jchen@life.uiuc.edu
C526 CLSL
Office: (217) 265-0674
Lab: (217) 265-0672
Fax: (217) 265-0674
Mail to:
Dept. of Cell and Developmental Biology
University of Illinois
B107 CLSL
601 S. Goodwin Avenue
Urbana, IL 61801
Jie Chen
Associate Professor of Cell and Developmental Biology
Education
B.S., Peking University, China (Biology)
Ph.D., Rice University (Biochemistry)
Postdoc., Harvard University
Teaching Interests
Signal Transduction mechanisms in mammalian cell growth, proliferation and differentiation -- the rapamycin-sensitive signaling network
Our laboratory is primarily interested in signaling mechanisms that regulate fundamental cellular processes in mammals such as growth, proliferation and differentiation. Specifically, our current efforts are focused on the rapamycin-sensitive signaling network that governs a wide range of cellular functions from translation, transcription to anti-apoptosis. Aided by a wide range of experimental approaches from molecular biology, biochemistry, cell biology, to genetics/transgenics and genomics, the major areas of research ongoing in the lab concern the mechanisms of rapamycin-sensitive signaling in cell growth and proliferation, and various types of cellular differentiation.
The bacterial macrolide rapamycin, initially isolated as an anti-fungal agent, has elicited tremendous medical interests due to its multitude of activities. As an FDA-approved immunosuppressant, rapamycin is used to prevent graft rejection after transplantation. In recent years rapamycin has been used in angioplasty stenting to prevent restenosis (re-blockage of arteries after angioplasty procedures) with great efficacy. Furthermore, rapamycin and its analogues are promising anti-cancer drugs, potently inhibiting a wide range of human tumor cell lines and xenografts. A clear picture of the molecular circuitry of the rapamycin-sensitive signaling network will not only advance our understanding of various cellular regulations, but also facilitate the future design and refinement of therapeutic strategies.
A key player in the rapamycin-sensitive signal transduction is the mammalian target of rapamycin - mTOR, a protein conserved from yeast to human. As a member of the phosphatidylinositol kinase-related kinase family, mTOR is a master regulator of a broad spectrum of cellular functions. It has become increasingly evident that mTOR assembles distinct signaling networks in different cellular contexts. The current efforts in our lab focus on dissection of the rapamycin-sensitive signaling in these biological systems: [1] cell growth and proliferation, where new components and crosstalks are being identified; [2] skeletal myogenesis, where distinct mTOR pathways are required for various stages of muscle differentiation and growth; [3] adipogenesis and fat metabolism; [4] insulin resistance (a principle defect in type II diabetes) at the cellular level.
Representative Publications
R. A. Bachmann, J.-H. Kim, A.-L. Wu, I.-H. Park, and J. Chen, (2006) A nuclear transport signal in mammalian target of rapamycin is critical for its cytoplasmic signaling to S6 kinase 1, J. Biol. Chem. 281, 7357. [Abstract] [Article-PDF]
I.-H. Park and J. Chen, (2005) Mammalian Target of Rapamycin (mTOR) Signaling Is Required for a Late-stage Fusion Process during Skeletal Myotube Maturation, J. Biol. Chem. 280, 32009. [Abstract] [Article-PDF]
I.-H. Park, E. Erbay, P. Nuzzi, and J. Chen, (2005) Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1, Exp. Cell Res. 309, 211. [Abstract] [Article-PDF]
J. E. Kim and J. Chen, (2004) Regulation of PPARγ activity by mTOR and amino acids in adipogenesis, Diabetes 53, 2748. [Abstract] [Article-PDF]
Fang, Y., Park, I.-H., Wu, A., Du, G., Huang, P., Frohman, M.A., Walker, S.J., Brown, H.A., and Chen, J. (2003) PLD1 regulates mTOR signaling and mediates Cdc42 activation of S6K1, Current Biology 13, 2037. [Abstract] [Article-PDF]
E. Erbay, I.-H. Park, P. Nuzzi, C.J. Schoenherr, and J. Chen, (2003) IGF-II transcription in skeletal myogenesis is controlled by mTOR and nutrients, J. Cell Biol. 163, 931. [Abstract] [Article-PDF]
Y. Fang, M. Viella-Bach, R. Bachmann, A. Flanigan, and J. Chen, (2001) Phosphatidic acid-mediated mitogenic activation of mTOR signaling, Science 294, 1942. [Abstract] [Article-PDF]
I.-H. Park, R. Bachmann, H. Shirazi and J. Chen, (2002) Regulation of S6 kinase 2 by the mammalian target of rapamycin, J. Biol. Chem. 277, 31423. [Abstract] [Article-PDF]
E. Erbay and J. Chen, (2001) The mammalian target of rapamycin regulates C2C12 myogenesis via a kinase-independent mechanism, J. Biol. Chem. 276, 36079 (Accelerated Publication). [Abstract] [Article-PDF]
J. E. Kim and J. Chen, (2000) Cytoplasmic-nuclear shuttling of FKBP12-rapamycin-associated protein is involved in rapamycin-sensitive signaling and translation initiation, Proc. Natl. Acad. Sci. USA 97, 14340 [Abstract] [Article-PDF]