Hugh S. Taylor MD
Anita O'Keeffe Young Professor of Obstetrics, Gynecology, and Reproductive Sciences and Professor of Molecular, Cellular, and Developmental Biology; Chief of Obstetrics and Gynecology, Yale-New Haven Hospital; Anita O'Keeffe Young Professor of Women's Health, Yale University
Research Interests
Homeobox genes; Embryo implantation; Endometriosis; Stem cells; Menopause; uterine Development; Endocrine disruption; Developmental programming
Research Summary
Homeodomain proteins are essential to normal development and differentiation in Drosophila and humans. They act as transcriptional regulatory proteins. How they impart their specificity of action is still poorly understood. This study is designed to characterize the molecular specificity of homeodomain protein action. Phase I will characterize the DNA sequences that impart specificity of homeodomain binding.
The model system used will be the Abdominal-Bhomeoprotein response element of the Drosophila empty spiracles gene. This newly identified element will be sequenced and then functionally important regions will be identified by an evolutionary, and mutational approach and tested for function in a transgenic fly strain. The specific Abdominal-B homeoprotein binding sites will be compared to another homeobox response element. Attempts will be made to change sequences in one response element to make it specific for another homeobox protein; thus those sequences essential for specificity of action will be determined. The principles of homeotic specificity learned will be tested for applicability to humans using homologus human homeobox genes in a transgenic fly strain.
Phase II will attempt to identify and characterize novel co-factors that are likely involved in refining homeotic specificity. Once identified, these co-factors will be assayed for conservation in humans. These genes and co-factors will then be assayed for function in mammals. A comprehensive characterization of the determinants of homeotic specificity will be delineated in both Drosophila and humans.
Selected Publications
- Cakmak H and Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Human Reproduction Update 2011, 17(2):242-253.
- Wolff EP, Gao XB, Yao K, Du H, Elsworth JB and Taylor HS. Endometrial stem cell transplantation restores dopamine production in a Parkinson's Disease model. Journal of Cellular and Molecular Medicine 2011, 15(4):747-755.
- Santamaria-Costa X, Massasa E, Feng Y, Wolff E and Taylor HS. Differentiation of human endometrial stromal stem cells into insulin producing cells for treatment of murine diabetes. Molecular Therapy 2011, 19 (11), 2065–2071.
- Bromer JG, Zhou Y, Taylor MB, Doherty L, and Taylor HS. Bisphenol A (BPA) exposure in utero leads to epigenetic alterations in the development programming of uterine estrogen response. Journal of the Federation of American Societies for Experimental Biology 2010, 24(7):2273-2280.
- Andyikan V, Taylor HS. Gynecologic tumor histologic type is regulated by WT1 repression of Hox gene expression. Journal of Cellular and Molecular Medicine 2009, 13(11-12):4532-4539.
- Bromer JG, Wu J, Zhou V and Taylor HS. Hypermethylation of HOXA10 by in utero diethylstilbestrol exposure: an epigenetic mechanism for altered developmental programming. Endocrinology 2009, 150(7):3376-3382.
- Lee B, Du H and Taylor HS. Experimental endometriosis induces DNA methylation and altered gene expression in eutopic endometrium. Biology of Reproduction 2009, 80(1):79-85.
- Connell KA, Guess MK, Chen H, Andykan V, Bercik R, and Taylor HS. HOXA11 is critical for development and maintenance of uterosacral ligaments and deficient in pelvic prolapse. Journal of Clinical Investigation 2008, 118(3):1050-1055.
- Smith C and Taylor HS. Xenoestrogen exposure imprints expression of genes (HOXA10) required for normal uterine developmental. Journal of the Federation of American Societies for Experimental Biology 2007, 21 (1): 239-246.
- Martin R, Akbas GE and Taylor HS. Differential cell specific modulation of HOXA10 by estrogen and SP1 response elements. J Clin Endocrinol Metab 2007, 92(5):1920-1926.
Selected Publications
- Cakmak H and Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Human Reproduction Update 2011, 17(2):242-253.
- Wolff EP, Gao XB, Yao K, Du H, Elsworth JB and Taylor HS. Endometrial stem cell transplantation restores dopamine production in a Parkinson's Disease model. Journal of Cellular and Molecular Medicine 2011, 15(4):747-755.
- Santamaria-Costa X, Massasa E, Feng Y, Wolff E and Taylor HS. Differentiation of human endometrial stromal stem cells into insulin producing cells for treatment of murine diabetes. Molecular Therapy 2011, 19 (11), 2065–2071.
- Bromer JG, Zhou Y, Taylor MB, Doherty L, and Taylor HS. Bisphenol A (BPA) exposure in utero leads to epigenetic alterations in the development programming of uterine estrogen response. Journal of the Federation of American Societies for Experimental Biology 2010, 24(7):2273-2280.
- Andyikan V, Taylor HS. Gynecologic tumor histologic type is regulated by WT1 repression of Hox gene expression. Journal of Cellular and Molecular Medicine 2009, 13(11-12):4532-4539.
- Bromer JG, Wu J, Zhou V and Taylor HS. Hypermethylation of HOXA10 by in utero diethylstilbestrol exposure: an epigenetic mechanism for altered developmental programming. Endocrinology 2009, 150(7):3376-3382.
- Lee B, Du H and Taylor HS. Experimental endometriosis induces DNA methylation and altered gene expression in eutopic endometrium. Biology of Reproduction 2009, 80(1):79-85.
- Connell KA, Guess MK, Chen H, Andykan V, Bercik R, and Taylor HS. HOXA11 is critical for development and maintenance of uterosacral ligaments and deficient in pelvic prolapse. Journal of Clinical Investigation 2008, 118(3):1050-1055.
- Smith C and Taylor HS. Xenoestrogen exposure imprints expression of genes (HOXA10) required for normal uterine developmental. Journal of the Federation of American Societies for Experimental Biology 2007, 21 (1): 239-246.
- Martin R, Akbas GE and Taylor HS. Differential cell specific modulation of HOXA10 by estrogen and SP1 response elements. J Clin Endocrinol Metab 2007, 92(5):1920-1926.
- Du H and Taylor HS. Contribution of Bone marrow Derived Cells to Endometrium and Endometriosis. Stem Cells 2007, 25(8):2082-2086.
- Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. Journal of the American Medical Association 2004, 292(1):81-5.
- Block K, Kardana A, Igarashi P and Taylor HS. In Utero Diethylstilbestrol (DES), Exposure Alters Hox Gene Expression in the Developing Müllerian System. Journal of the Federation of American Societies for Experimental Biology 2000, 14(7):1101-1108.
- Taylor HS, Igarashi P, Olive DL, Arici A. Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium., Journal of Clinical Endocrinology and Metabolism 1999, 84(3):1129-35.
- Arici A, Seli E, Senturk LM, Gutierrez LS, Oral E, Taylor HS. Interleukin-8 in the human endometrium. Journal of Clinical Endocrinology and Metabolism 1998, 83(5):1783-7.
- Taylor HS, Arici A, Olive D, Igarashi P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. Journal of Clinical Investigation 1998, 101(7):1379-84.
- Taylor HS. A regulatory element of the empty spiracles homeobox gene is composed of three distinct conserved regions that bind regulatory proteins., Molecular Reproduction and Development 1998, 49(3):246-53.
- Taylor HS, Vanden Heuvel GB, Igarashi P. A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes. Biology of Reproduction 1997, 57(6):1338-45.
