Fibrosis and related research:

Description of projects available to graduate students:
Salamanders can rebuild a limb after injury. However, injured mammalian tissue (including human) is usually replaced with fibrotic scar tissue at the end of healing. What is the mechanism behind dedifferentiation? What is the relationship between dedifferentiation and fibrotic scar tissue formation? Dr. Li’s future study will answer these questions. In fact, Dr. Li has made some key findings pertaining to fibrosis (i.e., scar tissue formation) and its role in inhibiting muscle healing. Because scar tissue often replaces damaged myofibers, fibrosis is likely a contributing factor in the tendency for muscle injury recurrence. Dr. Li and his team have demonstrated, for the first time, the central role of TGF-β1 in skeletal muscle fibrosis. Based upon Dr. Li's histological and physiological findings in this area, his subsequent research has shown that the use of anti-fibrotic agents, such as decorin, suramin, relaxin, and γ-INF (which negate the effects of TGF-β1), can prevent muscle fibrosis and improve muscle healing. However, injuries cannot always be treated before fibrosis occurs, especially as is the case in some chronic diseases in which scar tissue is formed prior to therapy. In muscles suffering from trauma, scar tissue forms in a time-dependent manner, inhibits muscle regeneration, and weakens the injured muscle, thereby making it more susceptible to re-injury. Muscle scarring also poses a significant problem to Duchenne Muscular Dystrophy (DMD) patients, whose muscles can be rife with scar tissue, and therefore very weak, by their teenage years. One of Dr. Li’s project aims is to identify MMPs (matrix-metalloproteinases, collagen digesting enzymes), which digest scar tissue after fibrosis has already occurred, and enhances muscle cell migration, fusion and regeneration. Moreover, this project also proposes to investigate if MMP1 gene therapy could increase myogenic cell transplantation in dystrophic skeletal muscles through local muscle injection and blood stream injection. With this novel idea, we expect that this approach would increase the clinical applicability of myogenic cell transplantation therapy for various musculoskeletal congenital diseases. We expect the proposed application of MMP1 to significantly improve the clinical practicality of myogenic cell transplantation and to greater functional muscle recovery.

Techniques graduate student will learn:
Histological background as well as immune staining