Department of Reproductive Medicine

Varykina Thackray

Varykina Thackray, PhD
Associate Professor
Division of Reproductive Endocrinology

Telephone: (858) 822-7693
Fax: (858) 534-1438
Email: vthackray@ucsd.edu

Administrative Assistant:
Ruth Montouri (858) 534-1140
rmontouri@ucsd.edu

Visit our site at: The Thackray Lab


Education and Training

Ph.D. in Molecular Biology, 2002
University of Colorado Health Sciences Center

Postdoctoral Fellow, 2002-2008
University of California, San Diego

Honors and Awards

2008 UCSD/UCLA Diabetes and Endocrinology Research Center P&F Award
2008-2011 NIH K01 Mentored Research Scientist Development Award
2009 Women in Endocrinology Young Investigator Award
2011-2016 NIH R01 Research Project Grant
2012 Endocrine Society Early Investigators Award

Professional Activities

Member, Endocrine Society
  Ad hoc Reviewer, ENDO Abstracts 2012
  Research Affairs Core Committee 2013-2016
  Endocrinology Editorial Board 2013-2016
Member, Society for the Study of Reproduction
Member, Women in Endocrinology
  Program Committee, 2007-2009
  Communications Committee 2009-2013
Member, Association for Women in Science
  Scholarship Committee, 2006-present (Co-Chair 2006-2008)
Member, Doris A. Howell Foundation for Women’s Health Research Advisory Council
Ad hoc Reviewer, NIH/CSR ICER and NIH/CSR AREA in EMNR Study Section 2012-2014
Ad hoc Reviewer, Andrology, Endocrinology, Environmental Health, Genesis, Journal of Biological Chemistry, Molecular and Cellular Endocrinology, Molecular Endocrinology and PLoS One

Teaching

Hormone Action (BIOM 226); Foundations of Human Biology Small Literature Group; Clinical Foundations Problem Based Learning Group

Service

2008-present Member, UCSD Center for Reproductive Science and Medicine
2008-present Member, UCSD/UCLA Diabetes and Endocrinology Research Center (DERC)
2009-present Member, UCSD Reproduction Journal Club Steering Committee
2011-present Faculty Mentor, NIH Postdoctoral Training Program in Reproductive Sciences
2011-present Faculty Mentor, UCSD Biological Sciences Integrated BS/MS Program and Individual Research for Undergraduates (BISP 199)

2012-present Faculty Mentor, UCSD Institutional Research and Academic Career Development Post-doctoral Training Program (IRACDA)

 

Research Interests

Metabolic disorders, including anorexia and obesity in the U.S. are reaching epidemic proportions with far-reaching societal and economic consequences. Women with metabolic disorders often have reproductive disorders including early onset of puberty, menstrual irregularities, pregnancy complications, and infertility. One of the main objectives of our research is to comprehend the mechanisms controlling gonadotropin gene expression and understand how production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is altered under specific pathophysiological conditions.

Currently, a major focus of our research is to investigate the role of forkhead transcription factors in pituitary gonadotrope cells. Members of the FOXO family are regulated by insulin signaling pathways and thus, may prove to be a key regulatory link between metabolism and reproduction. FOXOs represent the mammalian orthologs of DAF-16, which regulates longevity, metabolism and fertility in the nematode, C. elegans. FOXOs regulate diverse cellular functions such as apoptosis, stress resistance and metabolism but their role in the pituitary has not been explored. Our preliminary data demonstrates that FOXO1 is expressed and is regulated by insulin signaling in pituitary gonadotropes. We have also shown that FOXO1 can suppress LH and FSH synthesis. We are currently studying how FOXOs regulate gonadotropin production using in vitro biochemical assays, tissue culture cell model systems and conditional knockout mice.

Another project in the lab focuses on a G/T single nucleotide polymorphism (SNP) at 211 relative to the transcription start site of the human FSHB promoter which is associated with reduced serum FSH levels in men. While the SNP resides in a putative hormone response element, we recently reported that, unlike the mouse gene, human FSHB was not induced by androgens or progestins in gonadotrope cells. On the other hand, we found that the LHX3 homeodomain transcription factor binds to an 11 bp element in the human FSHB promoter which includes the -211 nucleotide. We also demonstrated that LHX3 bound with greater affinity to the wild-type human FSHB promoter compared to the 211 G/T mutation and that FSHB transcription was decreased in gonadotrope cells with the 211 G/T mutation compared to the wild-type FSHB promoter. We are currently studying how LHX3 binding to the human promoter regulates FSH production especially with regards to the -211 G/T SNP.

 

Selected Publications

Spady, T., Shayya, R., Thackray, V., Ehrensberger, L., Bailey, J., and Mellon, P. (2004) Androgen Regulates FSHβ Gene Expression in an Activin-Dependent Manner in Immortalized Gonadotropes. Molecular Endocrinology 18(4): 925-940

Coss, D., Thackray, V. and Mellon, P. (2005) Activin Regulates Luteinizing Hormone β-Subunit Gene Expression through Smad-Binding and Homeobox Elements. Molecular Endocrinology 19(10): 2610-23

Thackray, V., McGillivray, S. and Mellon, P. (2006) Androgens, Progestins and Glucocorticoids Induce Follicle-Stimulating Hormone β-Subunit Gene Expression at the Level of the Gonadotrope. Molecular Endocrinology 20(9): 2062-79

McGillivray, S., Thackray, V. and Mellon, P. (2007) Activin and Glucocorticoids Synergistically Activate Follicle-Stimulating Hormone β-Subunit Gene Expression in the Immortalized LβT2 Gonadotrope Cell-Line. Endocrinology 148(2): 762-773

Thackray, V. and Mellon, P. (2008) Synergistic Induction of Follicle-Stimulating Hormone β-Subunit Gene Expression by Gonadal Steroid Hormone Receptors and Smads. Endocrinology 149(3): 1091-102

Sasson, R., Luu, S., Thackray V., and Mellon, P. (2008) Glucocorticoids Induce Human Glycoprotein Hormone Alpha-Subunit Gene Expression in the Gonadotrope. Endocrinology 149(7): 3643-3655

Thackray, V., Hunnicutt. J., Memon, A., Ghochani, Y., and Mellon, P. (2009) Progesterone Suppresses Basal Expression and GnRH Induction of the Luteinizing Hormone β-Subunit Gene. Endocrinology 150(5): 2395-2403

Thackray, V., Mellon, P. and Coss, D. (2010) Hormones in Synergy: Regulation of the Pituitary Gonadotropin Genes. Molecular and Cellular Endocrinology 314(2):192-203

Breen, K., Thackray, V., Coss, D., and Mellon, P. (2010) Runt-Related Transcription Factors Impair Activin Induction of the Follicle-Stimulating Hormone β-Subunit Gene. Endocrinology 151(6):2669-80

Coss, D., Mellon, P. and Thackray, V. (2010) A FoxL in the Smad House: Activin Regulation of FSH. Trends in Endocrinology and Metabolism 21(9):562-568

Ghochani, Y., Saini, J., Mellon, P., and Thackray, V. (2012) FoxL2 Is Involved in the Synergy Between Activin and Progestins on the Follicle-Stimulating Hormone β-Subunit Promoter. Endocrinology 153(4):2023-2033

Breen, K., Thackray, V., Hsu, T., Mak-McCully, R., Coss, D., and Mellon, P. (2012) Stress Levels of Glucocorticoids Inhibit LHβ-Subunit Gene Expression in Gonadotrope Cells. Molecular Endocrinology 26(10):1716–1731

 

Arriola, D., Mayo, S., Skarra, D., Benson, C., and Thackray, V. (2012) FOXO1 Transcription Factor Inhibits Luteinizing Hormone β Gene Expression in Pituitary Gonadotrope Cells. Journal of Biological Chemistry 28;287(40):33424-35

 

Benson, C.A., Kurz, T.L. and Thackray, V.G. (2013) A Human FSHB Promoter SNP Associated with Low FSH Levels in Men Impairs LHX3 Binding and FSHB Transcription. Endocrinology 154(9):3016–3021

 

Skarra, D.V., Arriola, D.J., Benson, C.A., and Thackray, V.G. (2013) Forkhead Box O1 Is a Repressor of Basal and GnRH-Induced Fshb Transcription in Gonadotropes. Molecular Endocrinology 27(11):1825–1839

 

Thackray, V.G. (2014) Fox Tales: Regulation of Gonadotropin Gene Expression by Forkhead Transcription Factors. Molecular and Cellular Endocrinology 385(1-2):62-70

 
 
 
 
 
 

 
 

Faculty