Biomedical Research Education & Training
Faculty Member

Chen, Jin, M.D., Ph.D.
Professor of Medicine
Professor of Cell and Developmental Biology
Professor of Cancer Biology

Lab Url: N/A

Phone Number: 615-343-3819

Email Address: jin.chen@vanderbilt.edu

Chen, Jin's picture
Academic history
M.D., Shanghai Medical University, China
Ph.D., Harvard University, Boston, MA
Post-doc , Massachusetts Institute of Technology
Post-doc, Vanderbilt University

Office Address   Mailing Address

T-3207E Medical Center North

T-3207E MCN Vanderbilt University School of Medicine 37232


Research Keywords
Receptor tyrosine kinase, signal transduction, cancer metabolism, cancer stem cell, tumor angiogenesis.

Research Specialty
To investigate the role of a new family of receptor tyrosine kinase (RTK), the Eph receptors and their ligands ephrins, in tumor angiogenesis, tumor metabolism, and cancer stem cells.

Research Description
Our major focus has been to characterize the role of a new family of receptor tyrosine kinase (RTK), the Eph receptors and their ligands ephrins, in tumor metabolism, cancer metastasis, and tumor angiogenesis. Our approach involves a combination of oncogenomics and proteomics, confocal microscopy and imaging, transgenic and knock out animal models, and traditional cell biology and biochemistry techniques.

Eph RTKs and their ligands are dysregulated in tumor tissues and expression of these molecules is associated with clinical outcome of various cancer type. In particular, EphA2 receptor plays critical roles in both tumor cells and tumor blood vessels. Our laboratory demonstrated that epithelial EphA2 is required for cell proliferation and tumor initiation. We also showed that vascular endothelial EphA2 promotes tumor progression through angiogenesis. As EphA2 regulates both tumor cells and host microenvironment, it is a good target for cancer therapy. Several anti-EphA2 agents have been developed and we are testing selective small molecule Eph receptor kinase inhibitors. Current projects in the lab include:

1. Role of ephrin-A1, the ligand for EphA2 RTK, in tumor metabolism in breast cancer.
2. EphA2 in K-Ras and TKI-resistant EGFR mutant lung cancer and cancer stem cells.
3. Dissecting opposing roles of EphA2 and EphA3 in lung cancer.
4. Regulation of angiocrine signaling in tumor progression, metastasis, and stem cell function.




Publications
Amato KR, Wang S, Hasting AK, Youngblood VM, Santapuram, PR, Chen H, Cates, JM, Colvin DC, Ye F, Brantley-Sieders DM, Cook RS, Li T, Gray N, and Chen J. Genetic and pharmacologic inhibition of EphA2 induces apoptosis in NSCLC. J Clinc Invest, (in press), 2014

Song W, Gong Y, Wang J, Brantley-Sieders D, and Chen J. JNK singnaling mediates EphA2-dependent tumor malignancy and cancer stem cell-like properties in non-small cell lung cancer. Cancer Res, (in press), 2014

Boissier, P, Chen, J, Huynh-Do, U. EphA2 Signaling Following Endocytosis: Role of Tiam1. Traffic, 14(12), 1255-71, 2013

Chen, J. Regulation of tumor initiation and metastatic progression by eph receptor tyrosine kinases. Adv Cancer Res, 114, 1-20, 2012

Funk, SD, Yurdagul, A, Albert, P, Traylor, JG, Jin, L, Chen, J, Orr, AW. EphA2 activation promotes the endothelial cell inflammatory response: a potential role in atherosclerosis. Arterioscler Thromb Vasc Biol, 32(3), 686-95, 2012

Hahn, AS, Kaufmann, JK, Wies, E, Naschberger, E, Panteleev-Ivlev, J, Schmidt, K, Holzer, A, Schmidt, M, Chen, J, K??nig, S, Ensser, A, Myoung, J, Brockmeyer, NH, St??rzl, M, Fleckenstein, B, Neipel, F. The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi''s sarcoma-associated herpesvirus. Nat Med, 2012

Lee, K, Nam, KT, Cho, SH, Gudapati, P, Hwang, Y, Park, DS, Potter, R, Chen, J, Volanakis, E, Boothby, M. Vital roles of mTOR complex 2 in Notch-driven thymocyte differentiation and leukemia. J Exp Med, 209(4), 713-28, 2012

Rao, M, Song, W, Jiang, A, Shyr, Y, Lev, S, Greenstein, D, Brantley-Sieders, D, Chen, J. VAMP-associated protein B (VAPB) promotes breast tumor growth by modulation of Akt activity. PLoS One, 7(10), e46281, 2012

Zhuang, G, Song, W, Amato, K, Hwang, Y, Lee, K, Boothby, M, Ye, F, Guo, Y, Shyr, Y, Lin, L, Carbone, DP, Brantley-Sieders, DM, Chen, J. Effects of Cancer-Associated EPHA3 Mutations on Lung Cancer. J Natl Cancer Inst, 2012

Brantley-Sieders, DM, Jiang, A, Sarma, K, Badu-Nkansah, A, Walter, DL, Shyr, Y, Chen, J. Eph/ephrin profiling in human breast cancer reveals significant associations between expression level and clinical outcome. PLoS One, 6(9), e24426, 2011 PMCID:3174170

Brantley-Sieders, DM, Dunaway, CM, Rao, M, Short, S, Hwang, Y, Gao, Y, Li, D, Jiang, A, Shyr, Y, Wu, DJ, Chen, J. Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of Slit2 tumor suppressor function in endothelium. Cancer Res, 2010

Dunaway, CM, Hwang, Y, Lindsley, CW, Cook, RS, Wu, JY, Boothby, M, Chen, J, Brantley-Sieders, DM. Cooperative Signaling Between Slit2 and Ephrin-A1 Regulates a Balance Between Angiogenesis and Angiostasis. Mol Cell Biol, 2010

Frieden, LA, Townsend, TA, Vaught, DB, Delaughter, DM, Hwang, Y, Barnett, JV, Chen, J. Regulation of heart valve morphogenesis by Eph receptor ligand, ephrin-A1. Dev Dyn, 239(12), 3226-34, 2010

Min, Y, Ren, X, Vaught, DB, Chen, J, Donnelly, E, Lynch, CC, Lin, PC. Tie2 signaling regulates osteoclastogenesis and osteolytic bone invasion of breast cancer. Cancer Res, 70(7), 2819-28, 2010 PMCID:2848896

Zhuang, G, Brantley-Sieders, DM, Vaught, D, Yu, J, Xie, L, Wells, S, Jackson, D, Muraoka-Cook, R, Arteaga, C, Chen, J. Elevation of receptor tyrosine kinase EphA2 mediates resistance to trastuzumab therapy. Cancer Res, 70(1), 299-308, 2010

Bogan, C, Chen, J, O''Sullivan, MG, Cormier, RT. Loss of EphA2 receptor tyrosine kinase reduces ApcMin/+ tumorigenesis. Int J Cancer, 124(6), 1366-71, 2009 PMCID:2682598

Brantley-Sieders, DM, Zhuang, G, Vaught, D, Freeman, T, Hwang, Y, Hicks, D, Chen, J. Host deficiency in Vav2/3 guanine nucleotide exchange factors impairs tumor growth, survival, and angiogenesis in vivo. Mol Cancer Res, 7(5), 615-23, 2009 PMCID:2739740

Vaught, D, Chen, J, Brantley-Sieders, DM. Regulation of mammary gland branching morphogenesis by EphA2 receptor tyrosine kinase. Mol Biol Cell, 20(10), 2572-81, 2009 PMCID:2682598

Brantley-Sieders, DM, Zhuang, G, Hicks, D, Fang, WB, Hwang, Y, Cates, JM, Coffman, K, Jackson, D, Bruckheimer, E, Muraoka-Cook, RS, Chen, J. The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling. J Clin Invest, 118(1), 64-78, 2008 PMCID:2129239

Chen, J, Zhuang, G, Frieden, L, Debinski, W. Eph receptors and Ephrins in cancer: common themes and controversies. Cancer Res, 68(24), 10031-3, 2008 PMCID:2605675

Fang, WB, Brantley-Sieders, DM, Hwang, Y, Ham, A, Chen, J. Identification and functional analysis of phosphorylated tyrosine residues within EphA2 receptor tyrosine kinase. J Biol Chem, 2008 PMCID:2414276

Fang, WB, Ireton, RC, Zhuang, G, Takahashi, T, Reynolds, A, Chen, J. Overexpression of EPHA2 receptor destabilizes adherens junctions via a RhoA-dependent mechanism. J Cell Sci, 121(Pt 3), 358-68, 2008

Vaught, D, Brantley-Sieders, DM, Chen, J. Eph receptors in breast cancer: roles in tumor promotion and tumor suppression. Breast Cancer Res, 10(6), 217, 2008 PMCID:2656900

Zhuang, G, Hunter, S, Hwang, Y, Chen, J. Regulation of EphA2 receptor endocytosis by SHIP2 lipid phosphatase via phosphatidylinositol 3-Kinase-dependent Rac1 activation. J Biol Chem, 282(4), 2683-94, 2007

Brantley-Sieders, DM, Fang, WB, Hwang, Y, Hicks, D, Chen, J. Ephrin-A1 facilitates mammary tumor metastasis through an angiogenesis-dependent mechanism mediated by EphA receptor and vascular endothelial growth factor in mice. Cancer Res, 66(21), 10315-24, 2006

Hunter, SG, Zhuang, G, Brantley-Sieders, D, Swat, W, Cowan, CW, Chen, J. Essential role of Vav family guanine nucleotide exchange factors in EphA receptor-mediated angiogenesis. Mol Cell Biol, 26(13), 4830-42, 2006 PMCID:1489141

Brantley-Sieders, DM, Fang, WB, Hicks, DJ, Zhuang, G, Shyr, Y, Chen, J. Impaired tumor microenvironment in EphA2-deficient mice inhibits tumor angiogenesis and metastatic progression. FASEB J, 19(13), 1884-6, 2005

Fang, WB, Brantley-Sieders, DM, Parker, MA, Reith, AD, Chen, J. A kinase-dependent role for EphA2 receptor in promoting tumor growth and metastasis. Oncogene, 2005

Ireton, RC, Chen, J. EphA2 receptor tyrosine kinase as a promising target for cancer therapeutics. Curr Cancer Drug Targets, 5(3), 149-57, 2005

Brantley-Sieders, D, Parker, M, Chen, J. Eph receptor tyrosine kinases in tumor and tumor microenvironment. Curr Pharm Des, 10(27), 3431-42, 2004

Brantley-Sieders, Dana M, Caughron, Justin, Hicks, Donna, Pozzi, Ambra, Ruiz, Joseph C, Chen, Jin. EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation. J Cell Sci, 117(Pt 10), 2037-49, 2004

Brantley-Sieders, Dana M, Chen, Jin. Eph receptor tyrosine kinases in angiogenesis: from development to disease. Angiogenesis, 7(1), 17-28, 2004

Brantley, Dana M, Cheng, Nikki, Thompson, Erin J, Lin, Qing, Brekken, Rolf A, Thorpe, Philip E, Muraoka, Rebecca S, Cerretti, Douglas Pat, Pozzi, Ambra, Jackson, Dowdy, Lin, Charles, Chen, Jin. Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene, 21(46), 7011-26, 2002

Cheng, Nikki, Brantley, Dana M, Chen, Jin. The ephrins and Eph receptors in angiogenesis. Cytokine Growth Factor Rev, 13(1), 75-85, 2002

Muraoka, Rebecca S, Dumont, Nancy, Ritter, Christoph A, Dugger, Teresa C, Brantley, Dana M, Chen, Jin, Easterly, Evangeline, Roebuck, L Renee, Ryan, Sarah, Gotwals, Philip J, Koteliansky, Victor, Arteaga, Carlos L. Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest, 109(12), 1551-9, 2002 PMCID:151012

Cheng, N, Chen, J. Tumor necrosis factor-alpha induction of endothelial ephrin A1 expression is mediated by a p38 MAPK- and SAPK/JNK-dependent but nuclear factor-kappa B-independent mechanism. J Biol Chem, 276(17), 13771-7, 2001

Chen, J, Ruley, H E. An enhancer element in the EphA2 (Eck) gene sufficient for rhombomere-specific expression is activated by HOXA1 and HOXB1 homeobox proteins. J Biol Chem, 273(38), 24670-5, 1998

Chen, J, Nachabah, A, Scherer, C, Ganju, P, Reith, A, Bronson, R, Ruley, H E. Germ-line inactivation of the murine Eck receptor tyrosine kinase by gene trap retroviral insertion. Oncogene, 12(5), 979-88, 1996


Postdoctoral Position Available
Yes

Postdoctoral Position Details
A postdoctoral position is available for study the interaction between EphA2 RTK and Ras proteins in lung cancer. Recent PhDs who are US citizens or permanent residents are encouraged to apply. Please send CV and the contact information of three referees to jin.chen@vanderbilt.edu.

Updated Date
04/02/2014