Cell differentiation and patterning Cell transformation Tumor progression and tumor microenvironment Cancers of female reproductive organs
The research mission of my laboratory is to understand how aberrations of processes that normally control embryonic development contribute to tumorigenesis and tumor behavior. 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 normally control developmental patterning, but many are aberrantly expressed in tumors. We are particularly interested in cancers of the female reproductive organs, because these tissues exhibit dynamic developmental plasticity and represent ideal organ systems to study how tumorigenesis is intimately related to embryonic development. By investigating the molecular underpinnings of this relationship, our goal is to identify focal points for therapeutic intervention and more effective markers of early-stage disease.
Our key research questions include:
i) how do homeobox genes control evolution of different types of tumors from the same cell-of-origin?
ii) what sets of homeobox genes regulate tumor progression, and what are their mechanisms?
iii) how do homeobox genes cross-talk with other signaling pathways in tumors?
The studies in my laboratory are multi-disciplinary and integrate cancer biology with developmental biology. The projects include both molecular studies of gene regulation, and studies of tumor growth, histopathology, and interactions with the microenvironment using in vitro and animal models.
|1994||The Australian National University, Canberra, AUS, PHD, Field of study: Medical Sciences|
|1990||The Australian National University, Canberra, AUS, Bachelor Degree of Science with First-Class Honors, Field of study: Biochemistry|
|1999-2000||Research Fellowship, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD|
|1997-1998||Research Fellowship, Unité d'Oncologie Virale, Institut Pasteur, Paris|
|1994-1997||Research Fellowship, Research School of Biological Sciences, The Australian National University, Canberra|
Associate Professor, Department of Molecular and Cellular Oncology, Division of Basic Science Research, University of Texas MD Anderson Cancer Center, Houston, TX, 2013 - 2022
Associate Professor, Department of Systems Biology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, 2007 - 2013
Assistant Professor, Department of Systems Biology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, 2004 - 2007
Faculty member, Graduate School of Biomedical Sciences, University of Texas Health Sciences Center at Houston, Houston, TX, 2002 - Present
Assistant Professor, Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, 2002 - 2003
Research Associate (RFA), Department of Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 2000 - 2002
Institutional Committee Activities
Chair, GSBS Alfred G. Knudson Award Review Committee, 2015 - 2015
Senator (Molecular & Cellular Oncology), Faculty Senate, 2013 - 2016
Member, Executive Committee of the Faculty Senate, 2013 - 2014
Member, Institutional Biosafety Committee, 2013 - 2014
Member, Division of Cancer Medicine Research Awards Committee, 2011 - 2013
Senator (Systems Biology), Faculty Senate, 2010 - 2013
Chair, GSBS Graduate Program in Cancer Biology International Students Admissions Subcommittee, 2009 - 2011
Member, Institutional Research Grants Scientific Review Committee, 2007 - 2010
Member, Institutional Biosafety Committee, 2006 - 2011
Advisory Board Member, HERA Ovarian Cancer Foundation, Carbondale, Colorado, 2002 - 2009
|2003||Eagle Award for Scientific Achievement, Cancer Fighters of Houston|
|2000||Research Fellowship, Prevent Cancer Foundation (formerly Cancer Research Foundation of America)|
|1997||Sidaction Fellowship, Fondation pour la Recherche Medicale, France|
|1990||Australian Postgraduate Research Award, Commonwealth Government of Australia|
|1989||Janet Elspeth Crawford Prize, The Australian National University|
- Ko SY, Lee W, Kenny HA, Dang LH, Ellis LM, Jonasch E, Lengyel E, Naora H. Cancer-derived small extracellular vesicles promote angiogenesis by heparin-bound, bevacizumab-insensitive VEGF, independent of vesicle uptake. Commun Biol 2:386, 2019. PMID: 31646189.
- Lee W, Ko SY, Mohamed MSE, Kenny HA, Lengyel E, Naora H. Neutrophils facilitate ovarian cancer pre-metastatic niche formation in the omentum. J Exp Med 216(1):176-194, 2019. PMID: 30567719.
- Trinh B, Ko SY, Haria D, Barengo N, Naora H. The homeoprotein DLX4 controls inducible nitric oxide synthase-mediated angiogenesis in ovarian cancer. Mol Cancer 14:e97, 2015. PMID: 25924901.
- Haria D, Trinh BQ, Ko SY, Barengo N, Liu J, Naora H. The homeoprotein DLX4 stimulates NF-κB activation and CD44-mediated tumor-mesothelial cell interactions in ovarian cancer. Am J Pathol 185:2298-2308, 2015. PMID: 26067154.
- Trinh BQ, Barengo N, Kim SB, Lee JS, Zweidler-McKay PA,Naora H. The homeobox gene DLX4 regulates erythro-megakaryocytic differentiation by stimulating IL-1β and NF-κB signaling. J Cell Sci 128:3055-3067, 2015. PMID: 26208636.
- Ko SY, Ladanyi A, Lengyel E, Naora H. Expression of the homeobox gene HOXA9 in ovarian cancer induces peritoneal macrophages to acquire an M2 tumor-promoting phenotype. Am J Pathol 184:271-281, 2014. PMID: 24332016.
- Ko SY, Naora H. HOXA9 promotes homotypic and heterotypic cell interactions that facilitate ovarian cancer dissemination via its induction of P-cadherin. Mol Cancer 13:170-178, 2014. PMID: 25023983.
- Usui A, Ko SY, Barengo N, Naora H. P-cadherin promotes ovarian cancer dissemination through tumor cell aggregation and tumor-peritoneum interactions. Mol Cancer Res 12:504-513, 2014. PMID: 24448686.
- Trinh BQ, Ko SY, Barengo N, Lin SY, Naora H. Dual functions of the homeoprotein DLX4 in modulating responsiveness of tumor cells to topoisomerase II-targeting drugs. Cancer Res 73:1000-1010, 2013. PMID: 23222298.
- Ko SY, Barengo N, Ladanyi A, Lee JS, Marini F, Lengyel E, Naora H. HOXA9 promotes ovarian cancer growth by stimulating cancer-associated fibroblasts. J Clin Invest 122:3603-3617, 2012. PMID: 22945634.
- Trinh BQ, Barengo N, Naora H. Homeodomain protein DLX4 counteracts key transcriptional control mechanisms of the TGF-β cytostatic program and blocks the antiproliferative effect of TGF-β. Oncogene 30:2718-2729, 2011. PMID: 21297662.
- Ko SY, Lengyel E, Naora H. The Müllerian HOXA10 gene promotes growth of ovarian surface epithelial cells by stimulating epithelial-stromal interactions. Mol Cell Endocrinol 317:112-119, 2010. PMID: 20036708.
- Zheng J, Chang B, Yang G, Rosen DG, Mills GB, Naora H, Auersperg N, Malpica A, Liu J. Induction of high grade serous carcinoma in human ovarian surface epithelial cells using combined genetic elements and peritoneal microenvironment. Cell Cycle 9:140-145, 2010. PMID: 20016289.
- Ko SY, Guo H, Barengo N, Naora H. Inhibition of ovarian cancer growth by a tumor-targeting peptide that binds eukaryotic translation initiation factor 4E. Clin Cancer Res 15:4336-4347, 2009. PMID: 19458052.
- Hara F, Samuel S, Liu J, Rosen D, Langley RR, Naora H. 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, 2007. PMID: 17456765.
- Yoshida H, Broaddus R, Cheng W, Xie S, Naora H. Deregulation of the HOXA10 homeobox gene in endometrial carcinoma: Role in epithelial-mesenchymal transition. Cancer Res 66:889-897, 2006. PMID: 16424022.
- Cheng W, Liu J, Yoshida H, Rosen D, Naora H. Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract. Nat Med 11:531-537, 2005. PMID: 15821746.
- Yoshida H, Liu J, Samuel S, Cheng W, Rosen D, Naora H. Steroid receptor coactivator-3, a homolog of Taiman that controls cell migration in the Drosophila ovary, regulates migration of human ovarian cancer cells. Mol Cell Endocrinol 245:77-85, 2005. PMID: 16298470.
- Yoshida H, Cheng W, Hung J, Montell D, Geisbrecht E, Rosen D, Liu J, Naora H. Lessons from border cell migration in the Drosophila ovary: A role for myosin VI in dissemination of human ovarian cancer. Proc Natl Acad Sci USA 101:8144-8149, 2004. PMID: 15146066.
- Silver DL, Naora H, Liu J, Cheng W, Montell DJ. Activated signal transducer and activator of transcription (STAT) 3: localization in focal adhesions and function in ovarian cancer cell motility. Cancer Res 64:3550-3558, 2004. PMID: 15150111.
- Naora H, Montz FJ, Chai C-Y, Roden RBS. Aberrant expression of homeobox gene HOXA7 is associated with müllerian-like differentiation of epithelial ovarian tumors and the generation of a specific autologous antibody response. Proc Natl Acad Sci USA 98:15209-15214, 2001. PMID: 11742062.
- Naora H, Yang Y, Montz FJ, Seidman JD, Kurman RJ, Roden RBS. A serologically identified tumor antigen encoded by a homeobox gene promotes growth of ovarian epithelial cells. Proc Natl Acad Sci USA 98:4060-4065, 2001. PMID: 11274429.
- Ko SY, Naora H. Extracellular vesicle membrane-associated proteins: emerging roles in tumor angiogenesis and anti-angiogenesis therapy resistance. Int J Mol Sci 21:5418, 2020. PMID: 32751440.
- Naora H. Heterotypic cellular interactions in the ovarian tumor microenvironment: Biological significance and therapeutic implications. Front Oncol 4:18-24, 2014. PMID: 24567915.
- Ko SY, Naora H. Adaptation of ovarian cancer cells to the peritoneal environment: Multiple mechanisms of the developmental patterning gene HOXA9. Cancer Cell Microenv 1:e379, 2014. PMID: 26000332.
- Ko SY, Naora H. Therapeutic strategies for targeting the ovarian tumor stroma. World J Clin Cases 2:194-200, 2014. PMID: 24945005.
- Haria D, Naora H. Homeobox gene deregulation: Impact on the hallmarks of cancer. Cancer Hallm 1:67-76, 2013. PMID: 24761365.
- Naora H. A peptide-based approach to inhibit the translational machinery in tumors. Chemistry Today 28:26-28, 2010.
- Naora H. The heterogeneity of epithelial ovarian cancers: reconciling old and new paradigms. Expert Rev Mol Med 9:1-12, 2007. PMID: 17477890.
- Naora H. Developmental patterning in the wrong context: The paradox of epithelial ovarian cancers. Cell Cycle 4:86-88, 2005. PMID: 16082202.
- Naora H, Montell DJ. Ovarian cancer metastasis: Integrating insights from disparate model organisms. Nat Rev Cancer 5:355-366, 2005. PMID: 15864277.
- Samuel S, Naora H. Homeobox gene expression in cancer: Insights from developmental regulation and deregulation. Eur J Cancer 41:2428-2437, 2005. PMID: 16199152.
- Naora H. Heterotypic cellular interactions in the ovarian tumor microenvironment. In: Advances in Epithelial Ovarian Cancer: Model Systems, Microenvironmental Influences, Therapy & Origins. Frontiers, 2016.
- Trinh BQ, Naora H. Homeobox genes and their functional significance in ovarian tumorigenesis. In: Ovarian Cancer: Basic Science Perspective. In-Tech Publishing, 2012.
- Hennessy BT, Carey M, Naora H, Mills GB. Ovarian Cancer: Molecular, Cellular and Clinical Biology. In: Ovarian Cancer: State of the Art. Remedica Medical Education & Publishing, 2008.