The goal of this research is to increase understanding of the mechanisms underlying muscle injury, treatment, and recovery. My hypothesis is that cytokeretins K8 & K19 play an integral part in the organization and function of the sarcolemma of skeletal muscle. I will use functional, morphological, and molecular biological approaches to test this hypothesis through 3 specific aims: 1) a: To adapt a model of muscle injury to mice and compare subsequent contractile function to mice with a known dystrophinopathy (mdx mice), b: to compare forces of mdx and wild-type (wt) single-fibers to the whole-muscle findings and to mdx fibers transfected with a virus expressing a functional dystrophin, 2) To determine whether muscles lacking cytokeratin K8 or K19 are dystrophic and/or more susceptible to injury, and if replacement of the missing subunit into muscle fibers by adenoviral transfection corrects the dystrophy or alters susceptibility to injury, 3) To learn if overexpression of K8 or K19 results in myopathy. There are marked similarities in the histopathology of some muscular dystrophies and the changes in muscle induced by injury. The proposed research is designed to elucidate some of the shared cellular and molecular mechanisms.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HD047099-01
Application #
6791638
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Nitkin, Ralph M
Project Start
2004-04-30
Project End
2006-04-29
Budget Start
2004-04-30
Budget End
2005-04-29
Support Year
1
Fiscal Year
2004
Total Cost
$42,976
Indirect Cost
Name
University of Maryland Baltimore
Department
Physiology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Stone, Michele R; O'Neill, Andrea; Lovering, Richard M et al. (2007) Absence of keratin 19 in mice causes skeletal myopathy with mitochondrial and sarcolemmal reorganization. J Cell Sci 120:3999-4008
Lovering, Richard M; Roche, Joseph A; Bloch, Robert J et al. (2007) Recovery of function in skeletal muscle following 2 different contraction-induced injuries. Arch Phys Med Rehabil 88:617-25
Russ, David W; Lovering, R M (2006) Influence of activation frequency on cellular signalling pathways during fatiguing contractions in rat skeletal muscle. Exp Physiol 91:957-66