Cellular and Molecular Pathology (CMP)
Graduate Training Program
 

Faculty and Their Research Interests

   Faculty Index

  BulletDr. Becich
  BulletDr. D. Becker
  BulletDr. J. Becker
  BulletDr. Billiar
  BulletDr. Blair
  BulletDr. Bostwick
  BulletDr. Bowser
  BulletDr. Chaillet
  BulletDr. Chang
  BulletDr. Cheng
  BulletDr. Chu
  BulletDr. Clemens
  BulletDr. DeFrances
  BulletDr. Delude
  BulletDr. Demetris
  BulletDr. Dong
  BulletDr. Donnenberg
  BulletDr. Gandhi
  BulletDr. Giannoukakis
  BulletDr. Gnarra
  BulletDr. Grandis
  BulletDr. Hebda
  BulletDr. Huard
  BulletDr. Kaminski
  BulletDr. Katyal
  BulletDr. Kelavkar
  BulletDr. Klunk
  BulletDr. Kulich
  BulletDr. Lagasse
  BulletDr. Latimer
  BulletDr. Luyuan Li
  BulletDr. Yong Li
  BulletDr. Youhua Liu
  BulletDr. Lokshin
  BulletDr. Luo
  BulletDr. Lyons-Weiler
  BulletDr. Monga
  BulletDr. Mars
  BulletDr. Michalopoulos
  BulletDr. Ochoa
  BulletDr. O'Keefe
  BulletDr. Oltvai
  BulletDr. Oury
  BulletDr. Pflug
  BulletDr. Piganelli
  BulletDr. Saunders
  BulletDr. Shapiro
  BulletDr. Stolz
  BulletDr. Strom
  BulletDr. Surti
  BulletDr. Vodovotz
  BulletDr. Wang
  BulletDr. Wells
  BulletDr. Wenzel
  BulletDr. Wiley
  BulletDr. Wu
  BulletDr. Yin
  BulletDr. Zarnegar


V-line Dr. Yong Li

Yong Li, Assistant Professor
MD, Shanghai Second Medical University, China 1993
PhD, Chongqing Third Medical University, China 1996
Email: yongli@pitt.edu




Research Interest:

1. Dedifferentiation 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.

2. 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-¦Â1 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 ¦Ã-INF (which negate the effects of TGF-¦Â1), 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.

Recent Publication

  1. Li Y, Huard J. Muscle derived stem cell transdifferentiate into myofibroblast in injured muscle. American J Pathology. 2002; 161 (3): 895-907.
  2. Huard J, Yokoyama T, Pruchnic R, Qu Z, Li Y, Lee JY, Somogyi G, de Groat WC, Chancellor MB. The use of muscle derived stem cells for urological dysfunction. Gene Therapy 2002; 9(23): 1617-1626.
  3. Chan YS, Li Y, Horaguchi T, Foster W, Somogi G, Fu FH, Huard J. The antifibrotic effects of suramin in injured skeletal muscle after laceration. J Apply Physiology 2003; 95:771-780.
  4. Foster W, Li Y, Arvydas Usas, George Somogyi, Huard J. gamma-INF as an antifibrotic agent in skeletal muscle. J Orthopeadic Research 2003;21:798-804.
  5. Sato K, Li Y, Foster W, Fukushima K, Badlani N, Nodachi N, Usas A, Fu FH, Huard J. Improvement of muscle healing through enhancement of muscle regeneration and prevention of fibrosis. Muscle & Nerve 2003; 28(3):365-372.
  6. Li Y, Foster W, Deasy BM, Chan YS, Prisk V, Tang Y, Cummins J, Huard J. TGF-beta1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: a key event in muscle fibrogenesis. American J Pathology 2004;164(3):1007-1019.
  7. Chan YS, Li Y, Horaguchi T, Foster W, Somogi G, Fu FH, Huard J. The use of suramin, an antifibrotic agent, to improve muscle recovery after strain injury. Am J Sport Medicine 2005; 33(1): 43-51.
  8. Li Y, Negishi S, Sakamoto M, Arvydas Usas, Huard, J. The use of relaxin improves healing in injured muscle. Annals of N. Y. Academic Science. 2005; 1041:395-398.
  9. Chen X, Mao Z, Liu S, Liu H, Wang X, Wu H, Wu Y, Zhao T, Fan W, Li Y, Yew DT, Kindler PM, Li L, He Q, Qian L, Wang X, Fan M. Dedifferentiation of Adult Human Myoblasts Induced by CNTF In Vitro. Molecular Biology of Cell. 2005;16(7):3140-51. Epub 2005 Apr 20.
  10. Negishi S, Li Y, Usas A, Ryosuke K, Foster W, Fu FH, Huard J. The effect of relaxin treatment in skeletal muscle injuries. Am J Spots Medicine first published on September 12, 2005 as doi:10.1177/0363546505278304
  11. Shen W, Li Y, Tang Y, Cummins J, Huard J. NS398, a cylooxygenase-2 specific inhibitor, delayed skeletal muscle healing by decreaseing regneration and promoting fibrosis. American J Pathology 2005;167:(4): 1105-1117.
  12. Shen W, Prisk V, Li Y, Foster W, Cummins J, Fu F, Huard J. Inhibited skeletal muscle healing in cyclooxygenase-2 gene deficiency mice, the roles of PGE2 and PGF2a in myofiber fusion. J App Physiol 2006 (June 15, 2006 online print)
  13. Li Y, Li J, Foster W, Tang Y, Xiao X, Huard J. Decorin promotes muscle cell differentiation and muscle regeneration. Molecular Therapy (Accepted) 2007.
  14. Matsuura T, Li Y, Giacobino JP, Fu FH, Huard J. Fast to slow myofiber type conversion during repair of mouse soleus: relationship between myofiber type conversion and PGC-1 expression. Journal of Orthopaedic Research. (Accepted) 2007.
  15. Bedair H, Liu TT, Kaar J, Shown B, Russell A, Huard J, Li Y. Matrix Metalloproteinase (MMP) Therapy Improves Muscle Healing. Journal of Applied Physiology (Accepted) 2007.
  16. Zhu JH*, Li Y*, Shen W, Qiao CP, Ambrosio F, Lavasani M, Nozaki M, Branca MF, Huard J. Relationships between TGF- 1, Myostatin, and decorin: Implications for skeletal muscle fibrosis. J Bio Chem (Accepted) 2007. *First two authors equally contributed to this paper.



 

University of Pittsburgh
School of Medicine