Dr. Valerie Odero Marah
Department of Biological Sciences
Clark Atlanta University
Free University of Brussels, Brussels, Belgium, MS, 1991-93, Molecular Biology, University of Iowa, Iowa City, Iowa; PhD, 1998-2003, Molecular Biology; Emory University, Atlanta, Georgia, Postdoctoral, 2003-2006, Cancer Biology
Epithelial-mesenchymal transition (EMT) occurs during normal embryonic development and epithelial tumor progression. Several factors such as Snail transcription factor, are associated with EMT, and contribute to motility, invasion, and angiogenesis. Understanding the factors that contribute to EMT and prostate cancer metastasis is crucial for development of cancer therapies. My laboratory focuses on the role of Snail transcription factor in prostate cancer progression and metastasis utilizing different prostate cancer cell lines.
With funding from NIH P20, we have found that Snail-induced EMT in prostate cancer cells involves reactive oxygen species (ROS) and receptor activator of NFB (RANKL), two factors that are important in cancer disease progression and bone metastatic lesions, respectively. Additionally, we have found that antioxidants can reverse the effects of Snail-mediated EMT in vitro. This research was presented at the Gordon Research Conference, 2010 DNA Damage, Mutation & Cancer, from March 21-26, 2010, and earned a ‘Carl Underrepresented Minority Fellowship’. These studies are in collaboration with investigators at Emory University, Howard University and Geogia Institute of Technology.
Additionally, with funding from Department of Defense (DOD) New Investigator Award, we have shown that Snail induces neuroendocrine differentiation, a process by which cancer cells promote growth of neighboring cancer cells and thus sustain tumor growth. These results were presented at the American Association for Cancer Research (AACR) 100th annual meeting, and earned a ‘Minority in Cancer Research Fellowship’, and recognition for being the top 3-4% of abstracts presented at the meeting. These results are also published in the peer-reviewed ‘Prostate’ journal in the February 2010 issue. We are currently collaborating with investigators from University of Washington to look at Snail expression in neuroendocrine tumors from human patients. We are also characterizing the signaling pathway of Snail-induced EMT, and continuing with examination of the effect of antagonizing Snail expression on tumor aggressiveness in vitro and in vivo. We believe these studies will identify Snail as an attractive therapeutic target not only for EMT during primary tumor progression but also for bone metastatic lesions at the secondary site.
Dawn A. Kirschmann, Ruth A. Lininger, Lynn M. Gardner, Elisabeth A. Seftor, Valerie A. Odero, Alexandra M. Ainsztein, William C. Earnshaw, Lori L. Wallrath, and Mary J.C. Hendrix. 2000. Down-Regulation of HP1Hsa expression is associated with the metastatic phenotype in breast cancer. Cancer Research 60: 3359-3363.
Valerie A. Odero-Marah, Zhila Khalkhali-Ellis, Galen B. Schneider, Elisabeth A. Seftor, Richard E.B. Seftor, John G. Koland, and Mary J.C. Hendrix. 2002. Tyrosine phosphorylation of maspin in normal mammary epithelia and breast cancer cells. Biochemical and Biophysical Research Communications 295: 800-805.
Valerie A. Odero-Marah, Zhila Khalkhali-Ellis, Jirapat Chunthapong, Sumaira Amir, Richard E.B. Seftor, Elisabeth A. Seftor, and Mary J.C. Hendrix. 2003. Maspin Regulates Different Signaling Pathways for Motility and Adhesion in Aggressive Breast Cancer Cells. Cancer Biol Ther 2:398-403, 2003.
Amir S, Margaryan NV, Odero-Marah V, Khalkhali-Ellis Z, Hendrix MJ. Maspin Regulates Hypoxia-Mediated Stimulation of uPA/uPAR Complex in Invasive Breast Cancer Cells. Cancer Biology and Therapy, 4(4), 2005.
Juanchun Xu, Ruoxiang Wang, Zhi Hui Xie, Valerie A. Odero-Marah, Sen Pathak, Asha Multani, Leland W.K. Chung and Haiyen E. Zhau. Prostate Cancer Metastasis: Roles of host microenvironment promoting epithelial to mesenchymal transition and increasing bone and adrenal gland metastases. The Prostate, 66(15): 1664-73, 2006.
Graham TR, Zhau HE, Odero-Marah VA, Osunkoya AO, Kimbro KS, Tighiouart M, Liu T, Simons JW and O’Regan RM. Insulin-like Growth Factor-I Dependent Upregulation of ZEB1 Expression Drives EMT in prostate cancer cells in vitro. Cancer Res 2008; 68(7) 1-10.
Valerie A. Odero-Marah, Jianchun Xu, Haiyen E. Zhau, and Leland W. K. Chung. 2008. Receptor Activator of NF-κB Ligand (RANKL) Expression, Promoted by Growth Factors, Interaction with Bone Microenvironment, and Snail transcription Factor, is Associated with Epithelial to Mesenchymal Transition in Human Prostate Cancer Cells. Cell Research, In Press.
Zhau HE, Odero-Marah V, Lue HW, Nomura T, Wang R, Chu G, Huang WC, and Chung LWK. (2008). Epithelial to Mesenchymal Transition (EMT) in Human Prostate Cancer: Lessons Learned from ARCaP Model. Clinical and Experimental Metastasis. In press.
Graham TR, Odero-Marah VA, Chung LW, Agrawal KC, Abdel-Mageed AB. PI3K/Akt Dependent Transcriptional Regulation and Activation of BMP-2-Smad Signaling by NF-kappaB in Metastatic Prostate Cancer Cells. The Prostate: 2009 Feb 1;69(2):168-80.
Graham TR, Yacoub R, Taliaferro-Smith L, Osunkoya AO, Odero-Marah VA, Liu T, Kimbro KS, Sharma D, O'Regan RM. Reciprocal regulation of ZEB1 and AR in triple negative breast cancer cells. Breast Cancer Res Treat. 2009 Nov 18.
Danielle McKeithen, Tisheeka Graham, Leland W. K. Chung, and Valerie Odero-Marah. Snail Transcription Factor Regulates Neuroendocrine Differentiation in LNCaP Prostate Cancer Cells. The Prostate: 2010, Feb 17. PMC Journal in Process.
Chetram MA, Odero-Marah V, Hinton CV. Loss of PTEN Permits CXCR4-mediated Tumorigenesis through ERK1/2 in Prostate Cancer Cells. Mol. Cancer Res: 2011 Jan;9(1):90-102. Epub 2010 Nov 12.
Barnett P, Arnold RS, Mezencev R, Chung LW, Zayzafoon M, Odero-Marah V. Snail-Mediated Regulation of Reactive Oxygen Species in ARCaP Human Prostate Cancer Cells. Biochem Biophys Res Comm: 2011 Jan 7;404(1):34-9. Epub 2010 Nov 17. PMCID: PMC3021188.
Richard E.B. Seftor, Valerie A. Odero, Elisabeth A. Seftor, and Mary J.C. Hendrix. 2002. Maspin suppresses breast cancer cell invasiveness by modulating integrin expression and function. In: Maspin, edited by M.J.C Hendrix, 84-95 USA: Landes Bioscience Publishers.
Wen-Chin Huang, Valerie Odero-Marah, and Leland W.K. Chung. 2004. Biologic and therapeutic implications of osteomimicry and epithelial-mesenchymal transition (EMT) in prostate cancer. In: Molecular Targeting of Bone Metastasis, edited by Shafaat A. Rabbani. Humana Press Publishers.
Leland W. K. Chung, Wen-Chin Huang, Shian-Ying Sung, Daqing Wu, Valerie Odero-Marah, Shuji Isotani, Takeo Nomura, Katsumi Shigemura, Tohru Miyagi and Haiyen E. Zhau. Stromal-epithelial interaction in prostate cancer progression. Clinical Prostate Cancer. Clin Genitourin Cancer. 2006 Sep;5(2):162-170.