DESCRIPTION (provided by applicant): My long term career goal is to become an independent academic researcher, making substantial contributions in the field of muscle physiology that are translated into clinically relevant therapies for those with muscle diseases. This award mechanism would be instrumental in the providing the ability to reach goal by providing the continued training necessary for me to transition to independence. My background in bioengineering and muscle physiology research has provided a focus on outstanding question of how muscle fibrosis leads to impaired function and regeneration. To adequately address this question I have garnered the support of an outstanding mentor in bioengineering of cellular responses to extracellular matrix properties, Dr. Discher. His mentorship will be supplemented by that of my co-mentor Dr. Barton, who will continue to provide exceptional mentorship in muscle physiology. Further guidance will be provided by Dr. Soslowsky, who will serve on my advisory committee. This committee will meet regularly to ensure adequate progress toward project milestones, assess alternative strategies when necessary, and monitor my transition to becoming independent. I will also work with collaborators; Dr. Iwamoto who has expertise in severe muscle injury models and Dr. Yamauchi who is an authority on collagen post-transcriptional modifications. The environment at Penn is ideal for conducting the proposed research, in large part from the Pennsylvania Muscle Institute which provides various training opportunities among a cadre of engaged faculty interested in a variety of aspects of muscle. Didactics during the mentored phase of the award will broaden the scope of my research and lower barriers to attempting new approaches in my career. Penn also provides support services for postdocs acquiring faculty positions that I will take full advantage of through the Biomedical Postdoctoral Program Office. The outstanding institutional environment at the University of Pennsylvania will be supplemented by training at the University of Florida with co-mentor Dr. Barton and at the University of North Carolina with collaborator Dr. Yamauchi. The results of this research proposed will be shared with the public through peer reviewed publications and presentations at national conferences with relevant interests. While I will take leadership of this project, the support system engaged will ensure every opportunity for success in acquiring my goals. Fibrosis is the pathologic accumulation of extracellular matrix (ECM) components within a tissue leading to disrupted architecture and loss of function. Skeletal muscle undergoes fibrosis in response to many conditions including muscular dystrophies and severe muscle injury. Within skeletal muscle the ECM not only provides a cell scaffold, but has the additional role of transmitting forces produced by muscle fibers, making ECM critical to muscle function. My past research in skeletal ...