Research Themes:
Biomaterials and Regenerative Medicine
Molecular and Cellular Engineering

Education

PhD (pathology) Duke University, 1988
MD, Duke University, 1989
BS, University of North Dakota, 1982

Research Interests

• Myocardial infarction
• stem cells
• tissue repair and regeneration
• tissue engineering
• angiogenesis

Contact Information

Center for Cardiovascular Biology
University of Washington
Box 358050
815 Mercer St, Room 453
Phone: 206-616-8685
Fax: 206-897-1540
E-mail
Lab Web site: http://www.pathology.washington.edu/research/labs/murry/

Research Description

Overview
Myocardial infarctions (heart attacks) are the number one cause of death in the industrialized world. Infarcts occur when a coronary artery becomes obstructed, resulting in the rapid death of myocardium from ischemia (deficiency of blood flow). The heart has no significant intrinsic regenerative ability. As a result, infarcts heal by scar formation, and many patients suffer from heart failure after an infarct. Our group is interested in the biology of myocardial infarction, both in defining the molecular mechanisms that underlie the heart's normal wound healing processes and in developing molecular and cell-based approaches to improve infarct repair. We are a multidisciplinary group, doing basic work in molecular biology and regulation of gene expression, cell biology, tissue engineering, mouse models of disease, and analyses of human tissues. The following serves to highlight some of the work underway in the lab.
Stem Cell Studies
Our lab is working with both adult and pluripotent (embryonic and iPSC) stem cells, with an aim to develop cellular approaches to regenerate the heart. Our work in adult stem cells is focused on creating transgenic/knock-in mice to track progenitor cells in the heart. We will use genetic pulse-chase techniques to mark candidate progenitor populations and then follow their appearance into other compartments of the heart such as muscle cells or blood vessels. We are working with mesenchymal stem cells to enhance survival of transplanted cardiomyocytes via paracrine signaling pathways. Pluripotent stem cell studies are focused on molecular pathways involved in cardiovascular differentiation, including the use of high throughput sequencing to understand chromatin remodeling and transcription factor binding. We recently identified key roles for signaling through Wnt and VEGF pathways in determining cardiac, smooth muscle and endothelial fate. We are also using these early cells to repair the infarcted heart via cell transplantation and have shown that stem cell-derived human myocardium prevents development of heart failure after experimental infarction. Finally, we have created an 8-site pediatric cardiology network for generating induced pluripotent stem cells (iPSCs) from children with genetic heart muscle disease. We will use these iPSCs to create cardiac muscle carrying the disease-causing genes and study the molecular and physiological basis for contractile and rhythm disorders.

Tissue Engineering
Tissue engineering is a new discipline that combines the worlds of cell biology, materials science and quantitative approaches to mathematical modeling and analyses typical of engineering. Our goal is to create a ''patch'' of contractile tissue ex vivo and implant this onto an infarcted heart for cardiac repair. Current approaches involve seeding cells onto synthetic, biodegradable scaffolds and utilizing a ''cells in gels'' approach, where cells are seeded into hydrophilic gels containing microencapsulated growth factors and cytokines for timed release.

Honors & Awards

• 2003, Alumnus of the Year, Bismarck State College
• 2000, Presidential Early Career Award in Science and Engineering,

Selected Publications

• Murry CE, Lee RT (2009) Turnover after the fallout, Science, 324 (5923), 47-48
• Tulloch NL, Pabon L, Murry CE (2008) Get with the (re)program: Cardiovascular potential of skin-derived induced pluripotent stem cells, Circulation, 118 (5), 472-475
• Sampath P, Pritchard DK, Pabon L, Reinecke H, Schwartz SM, Morris DR, Murry CE (2008) A hierarchical network controls protein translation during murine embryonic stem cell self-renewal and differentiation, Cell Stem Cell, 2 (5), 448-460
• Golob JL, Paige SL, Muskheli V, Pabon L, Murry CE (2008) Chromatin remodeling during mouse and human embryonic stem cell differentiation, Dev Dyn, 237 (5), 1389-1398
• Robey TE, Saiget MK, Reinecke H, Murry CE (2008) Systems approaches to preventing transplanted cell death in cardiac repair, J Mol Cell Cardiol
• Sussman MA, Murry CE (2008) Bones of contention: Marrow-derived cells in myocardial regeneration, J Mol Cell Cardiol
• Anderl JN, Robey TE, Stayton PS, Murry CE (2008) Retention and loss of microspheres injected into ischemic myocardium: Implications for cell grafting and localized drug delivery, J Biomed Materials Res Part A
• Murry CE, Keller G (2008) Differentiation of embryonic stem cells into clinically relevant populations: Lessons from embryonic development, Cell, 132, 661-680
• Robey TE, Murry CE (2008) Absence of regeneration in the MRL mouse heart following infarction or cryoinjury, Cardiovasc Pathol, 17 (1), 6-13
• Virag JAI, Hardouin S, Rolle M, Reece J, Feigl EO, Murry CE (2007) Basic FGF regulates myocardial infarct repair: Effects on cell proliferation, scar contraction, and ventricular function, Am J Pathol, 171 (5), 1431-1440
• Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK, Xu C, Hassanipour M, Police S, O'Sullivan C, Collins L, Minami E, Gill EA, Ueno S, Yuan C, Gold J, Murry CE (2007) Transplantation of human cardiomyocytes derived from embryonic stem cells in pro-survival factors enhances function of of infarcted hearts, Nature Biotechnology, 25 (9), 1015-1024
• Nourse MB, Rolle MW, Pabon LM, Murry CE (2007) Selective control of endothelial cell proliferation with a synthetic dimerizer for FGF receptor-1, Lab Invest, 87 (8), 828-835
• Stevens K, Rolle M, Minami E, Ueno S, Nourse M, Virag JA, Reinecke H, Murry CE (2007) Chemical dimerization of fibroblast growth factor receptor-1 induces myoblast proliferation, increases intracardiac graft size, and reduces ventricular dilation in infarcted hearts, Human Gene Therapy, 18 (5), 401-412
• Nussbaum J, Minami E, Laflamme MA, Virag JA, Ware CB, Masino A, Muskheli V, Pabon L, Reinecke H, Murry CE (2007) Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response, FASEB J, 21 (7), 1345-1357
• Ueno S, Weidinger G, Osugi T, Kohn A, Golob J, Pabon L, Reinecke H, Moon RT, Murry CE (2007) Biphasic role for Wnt/ β-catenin signaling in cardiac specification in zebrafish and embryonic stem cells, Proc Natl Acad Sci, 104 (23), 9685-9690
• Laflamme MA, Zbinden S, Epstein SE, Murry CE (2007) Cell-based cardiac repair: Pathophysiological mechanisms, Ann Rev Pathol Mech Disease, 2, 307-339
• Gregorevic P, Allen JM, Minami E, Blankinship MJ, Haraguchi M, Meuse L, Finn E, Adams ME, Froehner SC, Murry CE, Chamberlain JS (2006) rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice, Nat Med, 12 (7), 787-789