Charles E. Murry

Joint Professor of Pathology, Cardiology, and Bioengineering

murry@u.washington.edu
Phone: (206)616-8685
South Lake Union campus:
Office: 850 Republican St. Rm 453

charles_murry_candid

Lab Website
How I am inventing the future of medicine
Since 1996, the Murry lab has worked to understand the mechanisms that underlie cardiovascular disease and to develop new treatments. We have a longstanding interest in the biology of myocardial infarction (heart attacks), and in particular, how the heart heals after infarction. The lab has a major focus in stem cell biology and tissue engineering, where we seek to understand the molecular basis for cardiovascular differentiation, and to harness the potential of stem cells to repair the heart. Recently, our group has begun to use stem cell approaches to study genetically based cardiomyopathies. We are deriving induced pluripotent stem cells (iPSCs) from patients with cardiomyopathy, and using cell biology and tissue engineering for “disease in a dish” studies.
Research Interests
Myocardial infarction
Stem cells
Tissue repair and regeneration
Tissue engineering
Angiogenesis
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.

Education
MD, Duke University, 1989
PhD (pathology), Duke University, 1988
BS, University of North Dakota, 1982
Postdoc Information
Postdoctoral Fellowship (Vascular Molecular biology), University of Washington, 1991-1996
Awards and Honors
2003, Alumnus of the Year, Bismarck State College
2000, Presidential Early Career Award in Science and Engineering,
UW Bioengineering Courses Taught
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

 

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