Jie Chen

Jie Chen

jchen@life.illinois.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
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Professor of Cell and Developmental Biology
Head of Cell and Developmental Biology

Research Topics

Development, Membrane Biology, Metabolic Regulation, Protein Structure, RNA Biology, Signal Transduction

Education

B.S., Peking University, China (Biology)
Ph.D., Rice University (Biochemistry)
Postdoc., Harvard University

Signal Transduction in Mammalian Cell Growth and Differentiation

Our laboratory is interested in understanding signal transduction mechanisms that underlie fundamental cellular and developmental processes in mammals. We employ a wide range of experimental approaches including molecular biology, cell biology, biochemistry, single-molecule biophysics, and mouse genetics. Currently we are pursuing the following areas of investigation.

mTOR Signaling Network

The mammalian target of rapamycin (mTOR), a member of the phosphatidylinositol kinase-related Ser/Thr protein kinase family, assembles a signaling network that is a master regulator of cell growth, proliferation, differentiation, and metabolism. The mTOR network senses the availability of nutrients (amino acids, in particular), and integrates other types of environmental cues, including growth factors, cellular energy levels, and various types of stress. Rapamycin, an exquisitely specific inhibitor for mTOR, is a bacterial macrolide that has tremendous clinical values. Rapamycin and its analogs have been approved by the FDA for three types of clinical use – as an immunosuppressant to prevent graft rejection after transplantation, an anti-restenosis agent used in angioplasty stenting, and an anti-cancer drug. Furthermore, the anti-aging effects of rapamycin have been well established in many organisms including rodents. Our biochemical, biophysical, and biological investigations continue to uncover regulators, pathways, and regulatory mechanisms in the mTOR signaling network. These efforts will not only advance our understanding of cellular regulation, but also facilitate the future design and improvement of therapeutic strategies.

Skeletal Muscle Regeneration

The adult skeletal muscle has a tremendous capacity for repair and regeneration upon injury. Another major focus in our lab is to understand the signal transduction mechanisms governing skeletal muscle regeneration. Using mouse models for injury-induced muscle regeneration complemented with in vitro experimental systems of myoblast differentiation, we interrogate the molecular wiring that controls the highly coordinated cellular events leading to the formation of multi-nucleated myofibers. Our findings have revealed a central role of mTOR in assembling pathways that regulate various stages of myogenesis, distinct from those that control cell growth. In addition, we have dissected the mechanisms of regulation by myogenic microRNAs. Our current efforts are also focused on myocyte-secreted cytokines and their signaling that critically contribute to myogenic differentiation in vitro and muscle regeneration in vivo. Knowledge gained may lead to potential future therapeutic targets for boosting adult muscle regenerative capacity and for treating aging- or disease-related muscular atrophy and dystrophy.

Lipid-Protein Interactions

Some phospholipids in the cell membrane play important regulatory roles rather than serving structural purposes, and these signaling lipids interact with proteins to effect the regulation. Revealing the specificity of lipid-protein interactions is pivotal to the understanding of lipid signaling, and a critical need is experimental approaches that enable investigation of such interactions in physiologically relevant contexts. In collaboration with Taekjip Ha Laboratory (Johns Hopkins University) we have recently developed a single-molecule pulldown (SiMPull) assay to study the interaction between lipid vesicles and proteins of interest in crude cell lysates with high sensitivity and specificity. We have also adopted a microscale thermophoresis (MST) assay to rapidly assess lipid binding by proteins in cell lysates. Taking advantage of these new assays we are re-evaluating phosphoinositide binding by PH domain-containing proteins, the largest family of putative lipid binding proteins in the human genome. Our results to date have already revealed a striking lipid binding specificity not previously appreciated. Further investigation of such interactions will likely yield novel biological insights.

Awards

Faculty Excellence Award, School of Molecular and Cellular Biology, University of Illinois, 2011
University Scholar, University of Illinois, 2007
American Cancer Society Research Scholar, 2003 - 2007
NIH Shannon Award for New Investigators, 1998
Irvington Institute of Immunology Fellow, 1994 - 1997

Representative Publications

D. Dutta, K.-Y. Lai, A. Reyes-Ordoñez, J. Chen*, and W. A. van der Donk*, (2018) Lanthionine synthetase C-like protein 2 (LanCL2) isimportant for adipogenic differentiation. J. Lipid. Res. 59, 1433-45. [Abstract]

Y. Fang, C. M. Hill, J. Darcy, A. Reyes-Ordoñez, E. Arauz, S. McFadden, C. Zhang, J. Osland, J. Gao, T. Zhang, S. J. Frank, M. A. Javors, R. Yuan, J. J. Kopchick, L. Y. Sun, J. Chen, and A. Bartke, (2018) Effects of rapamycin on growth hormone receptor knockout mice. Proc Natl Acad Sci USA. 2018 Jan 29. pii: 201717065. doi: 10.1073/pnas.1717065115. [Abstract]

C. L. Rosenberger and J. Chen, (2018) To grow or not to grow: TOR and SnRK2 coordinate growth and stress response in Arabidopsis. Molecular Cell 69, 3-4. [Abstract] [full_text]

Z. S. Mahmassani, K. Son, Y. Pincu, M. Munroe, J. Drnevich, J. Chen, M. D. Boppart, (2017) α7β1 Integrin regulation of gene transcription in skeletal muscle following an acute bout of eccentric exercise, Am. J. Physiol. Cell Physiol., 312, C638-C650. [Abstract]

A. Arif, F. Terenzi, A. A. Potdar, J. Jia, J. Sacks, A. China, D. Halawani, K. Vasu, X. Li, J. M. Brown, J. Chen, S. C. Kozma, G. Thomas. and P. L. Fox, (2017) EPRS is a critical mTORC1-S6K1 effector that influences adiposity in mice. Nature, 542, 357-361. [Abstract]

R. J. Waldemer-Streyer, A. Reyes-Ordoñez, D. Kim, R. Zhang, and J. Chen, (2017) Cxcl14 depletion accelerates skeletal myogenesis by promoting cell cycle withdrawal, NPJ Regenerative Medicine, 2, 16017. [Abstract]

C. He, M. Zeng, D. Dutta, T. H. Koh, J. Chen*, and W. A. van der Donk*, (2017) LanCL proteins are not Involved in Lanthionine Synthesis in Mammals, Sci. Rep., 7, 40980. [Abstract]

M.-S. Yoon, K. Son, E. Arauz, J. M. Han, S. Kim, and J. Chen, (2016) Leucyl-tRNA synthetase activates Vps34 in amino acid-sensing mTORC1 signaling, Cell Rep 16, 1510-17. [Abstract]

E. Arauz, V. Aggarwal, A. Jain, T. Ha*, and J. Chen*, (2016) Single-Molecule Analysis of Lipid-Protein Interactions in Crude Cell Lysates, Anal. Chem., 88, 4269-76. [Abstract]

R. J. Waldemer-Streyer and J. Chen, (2015) Myocyte-derived Tnfsf14 is a survival factor necessary for myoblast differentiation and skeletal muscle regeneration, Cell Death & Disease, 6, e2026. [Abstract]

M.-S. Yoon, C.L. Rosenberger, C. Wu, N. Truong, J.V. Sweedler, and J. Chen, (2015) Rapid mitogenic regulation of the mTORC1 inhibitor, DEPTOR, by phosphatidic acid, Mol. Cell, 58, 549-556. [Abstract]

A. Jain, E. Arauz, V. Aggarwal, N. Ikon, J. Chen*, and T. Ha*, Stoichiometry and assembly of mTOR complexes revealed by single-molecule pulldown, Proc. Natl. Acad. Sci. USA (direct submission); published ahead of print December 1, 2014. [Abstract]

M. Zeng, W. A. van der Donk*, J. Chen*, (2014) Lanthionine synthetase C-like protein 2 (LanCL2) is a novel regulator of Akt, Mol. Biol. Cell, 25, 3954-61. [Abstract]

M.-S. Yoon and J. Chen, (2013) Distinct amino acid-sensing mTOR pathways regulate skeletal myogenesis, Mol. Biol. Cell, 24, 3754-63. [Abstract]

N. Khanna, Y. Fang, M.-S. Yoon, and J. Chen, (2013) XPLN is an endogenous inhibitor of mTORC2. Proc. Natl. Acad. Sci. USA, 110, 15979-84. (direct submission) [Abstract]

M.-S. Yoon, C. Zhang, Y. Sun, C. J. Schoenherr, and J. Chen, (2013) Mechanistic target of rapamycin controls homeostasis of adipogenesis, J. Lipid Res., 54, 2166-73.[Abstract]

Y. Ge, R. J. Waldemer, R. Nalluri, P. D. Nuzzi, and J. Chen, (2013) RNAi screen reveals potentially novel roles of cytokines in myoblast differentiation, PLoS One, 8, e68068.[Abstract]

Y. Ge, R. J. Waldemer, R. Nalluri, P. D. Nuzzi, and J. Chen, (2013) Flt3L is a novel regulator of skeletal myogenesis, J. Cell Sci., 126, 3370-9.[Abstract]

Y. Ge and J. Chen, (2012) mTOR signaling network in skeletal myogenesis, J. Biol. Chem. 287, 43928-35.[Abstract]

C. Zhang, A. A. Wendel, M. R. Keogh, T. E. Harris, J. Chen, and R. A. Coleman, (2012) Glycerolipid signals alter mTORC2 to diminish insulin signaling, Proc. Natl. Acad. Sci. USA, 109, 1667-72.[Abstract]

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]

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