Grants Funded

Abstract
Tendon injuries occur frequently in physically active individuals and as a result of trauma, but the clinical outcomes for these injuries can be poor. Even with surgical repair, excessive scar tissue formation can severely limit function. Unlike our understanding of skeletal muscle regeneration, very little is known about the cellular and molecular mechanisms of how tendons heal. Therefore, a greater insight into this process may lead to targeted therapies that could potentially serve as an adjunct to surgery. Tendon healing is orchestrated by fibroblasts, which have a well-described role in synthesizing and remodeling extracellular matrix (ECM) after tissue injury. In many organ systems, epithelial cells contribute to the pool of fibroblasts, which can then regenerate damaged ECM. This sequence of biologic events is known as epithelial-to-mesenchymal transition (EMT). While most tendons are surrounded by sheets of epithelial cells, and these tissue layers could provide a source of fibroblasts to repair injured tendon ECM, the role of EMT in tendon repair has not been previously described. In this proposal, the main objective is to determine if EMT is contributing to the repair of injured tendon and its overall importance in tendon regeneration. Our preliminary data suggest that EMT-related signaling molecules are highly expressed in both the epithelium surrounding tendon as well as at the repair site following an acute tear and repair. Using mice wherein these EMT-related signaling molecules can be deleted only in cells giving rise to tendon fibroblasts, the impact of these factors on tendon regeneration can be investigated by measuring changes in gene expression, histology and tendon mechanics. Additionally, in a series of lineage tracing experiments using transgenic mice, the epithelium surrounding tendon can be labelled with a fluorescent protein to determine if the fibroblasts emerging from it are in fact true descendents of epithelial cells. The proposed studies will greatly expand our knowledge of basic tendon fibroblast biology and there is potential for a real clinical impact on the practice of plastic surgery. Findings from this proposal could lead to future translational studies involving the design of new therapeutics directed at improving tendon healing after surgical repair, and may provide useful cellular markers that can be applied to tissue engineering approaches for the reconstruction of critical tendon defects.

Biography
A native of Southeastern Michigan, Dr. Sugg completed his undergraduate studies in Chemistry as a Presidential Scholar at Wayne State University. He then earned a medical degree from the Wayne State University School of Medicine. With enthusiasm for complex problem solving, Dr. Sugg entered the Integrated Plastic and Reconstructive Surgery Residency Program at the University of Michigan in July 2007. He spent one year in the Neuromuscular Lab as a postdoctoral fellow investigating ways to provide sensation to prosthetic limbs. More recently, he enrolled into the Program in Biomedical Sciences at the University of Michigan to pursue a PhD degree in Molecular and Integrative Physiology. The focus of his dissertation is on the cellular and molecular mechanisms that regulate tendon growth and regeneration.