, Boston, MA, 1978

 

Internship/Residency, Internal Medicine, University of Vermont, Burlington, VT, 1978-1981

 

Clinical Fellowship, Brigham & Women's Hospital, West Roxbury VA Medical Center, Boston, MA, 1981-1983

 

Research Fellowship, Brigham & Women's Hospital, Boston, MA, 1983-1984

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BOARD CERTIFICATIONS:

 

  • Internal Medicine
  • Cardiovascular Diseases

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PROFESSIONAL AFFILIATIONS:

 

  • President Elect, Heart Failure Society of America
  • Fellow, American Heart Association
  • International Society for Heart Research
  • European Society of Cardiology

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Research Interests:

 

Dr. Force’s lab focuses on the regulation of normal and stress-induced cardiomyocyte hypertrophy. Specifically, we study the signal transduction pathways that regulate growth responses, focusing on protein kinase cascades. Most recently, we have studied the role of glycogen synthase kinase-3beta, which is a potent negative regulator of growth, and its downstream targets, which include beta-catenin and its co-factors, the Tcf family of transcription factors, and the family of nuclear factors of activated T cells (NF-ATs), in hypertrophic growth. In addition, we study signaling mechanisms that regulate the response of the cell to ischemic injury. Making use of novel small molecule inhibitors, we have recently identified a novel mechanism by which the JNK family of stress-activated protein kinases regulate activity of the pro-survival kinase, Akt/PKB, and, via this mechanism, cardiomyocyte survival following ischemia/reperfusion.

 

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PUBMED PUBLICATIONS :


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

24932213. Ewer M, Gianni L, Pane F, Sandri MT, Steiner RK, Wojnowski L, Yeh ET, Carver JR, Lipshultz SE, Minotti G, Armstrong GT, Cardinale D, Colan SD, Darby SC, Force TL, Kremer LC, Lenihan DJ, Sallan SE, Sawyer DB, Suter TM, Swain SM, van Leeuwen FE, Report on the international colloquium on cardio-oncology (rome, 12-14 march 2014). Ecancermedicalscience 8:(433)2014

24931551. Barr LA, Makarewich CA, Berretta RM, Gao H, Troupes CD, Woitek F, Recchia F, Kubo H, Force T, Houser SR, Imatinib Activates Pathological Hypertrophy by Altering Myocyte Calcium Regulation. Clin Transl Sci :()2014 Jun 16

24899689. Lal H, Ahmad F, Zhou J, Yu JE, Vagnozzi RJ, Guo Y, Yu D, Tsai EJ, Woodgett J, Gao E, Force T, Cardiac Fibroblast GSK-3ß Regulates Ventricular Remodeling and Dysfunction in Ischemic Heart. Circulation :()2014 Jun 4

24899531. Lal H, Ahmad F, Parikh S, Force T, Troponin I-interacting protein kinase. Circ J 78:7(1514-9)2014 Jun 25

24718482. Duran JM, Makarewich CA, Trappanese D, Gross P, Husain S, Dunn J, Lal H, Sharp TE, Starosta T, Vagnozzi RJ, Berretta RM, Barbe M, Yu D, Gao E, Kubo H, Force T, Houser SR, Sorafenib cardiotoxicity increases mortality after myocardial infarction. Circ Res 114:11(1700-12)2014 May 23

24332854. Hoffman NE, Chandramoorthy HC, Shamugapriya S, Zhang X, Rajan S, Mallilankaraman K, Gandhirajan RK, Vagnozzi RJ, Ferrer LM, Sreekrishnanilayam K, Natarajaseenivasan K, Vallem S, Force T, Choi ET, Cheung JY, Madesh M, MICU1 motifs define mitochondrial calcium uniporter binding and activity. Cell Rep 5:6(1576-88)2013 Dec 26

24132636. Vagnozzi RJ, Gatto GJ Jr, Kallander LS, Hoffman NE, Mallilankaraman K, Ballard VL, Lawhorn BG, Stoy P, Philp J, Graves AP, Naito Y, Lepore JJ, Gao E, Madesh M, Force T, Inhibition of the cardiomyocyte-specific kinase TNNI3K limits oxidative stress, injury, and adverse remodeling in the ischemic heart. Sci Transl Med 5:207(207ra141)2013 Oct 16

23990596. Springer J, Tschirner A, Haghikia A, von Haehling S, Lal H, Grzesiak A, Kaschina E, Palus S, Pötsch M, von Websky K, Hocher B, Latouche C, Jaisser F, Morawietz L, Coats AJ, Beadle J, Argiles JM, Thum T, Földes G, Doehner W, Hilfiker-Kleiner D, Force T, Anker SD, Prevention of liver cancer cachexia-induced cardiac wasting and heart failure. Eur Heart J 35:14(932-41)2014 Apr

23989717. Ky B, Vejpongsa P, Yeh ET, Force T, Moslehi JJ, Emerging paradigms in cardiomyopathies associated with cancer therapies. Circ Res 113:6(754-64)2013 Aug 30

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

23804600. Zhou J, Force T, Focusing the spotlight on GSK-3 in aging. Aging (Albany NY) 5:6(388-9)2013 Jun

23757311. Force T, Wang Y, Mechanism-based engineering against anthracycline cardiotoxicity. Circulation 128:2(98-100)2013 Jul 9

23549082. Zhou J, Freeman TA, Ahmad F, Shang X, Mangano E, Gao E, Farber J, Wang Y, Ma XL, Woodgett J, Vagnozzi RJ, Lal H, Force T, GSK-3a is a central regulator of age-related pathologies in mice. J Clin Invest 123:4(1821-32)2013 Apr 1

23328609. Lal H, Kolaja KL, Force T, Cancer genetics and the cardiotoxicity of the therapeutics. J Am Coll Cardiol 61:3(267-74)2013 Jan 22

22751436. McClendon AK, Dean JL, Rivadeneira DB, Yu JE, Reed CA, Gao E, Farber JL, Force T, Koch WJ, Knudsen ES, CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy. Cell Cycle 11:14(2747-55)2012 Jul 15

22451582. Force T, Double-edged sword of the new cancer therapeutics. Circulation 125:17(2057-8)2012 May 1

22305831. Steingart RM, Bakris GL, Chen HX, Chen MH, Force T, Ivy SP, Leier CV, Liu G, Lenihan D, Lindenfeld J, Maitland ML, Remick SC, Tang WH, Management of cardiac toxicity in patients receiving vascular endothelial growth factor signaling pathway inhibitors. Am Heart J 163:2(156-63)2012 Feb

22300775. Greenberg BH, Anand IS, Burnett JC Jr, Chin J, Dracup KA, Feldman AM, Force T, Francis GS, Houser SR, Hunt SA, Konstam MA, Lindenfeld J, Mann DL, Mehra MR, Paul SC, Piano MR, Ross HJ, Sabbah HN, Starling RC, Udelson JE, Yancy CW, Zile MR, Massie BM, The Heart Failure Society of America in 2020: a vision for the future. J Card Fail 18:2(90-3)2012 Feb

24839450. Vagnozzi RJ, Hoffman NE, Elrod JW, Madesh M, Force T, Protein Kinase Signaling at the Crossroads of Myocyte Life and Death in Ischemic Heart Disease. Drug Discov Today Ther Strateg 9:4(e173-e182)2012

22086876. Lal H, Zhou J, Ahmad F, Zaka R, Vagnozzi RJ, Decaul M, Woodgett J, Gao E, Force T, Glycogen synthase kinase-3a limits ischemic injury, cardiac rupture, post-myocardial infarction remodeling and death. Circulation 125:1(65-75)2012 Jan 3

22034491. Oikonomopoulos A, Sereti KI, Conyers F, Bauer M, Liao A, Guan J, Crapps D, Han JK, Dong H, Bayomy AF, Fine GC, Westerman K, Biechele TL, Moon RT, Force T, Liao R, Wnt signaling exerts an antiproliferative effect on adult cardiac progenitor cells through IGFBP3. Circ Res 109:12(1363-74)2011 Dec 9

22001647. Hernández G, Lal H, Fidalgo M, Guerrero A, Zalvide J, Force T, Pombo CM, A novel cardioprotective p38-MAPK/mTOR pathway. Exp Cell Res 317:20(2938-49)2011 Dec 10

21998323. Cheng H, Kari G, Dicker AP, Rodeck U, Koch WJ, Force T, A novel preclinical strategy for identifying cardiotoxic kinase inhibitors and mechanisms of cardiotoxicity. Circ Res 109:12(1401-9)2011 Dec 9

21884509. Kerkelä R, Boucher M, Zaka R, Gao E, Harris D, Piuhola J, Song J, Serpi R, Woulfe KC, Cheung JY, O'Leary E, Bonventre JV, Force T, Cytosolic phospholipase A(2)a protects against ischemia/reperfusion injury in the heart. Clin Transl Sci 4:4(236-42)2011 Aug

21720463. Khakoo AY, Liu PP, Force T, Lopez-Berestein G, Jones LW, Schneider J, Hill J, Cardiotoxicity due to cancer therapy. Tex Heart Inst J 38:3(253-6)2011

21283106. Force T, Kolaja KL, Cardiotoxicity of kinase inhibitors: the prediction and translation of preclinical models to clinical outcomes. Nat Rev Drug Discov 10:2(111-26)2011 Feb

21278838. Marber MS, Molkentin JD, Force T, Developing small molecules to inhibit kinases unkind to the heart: p38 MAPK as a case in point. Drug Discov Today Dis Mech 7:2(e123-e127)2010 Summer

21169385. Eschenhagen T, Force T, Ewer MS, de Keulenaer GW, Suter TM, Anker SD, Avkiran M, de Azambuja E, Balligand JL, Brutsaert DL, Condorelli G, Hansen A, Heymans S, Hill JA, Hirsch E, Hilfiker-Kleiner D, Janssens S, de Jong S, Neubauer G, Pieske B, Ponikowski P, Pirmohamed M, Rauchhaus M, Sawyer D, Sugden PH, Wojta J, Zannad F, Shah AM, Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 13:1(1-10)2011 Jan

21163265. Cheng H, Woodgett J, Maamari M, Force T, Targeting GSK-3 family members in the heart: a very sharp double-edged sword. J Mol Cell Cardiol 51:4(607-13)2011 Oct

20959622. Rose BA, Force T, Wang Y, Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale. Physiol Rev 90:4(1507-46)2010 Oct

20890047. Elrod JW, Wong R, Mishra S, Vagnozzi RJ, Sakthievel B, Goonasekera SA, Karch J, Gabel S, Farber J, Force T, Brown JH, Murphy E, Molkentin JD, Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice. J Clin Invest 120:10(3680-7)2010 Oct

20837938. Force T, Bonow RO, Houser SR, Solaro RJ, Hershberger RE, Adhikari B, Anderson ME, Boineau R, Byrne BJ, Cappola TP, Kalluri R, LeWinter MM, Maron MS, Molkentin JD, Ommen SR, Regnier M, Tang WH, Tian R, Konstam MA, Maron BJ, Seidman CE, Research priorities in hypertrophic cardiomyopathy: report of a Working Group of the National Heart, Lung, and Blood Institute. Circulation 122:11(1130-3)2010 Sep 14

20728698. Cheng H, Force T, Why do kinase inhibitors cause cardiotoxicity and what can be done about it? Prog Cardiovasc Dis 53:2(114-20)2010 Sep-Oct

20718819. Feldman AM, Force TL, Whellan DJ, Bray PF, Cheung JY, Koch WJ, Advancing the research mission in an academic department: the creation of a center for translational medicine. Clin Transl Sci 3:4(178-81)2010 Aug

20516643. Zhou J, Lal H, Chen X, Shang X, Song J, Li Y, Kerkela R, Doble BW, MacAulay K, DeCaul M, Koch WJ, Farber J, Woodgett J, Gao E, Force T, GSK-3alpha directly regulates beta-adrenergic signaling and the response of the heart to hemodynamic stress in mice. J Clin Invest 120:7(2280-91)2010 Jul

20360256. Woulfe KC, Gao E, Lal H, Harris D, Fan Q, Vagnozzi R, DeCaul M, Shang X, Patel S, Woodgett JR, Force T, Zhou J, Glycogen synthase kinase-3beta regulates post-myocardial infarction remodeling and stress-induced cardiomyocyte proliferation in vivo. Circ Res 106:10(1635-45)2010 May 28

20332113. Fidalgo M, Fraile M, Pires A, Force T, Pombo C, Zalvide J, CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation. J Cell Sci 123:Pt 8(1274-84)2010 Apr 15

20056943. Cheng H, Force T, Molecular mechanisms of cardiovascular toxicity of targeted cancer therapeutics. Circ Res 106:1(21-34)2010 Jan 8

20056942. Force T, Introduction to cardiotoxicity review series. Circ Res 106:1(19-20)2010 Jan 8

19451227. Zhou J, Shao Z, Kerkela R, Ichijo H, Muslin AJ, Pombo C, Force T, Serine 58 of 14-3-3zeta is a molecular switch regulating ASK1 and oxidant stress-induced cell death. Mol Cell Biol 29:15(4167-76)2009 Aug

20376335. Kerkela R, Woulfe KC, Durand JB, Vagnozzi R, Kramer D, Chu TF, Beahm C, Chen MH, Force T, Sunitinib-induced cardiotoxicity is mediated by off-target inhibition of AMP-activated protein kinase. Clin Transl Sci 2:1(15-25)2009 Feb

19064989. Force T, Woodgett JR, Unique and overlapping functions of GSK-3 isoforms in cell differentiation and proliferation and cardiovascular development. J Biol Chem 284:15(9643-7)2009 Apr 10

18830417. Kerkela R, Kockeritz L, Macaulay K, Zhou J, Doble BW, Beahm C, Greytak S, Woulfe K, Trivedi CM, Woodgett JR, Epstein JA, Force T, Huggins GS, Deletion of GSK-3beta in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation. J Clin Invest 118:11(3609-18)2008 Nov

18617014. Force T, Kerkelä R, Cardiotoxicity of the new cancer therapeutics--mechanisms of, and approaches to, the problem. Drug Discov Today 13:17-18(778-84)2008 Sep

18591451. Chen MH, Kerkelä R, Force T, Mechanisms of cardiac dysfunction associated with tyrosine kinase inhibitor cancer therapeutics. Circulation 118:1(84-95)2008 Jul 1

18381189. Patten RD, Pourati I, Aronovitz MJ, Alsheikh-Ali A, Eder S, Force T, Mendelsohn ME, Karas RH, 17 Beta-estradiol differentially affects left ventricular and cardiomyocyte hypertrophy following myocardial infarction and pressure overload. J Card Fail 14:3(245-53)2008 Apr

18364353. Nogueira E, Fidalgo M, Molnar A, Kyriakis J, Force T, Zalvide J, Pombo CM, SOK1 translocates from the Golgi to the nucleus upon chemical anoxia and induces apoptotic cell death. J Biol Chem 283:23(16248-58)2008 Jun 6

18323842. Force T, The weakness of a big heart. Nat Med 14:3(244-5)2008 Mar

18083403. Chu TF, Rupnick MA, Kerkela R, Dallabrida SM, Zurakowski D, Nguyen L, Woulfe K, Pravda E, Cassiola F, Desai J, George S, Morgan JA, Harris DM, Ismail NS, Chen JH, Schoen FJ, Van den Abbeele AD, Demetri GD, Force T, Chen MH, Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 370:9604(2011-9)2007 Dec 15

18040021. Liao R, Force T, Not all hypertrophy is created equal. Circ Res 101:11(1069-72)2007 Nov 26

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