Hugh Taylor, MD
Research & Publications
Biography
News
Extensive Research Description
Endometriosis is characterized by the ectopic growth of endometrium outside of the uterus. It is a common and debilitating disease, causing pain or infertility in approximately 10% of reproductive age women. We have identified several novel mechanisms that lead to and regulate this disease. Our group has demonstrated a role for stem cells, epigenetics and micro RNA in this disease. We have also identified several novel markers of endometriosis and therapies to treat the disease.
Endometrial renewal in each menstrual cycle depends on a small pool of tissue-specific stem cells. These endogenous stem cells allow the rapid regeneration of the endometrium necessary to support pregnancy. My laboratory continues to explore the role of adult stem cells from the endometrium and their role in pathophysiology. We were the first to identify an exogenous source of stem cells that contribute to endometrial regeneration. Bone marrow and other tissues contribute stem cells to the circulation that can engraft and repair the uterus; these cells have proven to be useful in the treatment of Asherman’s syndrome in an animal model. Further, some of these cells remain as multipotent stem cells in the uterine endometrium and can be readily obtained in a simple office biopsy. The cells display remarkable plasticity and we have been able to differentiate them into insulin producing cells, neuronal cells, cartilage as well as other cell types. We have used these differentiated cells in regenerative medicine and have demonstrated their effectiveness in animal models of diseases including diabetes and Parkinson’s disease.
The laboratory also studies uterine development. We were the first to describe the molecular mechanism by which the Mullerian duct differentiates into different components of the adult female reproductive track. Differential expression of HOX genes directs segments of the Mullerian duct to take on distinct developmental identities, resulting in the axial differentiation of the fallopian tubes, uterus, cervix and vagina. Perturbation of this process leads to uterine developmental anomalies and infertility. We have examined the role of endocrine disruptors such as bisphenol A (BPA) and diethylstilbestrol (DES) on the developing female reproductive system. These agents and other environmental estrogens disturb the axial patterning of the female reproductive tract altering development and adult reproductive performance. We have demonstrated that this is largely accomplished by epigenetic reprogramming driven by these compounds.
Many of the same genes that are used in uterine development are subsequently used in cyclic endometrial development in adults. We have characterized the role of HOXA10 in endometrial development and receptivity to embryo implantation. This gene is required for fertility and abnormally expressed in several forms of infertility, leading to failed implantation and pregnancy loss.
We also conduct clinical and translational work on the menopause. We have a particular interest in the effects of menopausal hormone therapies on the endometrium.
Reproductive endocrinology; Discovery to cure
Coauthors
Research Interests
Endometriosis
Selected Publications
- HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium.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. The Journal Of Clinical Investigation 1998, 101:1379-84.
- HOX gene expression is altered in the endometrium of women with endometriosis.Taylor HS, Bagot C, Kardana A, Olive D, Arici A. HOX gene expression is altered in the endometrium of women with endometriosis. Human Reproduction (Oxford, England) 1999, 14:1328-31.
- Transcriptional repression of peri-implantation EMX2 expression in mammalian reproduction by HOXA10.Troy PJ, Daftary GS, Bagot CN, Taylor HS. Transcriptional repression of peri-implantation EMX2 expression in mammalian reproduction by HOXA10. Molecular And Cellular Biology 2003, 23:1-13.
- Hypermethylation of homeobox A10 by in utero diethylstilbestrol exposure: an epigenetic mechanism for altered developmental programming.Bromer JG, Wu J, Zhou Y, Taylor HS. Hypermethylation of homeobox A10 by in utero diethylstilbestrol exposure: an epigenetic mechanism for altered developmental programming. Endocrinology 2009, 150:3376-82.
- Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response.Bromer JG, Zhou Y, Taylor MB, Doherty L, Taylor HS. Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response. FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2010, 24:2273-80.
- Maternal ghrelin deficiency compromises reproduction in female progeny through altered uterine developmental programming.Martin JR, Lieber SB, McGrath J, Shanabrough M, Horvath TL, Taylor HS. Maternal ghrelin deficiency compromises reproduction in female progeny through altered uterine developmental programming. Endocrinology 2011, 152:2060-6.
- A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis.Grechukhina O, Petracco R, Popkhadze S, Massasa E, Paranjape T, Chan E, Flores I, Weidhaas JB, Taylor HS. A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis. EMBO Molecular Medicine 2012, 4:206-17.
- Treatment with bazedoxifene, a selective estrogen receptor modulator, causes regression of endometriosis in a mouse model.Kulak J, Fischer C, Komm B, Taylor HS. Treatment with bazedoxifene, a selective estrogen receptor modulator, causes regression of endometriosis in a mouse model. Endocrinology 2011, 152:3226-32.
- Cigarette smoke inhibits recruitment of bone-marrow-derived stem cells to the uterus.Zhou Y, Gan Y, Taylor HS. Cigarette smoke inhibits recruitment of bone-marrow-derived stem cells to the uterus. Reproductive Toxicology (Elmsford, N.Y.) 2011, 31:123-7.
- Demonstration of multipotent stem cells in the adult human endometrium by in vitro chondrogenesis.Wolff EF, Wolff AB, Hongling Du, Taylor HS. Demonstration of multipotent stem cells in the adult human endometrium by in vitro chondrogenesis. Reproductive Sciences (Thousand Oaks, Calif.) 2007, 14:524-33.
- Contribution of bone marrow-derived stem cells to endometrium and endometriosis.Du H, Taylor HS. Contribution of bone marrow-derived stem cells to endometrium and endometriosis. Stem Cells (Dayton, Ohio) 2007, 25:2082-6.
- Implantation failure: molecular mechanisms and clinical treatment.Cakmak H, Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Human Reproduction Update 2011, 17:242-53.
- Endometrial stem cell transplantation restores dopamine production in a Parkinson's disease model.Wolff EF, Gao XB, Yao KV, Andrews ZB, Du H, Elsworth JD, Taylor HS. Endometrial stem cell transplantation restores dopamine production in a Parkinson's disease model. Journal Of Cellular And Molecular Medicine 2011, 15:747-55.
- Derivation of insulin producing cells from human endometrial stromal stem cells and use in the treatment of murine diabetes.Santamaria X, Massasa EE, Feng Y, Wolff E, Taylor HS. Derivation of insulin producing cells from human endometrial stromal stem cells and use in the treatment of murine diabetes. Molecular Therapy : The Journal Of The American Society Of Gene Therapy 2011, 19:2065-71.
- WT1 represses HOX gene expression in the regulation of gynaecologic tumour histologic type.Andikyan V, Taylor HS. WT1 represses HOX gene expression in the regulation of gynaecologic tumour histologic type. Journal Of Cellular And Molecular Medicine 2009, 13:4522-31.
- Experimental murine endometriosis induces DNA methylation and altered gene expression in eutopic endometrium.Lee B, Du H, Taylor HS. Experimental murine endometriosis induces DNA methylation and altered gene expression in eutopic endometrium. Biology Of Reproduction 2009, 80:79-85.
- HOXA11 is critical for development and maintenance of uterosacral ligaments and deficient in pelvic prolapse.Connell KA, Guess MK, Chen H, Andikyan V, Bercik R, Taylor HS. HOXA11 is critical for development and maintenance of uterosacral ligaments and deficient in pelvic prolapse. The Journal Of Clinical Investigation 2008, 118:1050-5.
- Xenoestrogen exposure imprints expression of genes (Hoxa10) required for normal uterine development.Smith CC, Taylor HS. Xenoestrogen exposure imprints expression of genes (Hoxa10) required for normal uterine development. FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2007, 21:239-46.
- Differential cell-specific modulation of HOXA10 by estrogen and specificity protein 1 response elements.Martin R, Taylor MB, Krikun G, Lockwood C, Akbas GE, Taylor HS. Differential cell-specific modulation of HOXA10 by estrogen and specificity protein 1 response elements. The Journal Of Clinical Endocrinology And Metabolism 2007, 92:1920-6.
- Endometrial cells derived from donor stem cells in bone marrow transplant recipients.Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA 2004, 292:81-5.
- In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing müllerian system.Block K, Kardana A, Igarashi P, Taylor HS. In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing müllerian system. FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology 2000, 14:1101-8.
- Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium.Taylor HS, Igarashi P, Olive DL, Arici A. Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. The Journal Of Clinical Endocrinology And Metabolism 1999, 84:1129-35.
- Interleukin-8 in the human endometrium.Arici A, Seli E, Senturk LM, Gutierrez LS, Oral E, Taylor HS. Interleukin-8 in the human endometrium. The Journal Of Clinical Endocrinology And Metabolism 1998, 83:1783-7.
- A regulatory element of the empty spiracles homeobox gene is composed of three distinct conserved regions that bind regulatory proteins.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, 49:246-53.
- A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes.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, 57:1338-45.
- Novel therapies targeting endometriosis.Taylor HS, Osteen KG, Bruner-Tran KL, Lockwood CJ, Krikun G, Sokalska A, Duleba AJ. Novel therapies targeting endometriosis. Reproductive Sciences (Thousand Oaks, Calif.) 2011, 18:814-23.
- Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause: Ancillary Study of the Kronos Early Estrogen Prevention Study (KEEPS).Taylor HS, Tal A, Pal L, Li F, Black DM, Brinton EA, Budoff MJ, Cedars MI, Du W, Hodis HN, Lobo RA, Manson JE, Merriam GR, Miller VM, Naftolin F, Neal-Perry G, Santoro NF, Harman SM. Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause: Ancillary Study of the Kronos Early Estrogen Prevention Study (KEEPS). JAMA Internal Medicine 2017, 177:1471-1479.
- Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist.Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, Diamond MP, Surrey E, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, Rowan JP, Duan WR, Ng J, Schwefel B, Thomas JW, Jain RI, Chwalisz K. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. The New England Journal Of Medicine 2017, 377:28-40.
Clinical Trials
| Conditions | Study Title |
|---|---|
| Other Endocrine System; Other Female Genital | Endometrium and Metabolism |
| Women's Health | Assess Safety and Efficacy of Vilaprisan in Subjects With Uterine Fibroids (ASTEROID 6) |