Vanderbilt University School of Medicine

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

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