Washington University - Cardiovascular Division

Anthony J. Muslin, M.D.

Oliver M. Langenberg Distinguished Professor of the Science and Practice of Medicine; Professor of Cell Biology and Physiology; Director, Cardiology Research Fellowship Program; Co-Director, Physician Scientist Training Program (PSTP), Washington University School of Medicine, St. Louis, MO

Contact Information:
Room 9910, Clinical Sciences Research Building (CSRB)
Phone 314-747-3525
Fax 314-747-3545
E-mail: amuslin@wustl.edu

Education and Training:
Yale University, New Haven, Connecticut, B.A. History, 1980
Harvard Medical School, Boston, Massachusetts, M.D., 1984
1984-1987: Intern and Resident in Internal Medicine, Brigham & Women's Hospital, Boston, Massachusetts
1987-1989: Cardiology Fellow, University of California, San Francisco
1989-1992: Cardiology Research Fellow, University of California, San Francisco
1992-1994: Adjunct Assistant Professor of Medicine, University of California, San Francisco
1994-1999: Assistant Professor of Medicine, Washington University School of Medicine, St. Louis , Missouri
1999-2002: Associate Professor of Medicine, Washington University School of Medicine
2001-present: Director, Cardiology Research Fellowship Program
2001-present: Co-Director, Physician Scientist Training Program (PSTP)
2002-2006: Professor of Medicine, Washington University School of Medicine
2002-present: Professor of Cell Biology and Physiology, Washington University School of Medicine
2006-present: Oliver M. Langenberg Distinguished Professor of the Science and Practice
of Medicine

Honors and Awards:
1979: Phi Beta Kappa, Yale University
1980: Graduated magna cum laude, Yale University
1990: Henry Christian Memorial Award, American Federation for Clinical Research
1992: Physician Scientist Award, NHLBI
1999: Dr. Lee B. and Virginia G. Harrison Physician Scholar, Washington University School of Medicine
2000: Established Investigator Award, American Heart Association
2000: Elected Member, American Society for Clinical Investigation (ASCI)
2001: Clinical Scientist Award in Translational Research, Burroughs Wellcome Fund
2004: Elected Member, Association of American Physicians (AAP)
2006: Elected to Fellowship in the American Heart Association (FAHA), Council on Basic Cardiovascular Sciences
2007: Elected Member, Association of University Cardiologists (AUC)

Clinical Expertise:
Cardiovascular Care Unit (CCU)

Selected Publications:
Fantl WJ*, Muslin AJ*,Kikuchi A, Martin JA, MacNicol AM, Gross RW, and Williams LT. Activation of Raf-1 by 14-3-3 proteins. Nature 1994; 371, 612-615 (*co-first authors).

Hu Q, Klippel A, Muslin AJ, Fantl WJ, and Williams, LT. Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase. Science 1995; 268:100-102.

MacNicol AM, Muslin AJ, Howard EL, Kikuchi A, MacNicol MC, and Williams LT. Regulation of Raf-1-dependent signaling during early Xenopus development. Mol. Cell. Biol. 1995; 15:6686-6693.

Muslin AJ, Tanner JW, Allen PM, and Shaw AS. Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell 1996; 84:889-898.

Kawabe T, Muslin AJ, and Korsmeyer SJ. Hox11 interacts with protein phosphatase 2A and disrupts a G2/M checkpoint. Nature 1997; 385, 454-458.

Xing H, Kornfeld K, and Muslin AJ. KSR interacts with 14-3-3 protein and Raf. Current Biology1997; 7:294-300.

Zhang S, Watson N, Zahner J, Blumer KJ, and Muslin AJ. RGS3 and RGS4 are G protein inhibitors in the heart. J. Mol. Cell. Card. 1998; 30:269-276.

Tamirisa P, Blumer KJ, and Muslin AJ. RGS4 inhibits G protein signaling in cardiomyocytes. Circulation 1999; 99: 441-447.

Jacobs D, Glossip D, Xing H, Muslin AJ, and Kornfeld K. Multiple docking sites on substrate recognition proteins form a modular system that mediates recognition by ERK MAP kinase. Genes Dev. 1999; 13:163-175.

Bell B, Xing H, Yan K, Gautam N, and Muslin AJ. KSR-1 binds to G-protein bg subunits and inhibits bg-induced MAP kinase activation. J. Biol. Chem. 1999; 274:7982-7986.

Goyal RK, Lin P, Kanungo J, Payne AS , Muslin AJ, and Longmore GD. Ajuba, a novel LIM protein, interacts with Grb2, augments MAP kinase activity in fibroblasts, and promotes meiotic maturation of Xenopus oocytes in a Grb2- and Ras-dependent manner. Mol. Cell. Biol. 1999; 19:4379-4389.

Zhang S, Xing H, and Muslin AJ. Nuclear localization of PKU-a is regulated by 14-3-3 . J. Biol. Chem.1999; 275:24865-24872.

Rogers J, Tamirisa P, Kovacs A, Weinheimer C, Blumer KJ, Kelly DJ, and Muslin AJ. RGS4 causes increased mortality and reduced cardiac hypertrophy in response to pressure overload. J. Clin. Invest. 1999; 104:567-576.

MacNicol M, Muslin AJ, and MacNicol AM. Disruption of the 14-3-3 Binding Site within the B-Raf Kinase Domain Uncouples Catalytic Activity from PC12 Cell Differentiation. J. Biol. Chem. 2000; 275:3803-3809.

Xing H, Zhang S, Weinheimer C, Kovacs A, and Muslin AJ. 14-3-3 proteins inhibit apoptosis and differentially regulate MAPK cascades. EMBO J. 2000; 19:349-358.

Wu C, Zeng Q, Blumer KJ, and Muslin AJ. RGS proteins inhibit Xwnt-8 in Xenopus embryonic development. Development 2000; 127:2773-2784.

Rogers JH, Kovacs A, Blumer KJ, Dorn GW II, and Muslin AJ. RGS4 restores cardiac contractility and normalizes hypertrophic gene induction in Gaq overexpressing mice. J. Mol. Cell. Card. 2001; 33:209-218.

Bruinsma JJ, Jirakulaporn T, Muslin AJ, and Kornfeld K. Zinc ions and cation diffusion facilitator proteins regulate ras-mediated signaling. Developmental Cell 2002; 2:567-578.

Wu C and MuslinAJ. Role of 14-3-3 proteins in early Xenopus development. Mech. Dev. 2002; 119:45-54.

Heximer SP, Knutsen RH, Sun X, Kaltenbronn KM, Rhee M-H, Peng N, Oliviera-dos-Santos A, Penninger JM, Muslin AJ, Steinberg TH, Wyss JM, Mecham RP, and Blumer KJ. Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice. J. Clin. Invest. 2003; 111:445-452.

Zhang S, Zhang CE, Weinheimer C, Courtois M, Kovacs A, Cheng AM, Wang Y, and Muslin AJ. The role of the Grb2-p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis. J. Clin. Invest. 2003; 111: 833-841.

Jenkins CM, Han X, Yang J, Mancuso DJ, Sims H, Muslin AJ, and Gross RW. Purification of recombinant human cPLA 2g and identification of farnesylation, proteolytic processing, and carboxymethylation by MALDI-TOF-TOF analysis. Biochemistry 2003; 42:11798-11807.

Zhang S, Ren J, Khan MF, Cheng AM, Abendschein D, and Muslin AJ. Grb2 is required for the development of neointima in response to vascular injury. Arteriosclerosis, Thrombosis, and Vascular Biology 2003; 23:1788-93. Epub 2003 Jul 03.

Zhang S, Ren J, Treskov I, Zhang CE, Wang Y, and Muslin AJ. Role of 14-3-3-mediated p38 MAPK inhibition in cardiac myocyte survival. Circulation Research 2003; 93: 1026 - 1028. Epub 2003 Oct 17.

Jirakulaporn Y, and Muslin AJ. CDF proteins modulate Raf-1 activation. J. Biol. Chem. 2004; 279:27807-27815. Epub April 19, 2004 .

Gurusamy N, Watanabe K, Ma M, Zhang S, Muslin AJ, Kodama M, and Aizawa Y.Dominant negative 14-3-3 promotes cardiomyocyte apoptosis in early stage of type I diabetes mellitus through activation of JNK. Biochem. Biophys. Res. Commun. 2004; 320:773-780.

Harris IS, Zhang S, Treskov I, Kovacs A, Weinheimer C, and Muslin AJ. Raf-1 kinase is required for cardiac hypertrophy and cardiac myocyte survival in response to pressure overload. Circulation 2004; 110:718-723. Epub 2004 Aug 02.

Harris IS, Treskov I, Rowley MW, Heximer S, Kaltenbronn K, Finck BN, Gross RW, Blumer KJ, Kelly DP, Muslin AJ. G protein signaling is required for the development of diabetic cardiomyopathy. Diabetes 2004; 53:3082-3090.

Ren J, Zhang S, Kovacs A, Wang Y, and Muslin AJ. Role of p38a MAPK in cardiac apoptosis and remodeling after myocardial infarction. J. Mol. Cell. Card. 2005;38:617-623.

Hindupur S and Muslin AJ. Septic shock induced from an implantable cardioverter-defibrillator lead-associated Candida albicans vegetation. J. Intervent. Card. Electrophysiol. 2005; 14: 55 -59.

Lau JMC, Wu C, and Muslin AJ. Differential role of 14-3-3 family members in Xenopus development. Developmental Dynamics 2006; 235:1761-1776.

DeBosch B, Lupu TS, Weinheimer C, Kovacs A, and Muslin AJ. Akt1 is required for physiologic cardiac growth. Circulation 2006; 113:2097-2104.

DeBosch B, Sambandam N, Weinheimer C, Courtois M, and Muslin AJ. Akt2 regulates cardiac metabolism and cardiomyocyte survival. J. Biol. Chem. 2006; 281: 32841-32851.

Schneider JG, Finck BN, Ren J, Standley KN, Takagi M, Maclean KH, Bernal-Mizrachi C, Muslin AJ, Kastan MB, Semenkovich CF. ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. Cell Metabolism 2006; 4: 377-389.

Lau JMC, Jin X, Ren J, Avery J, DeBosch BJ, Treskov I, Lupu TS, Kovacs A, Weinheimer C, Muslin AJ. The 14-3-3t Phosphoserine-Binding Protein is Required for Cardiomyocyte Survival. Mol. Cell. Biol. 2007; 27:1455-1466. Epub 2006 Dec 4.

Ren J, Zhang S, Zhao H, Courtois M, Ross FP, and Muslin AJ. b 3 integrin deficiency promotes cardiac hypertrophy and inflammation. J. Mol. Cell. Card. 2007; 42:367-377. Epub 2006 Dec 20.

Proctor BM. Ren J, Chen Z, Lupu TS, Schneider JG, Coleman T, Semenkovich CF, Muslin AJ. Grb2 is required for atherosclerotic lesion formation. Arteriosclerosis, Thrombosis, and Vascular Biology 2007; 27: 1361-1367. Epub 2007 March 15.

Treskov I, Jin X, Lupu TS, Courois M, Weinheimer C, Blumer KJ, Muslin AJ. Regulation of cardiac function by RGS3 and RGS4. ( Submitted.)

Proctor BM, Jin X, Lupu TS, Muglia LJ, Semenkovich CF, Muslin AJ. Requirement for p38 mitogen-activated protein kinase activity in neointima formation after vascular injury. ( Submitted.)

Siedlecki A, Jin X, Brennan DC, Muslin AJ. Renal injury induces pressure-independent cardiac hypertrophy that is reversible by mTOR inhibition. (Submitted.)

Research Interests:
A major focus of my laboratory is the study of molecular mechanisms that contribute to cardiac hypertrophic growth. In particular, we are interested in intracellular signaling pathways that regulate cardiac growth, survival and function. We use genetically-modified murine model systems to investigate the role of specific signaling proteins in cardiac hypertrophy. In particular, we study the role of heterotrimeric G proteins, mitogen-activated proteins kinases (MAPKs) and Akt family members in cardiac physiology by use of transgenic and knockout mouse model systems. More recently, we began to study the potential of murine embryonic stem cells to repair damaged heart after experimental myocardial infarction. We are focused on the selective differentiation of embryonic stem cells prior to cardiac delivery by overexpression of specific transcription factors.

Another focus of my laboratory is the study of signal transduction mechanisms in the development of atherosclerotic vascular disease. We determined that the linker protein Grb2 is required for atherosclerotic lesion development by use of a murine model system. Grb2 plays an important, but undefined, role in the uptake of cholesterol-containing particles by macrophages. We are currently investigating the molecular mechanisms involved in Grb2-mediated oxidized LDL uptake by macrophages in vitro and in animals.


· About the Division · Clinical Programs · Research Activities · Educational Programs · Centers of Excellence · Faculty Faculty Login · Links · Contact Us · Donors	Anthony J. Muslin, M.D. Oliver M. Langenberg Distinguished Professor of the Science and Practice of Medicine; Professor of Cell Biology and Physiology; Director, Cardiology Research Fellowship Program; Co-Director, Physician Scientist Training Program (PSTP), Washington University School of Medicine, St. Louis, MO Contact Information: Room 9910, Clinical Sciences Research Building (CSRB) Phone 314-747-3525 Fax 314-747-3545 E-mail: amuslin@wustl.edu Education and Training: Yale University, New Haven, Connecticut, B.A. History, 1980 Harvard Medical School, Boston, Massachusetts, M.D., 1984 1984-1987: Intern and Resident in Internal Medicine, Brigham & Women's Hospital, Boston, Massachusetts 1987-1989: Cardiology Fellow, University of California, San Francisco 1989-1992: Cardiology Research Fellow, University of California, San Francisco 1992-1994: Adjunct Assistant Professor of Medicine, University of California, San Francisco 1994-1999: Assistant Professor of Medicine, Washington University School of Medicine, St. Louis , Missouri 1999-2002: Associate Professor of Medicine, Washington University School of Medicine 2001-present: Director, Cardiology Research Fellowship Program 2001-present: Co-Director, Physician Scientist Training Program (PSTP) 2002-2006: Professor of Medicine, Washington University School of Medicine 2002-present: Professor of Cell Biology and Physiology, Washington University School of Medicine 2006-present: Oliver M. Langenberg Distinguished Professor of the Science and Practice of Medicine Honors and Awards: 1979: Phi Beta Kappa, Yale University 1980: Graduated magna cum laude, Yale University 1990: Henry Christian Memorial Award, American Federation for Clinical Research 1992: Physician Scientist Award, NHLBI 1999: Dr. Lee B. and Virginia G. Harrison Physician Scholar, Washington University School of Medicine 2000: Established Investigator Award, American Heart Association 2000: Elected Member, American Society for Clinical Investigation (ASCI) 2001: Clinical Scientist Award in Translational Research, Burroughs Wellcome Fund 2004: Elected Member, Association of American Physicians (AAP) 2006: Elected to Fellowship in the American Heart Association (FAHA), Council on Basic Cardiovascular Sciences 2007: Elected Member, Association of University Cardiologists (AUC) Clinical Expertise: Cardiovascular Care Unit (CCU) Selected Publications: Fantl WJ, Muslin AJ,Kikuchi A, Martin JA, MacNicol AM, Gross RW, and Williams LT. Activation of Raf-1 by 14-3-3 proteins. Nature 1994; 371, 612-615 (co-first authors). Hu Q, Klippel A, Muslin AJ, Fantl WJ, and Williams, LT. Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase. Science 1995; 268:100-102. MacNicol AM, Muslin AJ, Howard EL, Kikuchi A, MacNicol MC, and Williams LT. Regulation of Raf-1-dependent signaling during early Xenopus development. Mol. Cell. Biol. 1995; 15:6686-6693. Muslin AJ, Tanner JW, Allen PM, and Shaw AS. Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell 1996; 84:889-898. Kawabe T, Muslin AJ, and Korsmeyer SJ. Hox11 interacts with protein phosphatase 2A and disrupts a G2/M checkpoint. Nature 1997; 385, 454-458. Xing H, Kornfeld K, and Muslin AJ. KSR interacts with 14-3-3 protein and Raf. Current Biology1997; 7:294-300. Zhang S, Watson N, Zahner J, Blumer KJ, and Muslin AJ. RGS3 and RGS4 are G protein inhibitors in the heart. J. Mol. Cell. Card. 1998; 30:269-276. Tamirisa P, Blumer KJ, and Muslin AJ. RGS4 inhibits G protein signaling in cardiomyocytes. Circulation 1999; 99: 441-447. Jacobs D, Glossip D, Xing H, Muslin AJ, and Kornfeld K. Multiple docking sites on substrate recognition proteins form a modular system that mediates recognition by ERK MAP kinase. Genes Dev. 1999; 13:163-175. Bell B, Xing H, Yan K, Gautam N, and Muslin AJ. KSR-1 binds to G-protein bg subunits and inhibits bg-induced MAP kinase activation. J. Biol. Chem. 1999; 274:7982-7986. Goyal RK, Lin P, Kanungo J, Payne AS , Muslin AJ, and Longmore GD. Ajuba, a novel LIM protein, interacts with Grb2, augments MAP kinase activity in fibroblasts, and promotes meiotic maturation of Xenopus oocytes in a Grb2- and Ras-dependent manner. Mol. Cell. Biol. 1999; 19:4379-4389. Zhang S, Xing H, and Muslin AJ. Nuclear localization of PKU-a is regulated by 14-3-3 . J. Biol. Chem.1999; 275:24865-24872. Rogers J, Tamirisa P, Kovacs A, Weinheimer C, Blumer KJ, Kelly DJ, and Muslin AJ. RGS4 causes increased mortality and reduced cardiac hypertrophy in response to pressure overload. J. Clin. Invest. 1999; 104:567-576. MacNicol M, Muslin AJ, and MacNicol AM. Disruption of the 14-3-3 Binding Site within the B-Raf Kinase Domain Uncouples Catalytic Activity from PC12 Cell Differentiation. J. Biol. Chem. 2000; 275:3803-3809. Xing H, Zhang S, Weinheimer C, Kovacs A, and Muslin AJ. 14-3-3 proteins inhibit apoptosis and differentially regulate MAPK cascades. EMBO J. 2000; 19:349-358. Wu C, Zeng Q, Blumer KJ, and Muslin AJ. RGS proteins inhibit Xwnt-8 in Xenopus embryonic development. Development 2000; 127:2773-2784. Rogers JH, Kovacs A, Blumer KJ, Dorn GW II, and Muslin AJ. RGS4 restores cardiac contractility and normalizes hypertrophic gene induction in Gaq overexpressing mice. J. Mol. Cell. Card. 2001; 33:209-218. Bruinsma JJ, Jirakulaporn T, Muslin AJ, and Kornfeld K. Zinc ions and cation diffusion facilitator proteins regulate ras-mediated signaling. Developmental Cell 2002; 2:567-578. Wu C and MuslinAJ. Role of 14-3-3 proteins in early Xenopus development. Mech. Dev. 2002; 119:45-54. Heximer SP, Knutsen RH, Sun X, Kaltenbronn KM, Rhee M-H, Peng N, Oliviera-dos-Santos A, Penninger JM, Muslin AJ, Steinberg TH, Wyss JM, Mecham RP, and Blumer KJ. Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice. J. Clin. Invest. 2003; 111:445-452. Zhang S, Zhang CE, Weinheimer C, Courtois M, Kovacs A, Cheng AM, Wang Y, and Muslin AJ. The role of the Grb2-p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis. J. Clin. Invest. 2003; 111: 833-841. Jenkins CM, Han X, Yang J, Mancuso DJ, Sims H, Muslin AJ, and Gross RW. Purification of recombinant human cPLA 2g and identification of farnesylation, proteolytic processing, and carboxymethylation by MALDI-TOF-TOF analysis. Biochemistry 2003; 42:11798-11807. Zhang S, Ren J, Khan MF, Cheng AM, Abendschein D, and Muslin AJ. Grb2 is required for the development of neointima in response to vascular injury. Arteriosclerosis, Thrombosis, and Vascular Biology 2003; 23:1788-93. Epub 2003 Jul 03. Zhang S, Ren J, Treskov I, Zhang CE, Wang Y, and Muslin AJ. Role of 14-3-3-mediated p38 MAPK inhibition in cardiac myocyte survival. Circulation Research 2003; 93: 1026 - 1028. Epub 2003 Oct 17. Jirakulaporn Y, and Muslin AJ. CDF proteins modulate Raf-1 activation. J. Biol. Chem. 2004; 279:27807-27815. Epub April 19, 2004 . Gurusamy N, Watanabe K, Ma M, Zhang S, Muslin AJ, Kodama M, and Aizawa Y.Dominant negative 14-3-3 promotes cardiomyocyte apoptosis in early stage of type I diabetes mellitus through activation of JNK. Biochem. Biophys. Res. Commun. 2004; 320:773-780. Harris IS, Zhang S, Treskov I, Kovacs A, Weinheimer C, and Muslin AJ. Raf-1 kinase is required for cardiac hypertrophy and cardiac myocyte survival in response to pressure overload. Circulation 2004; 110:718-723. Epub 2004 Aug 02. Harris IS, Treskov I, Rowley MW, Heximer S, Kaltenbronn K, Finck BN, Gross RW, Blumer KJ, Kelly DP, Muslin AJ. G protein signaling is required for the development of diabetic cardiomyopathy. Diabetes 2004; 53:3082-3090. Ren J, Zhang S, Kovacs A, Wang Y, and Muslin AJ. Role of p38a MAPK in cardiac apoptosis and remodeling after myocardial infarction. J. Mol. Cell. Card. 2005;38:617-623. Hindupur S and Muslin AJ. Septic shock induced from an implantable cardioverter-defibrillator lead-associated Candida albicans vegetation. J. Intervent. Card. Electrophysiol. 2005; 14: 55 -59. Lau JMC, Wu C, and Muslin AJ. Differential role of 14-3-3 family members in Xenopus development. Developmental Dynamics 2006; 235:1761-1776. DeBosch B, Lupu TS, Weinheimer C, Kovacs A, and Muslin AJ. Akt1 is required for physiologic cardiac growth. Circulation 2006; 113:2097-2104. DeBosch B, Sambandam N, Weinheimer C, Courtois M, and Muslin AJ. Akt2 regulates cardiac metabolism and cardiomyocyte survival. J. Biol. Chem. 2006; 281: 32841-32851. Schneider JG, Finck BN, Ren J, Standley KN, Takagi M, Maclean KH, Bernal-Mizrachi C, Muslin AJ, Kastan MB, Semenkovich CF. ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. Cell Metabolism 2006; 4: 377-389. Lau JMC, Jin X, Ren J, Avery J, DeBosch BJ, Treskov I, Lupu TS, Kovacs A, Weinheimer C, Muslin AJ. The 14-3-3t Phosphoserine-Binding Protein is Required for Cardiomyocyte Survival. Mol. Cell. Biol. 2007; 27:1455-1466. Epub 2006 Dec 4. Ren J, Zhang S, Zhao H, Courtois M, Ross FP, and Muslin AJ. b 3 integrin deficiency promotes cardiac hypertrophy and inflammation. J. Mol. Cell. Card. 2007; 42:367-377. Epub 2006 Dec 20. Proctor BM. Ren J, Chen Z, Lupu TS, Schneider JG, Coleman T, Semenkovich CF, Muslin AJ. Grb2 is required for atherosclerotic lesion formation. Arteriosclerosis, Thrombosis, and Vascular Biology 2007; 27: 1361-1367. Epub 2007 March 15. Treskov I, Jin X, Lupu TS, Courois M, Weinheimer C, Blumer KJ, Muslin AJ. Regulation of cardiac function by RGS3 and RGS4. ( Submitted.) Proctor BM, Jin X, Lupu TS, Muglia LJ, Semenkovich CF, Muslin AJ. Requirement for p38 mitogen-activated protein kinase activity in neointima formation after vascular injury. ( Submitted.) Siedlecki A, Jin X, Brennan DC, Muslin AJ. Renal injury induces pressure-independent cardiac hypertrophy that is reversible by mTOR inhibition. (Submitted.) Research Interests:* A major focus of my laboratory is the study of molecular mechanisms that contribute to cardiac hypertrophic growth. In particular, we are interested in intracellular signaling pathways that regulate cardiac growth, survival and function. We use genetically-modified murine model systems to investigate the role of specific signaling proteins in cardiac hypertrophy. In particular, we study the role of heterotrimeric G proteins, mitogen-activated proteins kinases (MAPKs) and Akt family members in cardiac physiology by use of transgenic and knockout mouse model systems. More recently, we began to study the potential of murine embryonic stem cells to repair damaged heart after experimental myocardial infarction. We are focused on the selective differentiation of embryonic stem cells prior to cardiac delivery by overexpression of specific transcription factors. Another focus of my laboratory is the study of signal transduction mechanisms in the development of atherosclerotic vascular disease. We determined that the linker protein Grb2 is required for atherosclerotic lesion development by use of a murine model system. Grb2 plays an important, but undefined, role in the uptake of cholesterol-containing particles by macrophages. We are currently investigating the molecular mechanisms involved in Grb2-mediated oxidized LDL uptake by macrophages in vitro and in animals.