The School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign

Our laboratory is primarily interested in signaling mechanisms that underlie fundamental cellular and developmental processes. Specifically, our current efforts are focused on a signaling network – namely, the mammalian target of rapamycin (mTOR) network – that senses the availability of nutrients (such as amino acids), and integrate other types of environmental cues (including growth factors, differentiation inducers, and various types of stress) to control mammalian cell growth and differentiation. More recently, a critical role of mTOR signaling in insulin actions and glucose metabolism, as well as fat metabolism, has been recognized.

The mTOR signaling network was initially characterized by its sensitivity to rapamycin, a bacterial macrolide that has tremendous clinical values. Rapamycin and its analogs have been approved by the FDA three times, as an immunosuppressant to prevent graft rejection after transplantation, an anti-restenosis agent used in angioplasty stenting, and an anti-cancer drug. A clear picture of the molecular circuitry of mTOR signaling will not only advance our understanding of various cellular regulations, but also facilitate the future design and refinement of therapeutic strategies.

As a member of the phosphatidylinositol kinase-related Ser/Thr protein 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. Using mammalian cell culture and transgenic mice as the experimental models, we employ a wide range of experimental approaches from molecular biology, biochemistry, cell biology, to genetics and genomics, to dissect the role of nutrients and mTOR signaling in the regulation of these biological processes: [1] cell growth (mass or size increase), where new components of the mTOR pathway and crosstalks among pathways are being identified; [2] skeletal myogenesis, where distinct mTOR pathways are found to regulate various stages of myoblast differentiation and muscle regeneration; [3] insulin resistance (a major risk factor and a principle defect in type II diabetes), where both established and unexpected mTOR mechanisms contribute to the inhibition of insulin signaling at the cellular level.

Representative Publications

M.-S. Yoon, G. Du, J. M. Backer, M. A. Frohman, & J. Chen, (2011) Class III PI-3-kinase activates phospholipase D in an amino acid-sensing mTORC1 pathway, J. Cell Biol. 195, 435-47. [Abstract]

Y. Ge, M.-S. Yoon, & J. Chen, (2011) Raptor and Rheb negatively regulate skeletal myogenesis through suppression of insulin receptor substrate 1 (IRS1), J. Biol. Chem., 286, 35675-82. [Abstract]

M.-S. Yoon, Y. Sun, E. Arauz, Y. Jiang, & J. Chen, (2011) Phosphatidic Acid Activates Mammalian Target of Rapamycin Complex 1 (mTORC1) Kinase by Displacing FK506 Binding Protein 38 (FKBP38) and Exerting an Allosteric Effect, J. Biol. Chem. 286, 29568-74. [Abstract]

Y. Ge, Y. Sun and J. Chen, (2011) IGF-II is regulated by microRNA125b in skeletal myogenesis, J. Cell Biol. 192, 69-81. [Abstract]

Y. Ge and J. Chen, (2011) MicroRNAs in skeletal myogenesis, Cell Cycle 10, 441. [Abstract]

Y. Sun, Y. Ge, J. Drnevich, Y. Zhao, M. Band and J. Chen, (2010) Mammalian Target of Rapamycin controls microRNA-1 and follistatin in skeletal myogenesis, J. Cell Biol. 189, 1157-69. [Abstract]

J.-H. Kim, M.-S. Yoon and J. Chen, (2009) signal transducer and activator of transcription 3 (STAT3) mediates amino acids-induced insulin resistance through Ser727 phosphorylation, J. Biol. Chem., 284, 35425. [Abstract]

Y. Ge, A.-L. Wu, C. Warnes, J. Liu, C. Zhang, H. Kawasome, N. Terada, M. Boppart, C. J. Schoenherr and J. Chen, (2009) mTOR regulates skeletal muscle regeneration in vivo through kinase-dependent and kinase-independent mechanisms, Am. J. Physiol. Cell. Physiol., 297, 1434. [Abstract]

Y. Sun & J. Chen, (2008) mTOR signaling: PLD takes center stage, Cell Cycle, 7, 20. [Abstract]

Y. Sun, Y. Fang, M.-S. Yoon, C. Zhang, M. Roccio, F. J. Zwartkrause, M. Armstrong, H. A. Brown, & J. Chen, (2008) Phospholipase D1 is an effector of Rheb in the mTOR pathway, Proc. Natl. Acad. Sci. USA, 105, 8286. [Abstract]

M.-S. Yoon & J. Chen, (2008) PLD regulates myoblast differentiation through the mTOR—IGF-II pathway, J. Cell Sci., 121, 282. [Abstract]

J.-H. Kim, J. E. Kim, H.-Y. Liu, W. Cao, & J. Chen, (2008) Regulation of IL-6 induced hepatic insulin resistance by mTOR through the STAT3-SOCS3 pathway, J. Biol. Chem., 283, 708. [Abstract]

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]

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]

J. E. Kim and J. Chen, (2004) Regulation of PPARγ activity by mTOR and amino acids in adipogenesis, Diabetes 53, 2748. [Abstract]

Y. Fang, I.-H. Park, A. Wu, G. Du, P. Huang, M.A. Frohman, S.J. Walker, H.A. Brown, & J. Chen, (2003) PLD1 regulates mTOR signaling and mediates Cdc42 activation of S6K1, Current Biology 13, 2037. [Abstract]

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]

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]

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]

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]

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]

Complete Publications List