Penn Cardiovascular Institute

Penn Cardiovascular Institute Research Directory

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H. Lee Sweeney, Ph.D

William Maul Measey Professor in Physiology
Department: Physiology

Contact information
Richards Bldg., Rm. B400
3700 Hamilton Walk
Philadelphia, PA 19104-6085
Office: (215) 898-8727
Fax: (215) 573-2273
S.B. (Biochemistry)
Massachusetts Institute of Technology, 1975.
A.M. (Physiology)
Harvard University, 1980.
Ph.D. (Physiology and Biophysics)
Harvard University, 1984.
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Description of CVI Expertise

CVI Program Unit Administrator:
Myocyte Biology / Heart Failure

CVI Research Description:
Function of contractile proteins.
Mechanisms of DCM and HCM.

Dr. Sweeney's research program addresses the molecular basis of cellular movement and force generation. His approach encompasses investigations on single molecules, single cells and whole organisms. At the level of the single molecule, the work examines the basic design and function of the molecular motor, myosin. These studies combine protein engineering with biochemical and structural analyses. At the level of isolated cells (cultured myocytes), the research program has two aspects: 1) investigation of the role of various proteins either in the generation of force, or in the transmission of force across the cell membrane, and 2) the process of assembly of the contractile apparatus. Studies at the whole animal level involve gene transfer into muscle (both germline and somatic cell). Somatic cell gene transfer (utilizing viruses) allows the assessment of acute alterations in cell structure and function following viral-driven expression of a single protein. In response to acute changes in properties, feedback pathways intrinsic and extrinsic to the muscle cell signal alterations in the muscle gene expression program that result in an adaptive response. This new approach allows critical evaluation of principles of muscle cell design as well as evaluation of possible causes of and treatments for muscle diseases. Currently, Dr. Sweeney is studying two diseases, Duchenne muscular dystrophy and hypertrophic cardiomyopathy, with this approach.

Selected Publications

Sen Shamik, Tewari Manorama, Zajac Allison, Barton Elisabeth, Sweeney H Lee, Discher Dennis E: Upregulation of paxillin and focal adhesion signaling follows Dystroglycan Complex deletions and promotes a hypertensive state of differentiation. European journal of cell biology Jul 2010.

Barton Elisabeth R, Wang Bing Jing, Brisson Becky K, Sweeney H Lee: Diaphragm displays early and progressive functional deficits in dysferlin-deficient mice. Muscle & nerve 42(1): 22-9, Jul 2010.

Mathur Sunita, Lott Donovan J, Senesac Claudia, Germain Sean A, Vohra Ravneet S, Sweeney H Lee, Walter Glenn A, Vandenborne Krista: Age-related differences in lower-limb muscle cross-sectional area and torque production in boys with Duchenne muscular dystrophy. Archives of physical medicine and rehabilitation 91(7): 1051-8, Jul 2010.

Wang Bingjing, Yang Zhaohui, Brisson Becky K, Feng Huisheng, Zhang Zhiqian, Welch Ellen, Peltz Stuart, Barton Elisabeth R, Brown Robert H, Sweeney H Lee: Membrane blebbing as an assessment of functional rescue of dysferlin-deficient human myotubes via nonsense suppression. Journal of applied physiology (Bethesda, Md. : 1985) Jun 2010.

George Isaac, Bish Lawrence T, Kamalakkannan Gayathri, Petrilli Christopher M, Oz Mehmet C, Naka Yoshifumi, Sweeney H Lee, Maybaum Simon: Myostatin activation in patients with advanced heart failure and after mechanical unloading. European journal of heart failure : journal of the Working Group on Heart Failure of the European Society of Cardiology 12(5): 444-53, May 2010.

Morine K, Sleeper MM, Barton ER, Sweeney HL: Overexpression of SERCA1a in the mdx diaphragm reduces susceptibility to contraction induced damage. Hum Gene Ther 2010 Notes: Epub ahead of print.

Morine Kevin J, Bish Lawrence T, Pendrak Klara, Sleeper Meg M, Barton Elisabeth R, Sweeney H Lee: Systemic myostatin inhibition via liver-targeted gene transfer in normal and dystrophic mice. PloS one 5(2): e9176, 2010.

Bish LT, Morine KJ, Sleeper MM, Sweeney HL : Myostatin is upregulated following stress in an Erk-dependent manner and negatively regulates cardiomyocyte growth in culture and in a mouse model. PLoS ONE 5(4): e10230, 2010.

Phichith Denis, Travaglia Mirko, Yang Zhaohui, Liu Xiaoyan, Zong Alan B, Safer Daniel, Sweeney H Lee: Cargo binding induces dimerization of myosin VI. Proceedings of the National Academy of Sciences of the United States of America 106(41): 17320-4, Oct 2009.

Mukherjea Monalisa, Llinas Paola, Kim HyeongJun, Travaglia Mirko, Safer Daniel, Ménétrey Julie, Franzini-Armstrong Clara, Selvin Paul R, Houdusse Anne, Sweeney H Lee: Myosin VI dimerization triggers an unfolding of a three-helix bundle in order to extend its reach. Molecular cell 35(3): 305-15, Aug 2009.

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Last updated: 08/26/2010
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