Molecular Pathology Labratory
Dr. Li’s research team aims to focus on two major areas of investigation: the properties of dedifferentiation and adult stem cells, and fibrous scar formation in the injured and diseased neuromuscular system.
De-differentiation and adult stem cells:
The objective of this project is to examine adult stem cells, such as those of skin and muscle, as a tool to repair injured and congenitally diseased tissues (muscle, tendon, spinal cord, and others) and determine the potency and viability of various potential dedifferentiation stimulating compounds in vitro and in vivo. In Dr. Li’s previous work, he has already observed some growth factors that were able to stimulate dedifferentiation in injured skeletal muscle. Using gene therapy and cell transplantation techniques, Dr. Li will investigate whether it is possible to take advantage of the dedifferentiation process inducible in mammalian skeletal muscle tissue to reconstruct the limb of another vertebrate (newt and salamander) model. The overall goal of this project is to increase the number of stem cell-like cells made available from the skin and skeletal muscle pool. The human body contains a large amount of easily accessible skin and skeletal muscle that is the likely source of numerous populations of adult stem cells that have an inherent capacity to differentiate into different phenotypic lineages and regenerate various tissues, including skeletal muscle, the spinal cord, various nerve cells, and liver. To be able to more fully comprehend and control this process and the intricacies of signaling involved would be of exceptionally important clinical value.
Fibrosis in Skeletal Muscular System:
Amphibians, such as newts and salamanders can rebuild a limb after injury. However, injured mammalian tissue, including that of humans, is usually replaced with fibrotic scar tissue at the end of the healing process. This project’s objective is to determine the mechanism(s) behind dedifferentiation in amphibians, and ascertain the relationship(s) between dedifferentiation and fibrotic scar tissue formation. To date, Dr. Li has already 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 reduce muscle fibrosis and improve muscle healing. However, injuries cannot always be treated before fibrosis occurs, especially in the case of 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 that subsequently inhibits muscle regeneration, and weakens the injured muscle, making it more susceptible to re-injury. Muscle scarring also poses a significant problem to Duchenne muscular dystrophy (DMD) patients, whose muscles can be replete with scar tissue, making them very weak by their teenage years. Dr. Li’s project aims to examine the role of MMPs (matrix-metalloproteinases), to digest scar tissue after fibrosis has already occurred, thus enhancing muscle cell migration, fusion, regeneration, and improving the overall process of muscle healing.