Biomedical Research Education & Training
Faculty Member

Brantley-Sieders, Dana M., Ph.D.
Assistant Professor of Medicine

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Phone Number: 615-343-4783

Email Address:

Brantley-Sieders, Dana's picture
Academic history
B.A., Maryville College
Ph.D., Vanderbilt University
Postdoctoral Training, Vanderbilt University
Research Instructor, Vanderbilt University

Office Address   Mailing Address

A-4323 MCN

T-3107A MCN, 1161 21st Avenue South 37232-2363

Research Specialty
Molecular mechanisms that regulate mammary epithelial morphogenesis, breast cancer, and host-tumor interactions

Research Description
Our research program focuses on molecular mechanisms that regulate breast tumor growth, tumor angiogenesis, and host-tumor interactions. Members of the Eph family of receptor tyrosine kinases regulate cell growth/survival, motility, and angiogenic remodeling during embryogenesis. More recently, several members of this family have been linked to tumor progression and neovascularization, including breast cancer.

Overexpression of one family member in particular, EphA2, correlates negatively with overall and recurrence-free survival in breast cancer patients. Our laboratory along with others has linked EphA2 signaling to Erk-dependent growth and Rac-dependent invasion in cell culture and animal models of breast cancer, as well as neovascularization and Herceptin-resistance. Moreover, EphA2 physically and functionally interacts with EGF receptor family members, including EGFR and HER2, in the context of breast cancer. More recently, we found EphA2 expression levels are highest within the Triple negative/basal-like subtype of breast cancer. Thus, EphA2 represents a new molecular target for cancer therapy, especially given its simultaneous influence on both tumor cells and the blood vessels within the surrounding microenvironment.

Ongoing studies in the laboratory focus on:

1. The role of EphA2 ligand-independent signaling in lipid metabolism in the context of breast cancer
2. The role of EphA2 signaling in Triple Negative/basal-like breast cancer growth and invasion
3. The role of EphA2 in angiocrine-mediated breast cancer growth and invasion

Amato KR, Wang S, Hastings AK, Youngblood VM, Santapuram PR, Chen H, Cates JM, Colvin DC, Ye F, Brantley-Sieders DM, Cook RS, Tan L, Gray NS, Chen J.. Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC.. J Clin Invest, 124(May 1 (5)), 2037-49, 2014

Song, W, Ma, Y, Wang, J, Brantley-Sieders, D, Chen, J. JNK signaling mediates EPHA2-dependent tumor cell proliferation, motility, and cancer stem cell-like properties in non-small cell lung cancer. Cancer Res, 74(9), 2444-54, 2014

Stanford JC, Young C, Hicks D, Owens P, Williams A, Vaught DB, Morrison MM, Lim J, Williams M, Brantley-Sieders DM, Balko JM, Tonetti D, Earp HS 3rd, Cook RS.. Efferocytosis produces a prometastatic landscape during postpartum mammary gland involution.. J Clin Invest(Sept 24), doi: 10.1172/JCI76375. [Epub ahead of print], 2014

Brantley-Sieders, DM. Clinical relevance of Ephs and ephrins in cancer: lessons from breast, colorectal, and lung cancer profiling. Semin Cell Dev Biol, 23(1), 102-8, 2012

Brantley-Sieders, DM, Fan, KH, Deming-Halverson, SL, Shyr, Y, Cook, RS. Local breast cancer spatial patterning: a tool for community health resource allocation to address local disparities in breast cancer mortality. PLoS One, 7(9), e45238, 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, 104(15), 1182-97, 2012

Brantley-Sieders, DM, Dunaway, CM, Rao, M, Short, S, Hwang, Y, Gao, Y, Li, D, Jiang, A, Shyr, Y, Wu, JY, Chen, J. Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of Slit2 tumor suppressor function in endothelium. Cancer Res, 71(3), 976-87, 2011

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

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, 31(3), 404-16, 2011

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

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

Li, B, Vincent, A, Cates, J, Brantley-Sieders, DM, Polk, DB, Young, PP. Low levels of tumor necrosis factor alpha increase tumor growth by inducing an endothelial phenotype of monocytes recruited to the tumor site. Cancer Res, 69(1), 338-48, 2009

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

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

Fang, WB, Brantley-Sieders, DM, Hwang, Y, Ham, AJ, Chen, J. Identification and functional analysis of phosphorylated tyrosine residues within EphA2 receptor tyrosine kinase. J Biol Chem, 283(23), 16017-26, 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

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

Chen, J, Hicks, D, Brantley-Sieders, D, Cheng, N, McCollum, GW, Qi-Werdich, X, Penn, J. Inhibition of retinal neovascularization by soluble EphA2 receptor. Exp Eye Res, 82(4), 664-73, 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

Tang, T, Shi, Y, Opalenik, SR, Brantley-Sieders, DM, Chen, J, Davidson, JM, Brandt, SJ. Expression of the TAL1/SCL transcription factor in physiological and pathological vascular processes. J Pathol, 210(1), 121-9, 2006

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, 24(53), 7859-68, 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, DM, Caughron, J, Hicks, D, Pozzi, A, Ruiz, JC, Chen, J. 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, DM, Chen, J. Eph receptor tyrosine kinases in angiogenesis: from development to disease. Angiogenesis, 7(1), 17-28, 2004

Schneider, C, Strayhorn, WD, Brantley, DM, Nanney, LB, Yull, FE, Brash, AR. Upregulation of 8-lipoxygenase in the dermatitis of IkappaB-alpha-deficient mice. J Invest Dermatol, 122(3), 691-8, 2004

Muraoka, RS, Koh, Y, Roebuck, LR, Sanders, ME, Brantley-Sieders, D, Gorska, AE, Moses, HL, Arteaga, CL. Increased malignancy of Neu-induced mammary tumors overexpressing active transforming growth factor beta1. Mol Cell Biol, 23(23), 8691-703, 2003 PMCID:262670

Brantley, DM, Cheng, N, Thompson, EJ, Lin, Q, Brekken, RA, Thorpe, PE, Muraoka, RS, Cerretti, DP, Pozzi, A, Jackson, D, Lin, C, Chen, J. Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene, 21(46), 7011-26, 2002

Cheng, N, Brantley, DM, Chen, J. The ephrins and Eph receptors in angiogenesis. Cytokine Growth Factor Rev, 13(1), 75-85, 2002

Cheng, N, Brantley, DM, Liu, H, Lin, Q, Enriquez, M, Gale, N, Yancopoulos, G, Cerretti, DP, Daniel, TO, Chen, J. Blockade of EphA receptor tyrosine kinase activation inhibits vascular endothelial cell growth factor-induced angiogenesis. Mol Cancer Res, 1(1), 2-11, 2002

Muraoka, RS, Dumont, N, Ritter, CA, Dugger, TC, Brantley, DM, Chen, J, Easterly, E, Roebuck, LR, Ryan, S, Gotwals, PJ, Koteliansky, V, Arteaga, CL. Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest, 109(12), 1551-9, 2002 PMCID:151012

Muraoka, RS, Lenferink, AE, Law, B, Hamilton, E, Brantley, DM, Roebuck, LR, Arteaga, CL. ErbB2/Neu-induced, cyclin D1-dependent transformation is accelerated in p27-haploinsufficient mammary epithelial cells but impaired in p27-null cells. Mol Cell Biol, 22(7), 2204-19, 2002 PMCID:133673

Brantley, DM, Chen, CL, Muraoka, RS, Bushdid, PB, Bradberry, JL, Kittrell, F, Medina, D, Matrisian, LM, Kerr, LD, Yull, FE. Nuclear factor-kappaB (NF-kappaB) regulates proliferation and branching in mouse mammary epithelium. Mol Biol Cell, 12(5), 1445-55, 2001 PMCID:34596

Bushdid, PB, Chen, CL, Brantley, DM, Yull, F, Raghow, R, Kerr, LD, Barnett, JV. NF-kappaB mediates FGF signal regulation of msx-1 expression. Dev Biol, 237(1), 107-15, 2001

Muraoka, RS, Lenferink, AE, Simpson, J, Brantley, DM, Roebuck, LR, Yakes, FM, Arteaga, CL. Cyclin-dependent kinase inhibitor p27(Kip1) is required for mouse mammary gland morphogenesis and function. J Cell Biol, 153(5), 917-32, 2001 PMCID:2174338

Brantley, DM, Yull, FE, Muraoka, RS, Hicks, DJ, Cook, CM, Kerr, LD. Dynamic expression and activity of NF-kappaB during post-natal mammary gland morphogenesis. Mech Dev, 97(1-2), 149-55, 2000

Muraoka, RS, Bushdid, PB, Brantley, DM, Yull, FE, Kerr, LD. Mesenchymal expression of nuclear factor-kappaB inhibits epithelial growth and branching in the embryonic chick lung. Dev Biol, 225(2), 322-38, 2000

Bushdid, PB, Brantley, DM, Yull, FE, Blaeuer, GL, Hoffman, LH, Niswander, L, Kerr, LD. Inhibition of NF-kappaB activity results in disruption of the apical ectodermal ridge and aberrant limb morphogenesis. Nature, 392(6676), 615-8, 1998

Dana M Brantley. Apolipoprotein E synthesis by transplanted bone marrow derived cells in apolipoprotein E deficient mice. BIOS, 67, 74-82, 1996

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