Honami Naora, Ph.D.
1994, The Australian National University
The University of Texas M. D. Anderson Cancer Center
Department of Systems Biology
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Honami Naora, Ph.D. 1994, The Australian National University The University of Texas M. D. Anderson Cancer Center
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Research Interests:
The research interest of my laboratory is to understand how aberrations of processes that normally control embryonic development contribute to tumorigenesis.
Cancer is increasingly thought to be an aberrant form of organogenesis or development "gone wrong". My laboratory primarily focuses on the role of homeobox genes in cancer. These genes encode transcription factors that control cell differentiation during embryonic development. We are particularly interested in cancers of female reproductive organs, because these organs exhibit dynamic developmental plasticity. We have found that the histogenesis of the major subtypes of ovarian cancer involves inappropriate activation of developmental programs that are regulated by members of the HOX family of homeobox genes. These findings are significant, because we identified a repertoire of genes that control the type and degree of tumor differentiation which are key determinants of clinical behavior and prognosis. Our ongoing work focuses on studying the mechanisms of these and other homeobox genes in ovarian cancer and in other types of cancer.
Homeobox genes, like many other regulators of embryonic patterning, are conserved throughout evolution. Thus, studies of embryonic development in lower organisms can provide significant insight into the molecular underpinnings of human cancers. Border cell migration is a process that normally occurs during ovarian development in Drosophila in which epithelial cells invade neighboring tissue. Because of the intriguing similarity in behavior of border cells and of cancer cells, we have been utilizing genetic analysis of border cell migration in Drosophila as a novel approach to identify related molecules that control cancer metastasis.
The studies in my laboratory are multi-disciplinary and integrate cancer biology with developmental biology. The projects include molecular analysis of transcriptional regulation, studies of cell differentiation and cell-cell interactions, development of animal models to study cell transformation and tumor progression, and translational studies relating to diagnosis and identification of therapeutic targets.
Selected Publications:
Hara F, Samuel S, Liu J, Rosen D, Langley R, Naora H (2007) A homeobox gene related to Drosophila Distal-less promotes ovarian tumorigenicity by inducing expression of vascular endothelial growth factor and fibroblast growth factor-2. Am J Pathol 170: 1595-1606.
Yoshida H, Broaddus R, Cheng W, Xie, S, Naora H (2006) Deregulation of the HOXA10 homeobox gene in endometrial carcinoma: Role in epithelial-mesenchymal transition. Cancer Res 66: 889-97.
Cheng W, Liu J, Yoshida H, Rosen D, Naora H (2005). Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract. Nat Med 11: 531-7.
Yoshida H, Liu J, Samuel S, Cheng W, Rosen D, Naora H (2005) Steroid receptor coactivator-3, a homologue of Taiman that controls cell migration in the Drosophila ovary, regulates migration of human ovarian cancer cells. Mol Cell Endocrinol 245:77-85.