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FAculty directory
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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
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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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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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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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)
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
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
17666710. Force T, Woulfe K, Koch WJ, Kerkelä R, Molecular scaffolds regulate bidirectional crosstalk between Wnt and classical seven-transmembrane-domain receptor signaling pathways. Sci STKE 2007:397(pe41)2007 Jul 31
17457301. Force T, Krause DS, Van Etten RA, Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer 7:5(332-44)2007 May
17418370. Kerkelä R, Woulfe K, Force T, Glycogen synthase kinase-3beta -- actively inhibiting hypertrophy. Trends Cardiovasc Med 17:3(91-6)2007 Apr
17392727. Feldman AM, Koch WJ, Force TL, Developing strategies to link basic cardiovascular sciences with clinical drug development: another opportunity for translational sciences. Clin Pharmacol Ther 81:6(887-92)2007 Jun
17127342. Pombo CM, Force T, Kyriakis J, Nogueira E, Fidalgo M, Zalvide J, The GCK II and III subfamilies of the STE20 group kinases. Front Biosci 12:(850-9)2007 Jan 1
17116693. Goruppi S, Patten RD, Force T, Kyriakis JM, Helix-loop-helix protein p8, a transcriptional regulator required for cardiomyocyte hypertrophy and cardiac fibroblast matrix metalloprotease induction. Mol Cell Biol 27:3(993-1006)2007 Feb
17035736. Shevtsov SP, Haq S, Force T, Activation of beta-catenin signaling pathways by classical G-protein-coupled receptors: mechanisms and consequences in cycling and non-cycling cells. Cell Cycle 5:20(2295-300)2006 Oct
16875983. Kerkela R, Force T, p38 mitogen-activated protein kinase: a future target for heart failure therapy? J Am Coll Cardiol 48:3(556-8)2006 Aug 1
16862153. Kerkelä R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, Walters B, Shevtsov S, Pesant S, Clubb FJ, Rosenzweig A, Salomon RN, Van Etten RA, Alroy J, Durand JB, Force T, Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 12:8(908-16)2006 Aug
16782890. Xu D, Patten RD, Force T, Kyriakis JM, Gene 33/RALT is induced by hypoxia in cardiomyocytes, where it promotes cell death by suppressing phosphatidylinositol 3-kinase and extracellular signal-regulated kinase survival signaling. Mol Cell Biol 26:13(5043-54)2006 Jul
16738313. Chen X, Shevtsov SP, Hsich E, Cui L, Haq S, Aronovitz M, Kerkelä R, Molkentin JD, Liao R, Salomon RN, Patten R, Force T, The beta-catenin/T-cell factor/lymphocyte enhancer factor signaling pathway is required for normal and stress-induced cardiac hypertrophy. Mol Cell Biol 26:12(4462-73)2006 Jun
16684492. Kerkela R, Force T, Recent insights into cardiac hypertrophy and left ventricular remodeling. Curr Heart Fail Rep 3:1(14-8)2006 Apr
16500577. Massie BM, Force T, The year in heart failure 2005. J Card Fail 12:1(1-9)2006 Feb
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