Physiology and Pharmacology

Edwin R. Sanchez


Professor

Telephone: (419) 383-4182, 383-4187
FAX: (419) 383-2871

e-mail: Edwin.Sanchez@utoledo.edu

For more information on Steroid Receptor Research, see: 
Steroid Receptor Associated Proteins Resource
or Glucocorticoid Receptor Resource 

Training

  • B.A., Biology, 1974, Wesleyan University
  • Ph.D., Human Genetics, 1983, University of Michigan

Appointments

  • Postdoctoral Fellow, Department of Human Genetics, University of Michigan, 1983-1984
  • Research Fellow, Department of Pharmacology, University of Michigan, 1984- 1987
  • Research Investigator, Department of Pharmacology, University of Michigan, 1987-1989
  • Assistant Research Scientist, Department of Pharmacology, University of Michigan, 1989
  • Assistant Professor of Pharmacology and Therapeutics, Medical College of Ohio, 1989-1994
  • Associate Professor of Pharmacology and Therapeutics, Medical College of Ohio, 1994-2000
  • Professor of Physiology, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Health Science Campus, 2000-present
  • Assistant Director, Center for Diabetes and Endocrine Research (CeDER), University of Toledo College of Medicine, Health Science Campus, 2006-
Research Interests:

Control of steroid receptor physiology by molecular chaperones

Dr. Sanchez’s research focuses on the steroid hormone receptors, with an emphasis on the tetratricopeptide repeat (TPR) proteins that act as molecular chaperones to the receptors. These chaperone proteins include: FK506-binding protein 52 (FKBP52), FKBP51, protein phosphatase 5 (PP5) and cyclophilin 40 (Cyp40).

Steroid hormones are a large class of cholesterol-derived molecules, which serve to control the functional states of a variety of cells and target tissues. These hormones include progestins, estrogens, androgens, mineralocorticoids and glucocorticoids. Many important endocrine and physiological processes are controlled by these hormones, including immunity and inflammation, glucose and fatty acid metabolism, male and female reproduction, and blood pressure. The central thrust of the research program is to understand how the TPR chaperones described above contribute to the actions of steroid receptors at the molecular, cellular and physiological level

The most recent findings at the Sanchez laboratory suggest that the TPR chaperones act as tissue-selective modulators of steroid receptor physiology. FKBP52 was found to exert a stimulatory effect on progesterone receptor action only in the uterus and not in other female reproductive organs. Similarly, FKBP52 is needed for the androgen receptor contribution to embryonic development of select male reproductive organs, such as the prostate gland, but not others. Both FKBP51 and Cyp40 were found to be critically important to androgen receptor action in the adult prostate gland, and may be key factors necessary for the onset and progression of prostate cancer. Most recently, the laboratory has uncovered an interesting and unique reciprocal relationship between FKBP52 and FKBP51 on the activity of glucocorticoid receptors in liver, muscle and adipose tissues. Reciprocal modulation of the glucocorticoid receptor is such that these two chaperones serve to either increase or decrease the involvement of glucocorticoid receptors in development of metabolic syndrome and propensity to type 2 diabetes. Lastly, the laboratory has discovered a novel isoform of the glucocorticoid receptor (GRβ) in the mouse and its potential role in insulin action.

Taken as a whole, this investigative effort has identified TPR proteins as novel and potentially important targets for drug development against male and female infertility, prostate cancer, and metabolic disorders, such as diabetes and obesity.

Dr. Sanchez has authored 80 research and review articles. His research has been continuously funded by grants from the NIH.


Representative Publications

Sánchez E.R. (1990): Hsp56: a novel heat shock protein associated with untransformed steroid-receptor complexes. J. Biol. Chem. 265:22067-22070.

Sánchez E.R. (1992): Heat shock induces translocation to the nucleus of the unliganded glucocorticoid receptor. J. Biol. Chem. 267: 17-20.

Ning Y.-M. and Sánchez E.R. (1993): Potentiation of glucocorticoid receptor-mediated gene expression by the immunophilin ligands FK506 and rapamycin. J. Biol. Chem. 268: 6073-6076.

Sánchez E.R., Hu J.-L., Zhong S., Shen, P., Greene, M.J. and Housley P.R. (1994): Potentiation of glucocorticoid receptor-mediated gene expression by heat and chemical shock. Mol. Endocrinol. 8: 408-421.

Ning Y.-M. and Sánchez E.R. (1995): Stabilization in vitro of the untransformed glucocorticoid receptor complex of S49 lymphocytes by the immunophilin ligand FK506. J. Steroid Biochem. Mol. Biol. 52: 187-194.

Ning Y.-M. and Sánchez E.R. (1995): Evidence for a functional interaction between calmodulin and the glucocorticoid receptor. Biochem. Biophys. Res. Commun. 208: 48-54.

Renoir J.M., Mercier-Bodard C., Hoffman K., Le Bihan S., Ning Y.-M., Sánchez E.R., Handschumacher E. and Baulieu E.-E. (1995): Cyclosporin A, like FK506, potentiates dexamethasone-induced MMTV-CAT activity in LMCAT cells: A possible role for different heat shock protein-binding immunophilins (HBIs) in glucocorticoid receptor-mediated gene expression. Proc. Natl. Acad. Sci. 92:4977-4981.

Ning Y.-M. and Sánchez E.R. (1996): In vivo evidence for the generation of a glucocorticoid receptor-hsp90 complex incapable of binding hormone by the calmodulin antagonist phenoxybenzamine. Mol. Endocrinol. 10:14-23.

Hu, J.-L., Guan, X.-J., and Sánchez, E.R. (1996): Enhancement of glucocorticoid receptor-mediated gene expression by cellular stress: evidence for the involvement of a heat shock-initiated factor or process during recovery from stress. Cell Stress & Chaperones 1:197-205.

Martinez, E., Moore, D.D., Keller, E., Pearce, D., Robinson, V., MacDonald, P.N., Simons, S.S., Sánchez, E.R., and Danielsen, M. (1997): The nuclear receptor resource project. Nucleic Acids Research 25:163-165.

Martinez, E., Moore, D.D., Keller, E., Pearce, D., Vanden Heuvel, J.P., Robinson, V., Gottlieb, B., MacDonald, P.N., Simons, S.S., Sánchez, E.R., and Danielsen, M. (1998): The nuclear receptor resource: A growing family. Nucleic Acids Research 26:239-241.

Li, D., Li Calzi, S., and Sánchez, E.R. (1999): Inhibition of heat shock factor activity prevents heat shock potentiation of glucocorticoid receptor-mediated gene expression. Cell Stress & Chaperones 4:223-234.

Li, D.P., Periyasamy, S., Jones, T.J., and Sanchez, E.R. (2000): Heat and chemical shock potentiation of glucocorticoid receptor transactivation requires Heat Shock Factor (HSF) activity. modulation of HSF by vanadate and wortmannin. J. Biol. Chem. 275: 26058-26065.

Morishima, Y., Murphy, P.J., Li, D.P., Sanchez, E.R., and Pratt, W.B. (2000): Stepwise assembly of glucocorticoid receptor.hsp90 heterocomplex resolves two sequential ATP-dependant events involving first hsp70 and then hsp90 in opening of the steroid binding pocket. J. Biol. Chem. 275: 18054-18060.

Wadekar, S., Li, D., Periyasamy, S., and Sanchez, E.R. (2001) Inhibition of heat shock transcription factor by glucocorticoid receptor. Mol. Endocrinol. 15:1396-1410.

Li Calzi, S., Periyasamy, S., Li, D., and Sanchez, E.R. (2002) Vanadate increases glucocorticoid receptor-mediated gene expression: a novel mechanism for potentiation of a steroid receptor. J. Steroid Biochem. Mol. Biol. 80:35-47.

Davies, T.H., Ning, Y-M., and Sanchez, E.R. (2002) A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins. J. Biol. Chem. 277:4597-4600.

Periyasamy, S. and Sanchez, E.R. (2002) Antagonism of glucocorticoid receptor transactivity and cell growth inhibition by transforming growth factor-ß through AP-1-mediated transcriptional repression. Int. J. Biochem. Cell Biol. 34:1571-1585.

Wadekar, S., Li, D., and Sanchez, E.R. (2004) Agonist-activated glucocorticoid receptor inhibits binding of heat shock factor 1 to the Hsp70 promoter in vivo. Mol. Endocrinol. 18:500-508.

Periyasamy, S., Warrier, M., Tillekeratne, M.P., Shou, W., and Sanchez, E.R. (2007) The immunophilin ligands cyclosporin A and FK506 suppress prostate cancer cell growth by androgen receptor-dependent and -independent mechanisms. Endocrinology. 148(10):4716-4726.

Jones, T., Li, D., Wolf, I.M., Wadekar, S., Periyasamy, S., and Sanchez, E.R. (2004) Enhancement of glucocorticoid receptor-mediated gene expression by constitutively-active heat shock factor 1. Mol. Endocrinol. 18:509-520.

Davies, T. and Sanchez, E.R. (2005) FKBP52: An FK506-binding tetratricopeptide repeat protein. "Molecules in Focus". Int. J. Biochem. Cell. Biol. 37:42-47.

Davies, T.H., Ning, Y.M., and Sanchez, E.R. (2005) Differential control of glucocorticoid receptor hormone-binding function by tetratricopeptide repeat (TPR) proteins and the immunosuppressive ligand FK506. Biochemistry 15:2030-2038.

Li, D. and Sanchez, E.R. (2005) Glucocorticoid receptor and heat shock factor 1: novel mechanism of reciprocal regulation. Vitam. Horm. 71:239-262.

Yang, Z., Wolf, I.M., Chen, H., Periyasamy, S., Chen, Z., Yong, W., Shi, S., Zhao, W., Xu, J., Srivastava, A., Sanchez, E.R., and Shou, W. (2006) FKBP52 is essential to uterine reproductive physiology controlled by the progesterone receptor A isoform. Mol Endocrinol. (11):2682-2694.

Yong, W., Yang, Z., Periyasamy, S., Chen, H., Yucel, S., Li, W., Lin, L.Y., Wolf, I.M., Cohn, M.J., Baskin, L.S., Sanchez, E.R., and Shou, W. (2007) Essential role for Co-chaperone Fkbp52 but not Fkbp51 in androgen receptor-mediated signaling and physiology. J. Biol. Chem. 282(7):5026-5036.

Periyasamy, S., Warrier, M., Tillekeratne, M.P., Shou, W., and Sanchez, E.R. (2007) The immunophilin ligands cyclosporin A and FK506 suppress prostate cancer cell growth by androgen receptor-dependent and -independent mechanisms. Endocrinology. 148(10):4716-4726.

Yong, W., Bao, S., Chen, H., Li, D., Sanchez, E.R., and Shou, W. (2007) Mice lacking protein phosphatase 5 are defective in ataxia telangiectasia mutated (ATM)-mediated cell cycle arrest. J Biol Chem. May 18;282(20):14690-14694.

Hinds, T.D., Jr. and Sanchez, E.R. (2007) Protein phosphatase 5. Int J Biochem Cell Biol. 2007 Aug 30.

Heitzer, M.D., Wolf, I.M., Sanchez, E.R., Witchel, S.F., and DeFranco, D.B. (2007) Glucocorticoid receptor physiology. Rev Endocr Metab Disord. Dec;8(4):321-330.

Banerjee, A., Periyasamy, S., Wolf, I.M., Hinds, T.D., Jr, Yong, W., Shou, W. and Sanchez, E. (2008) Control of glucocorticoid and progesterone receptor subcellular localization by the ligand-binding domain is mediated by distinct interactions with tetratricopeptide repeat proteins. Biochemistry Sep 30; 47(39):10471-80. Epub 2008 Sep 5

Wolf, I.M., Periyasamy, S., Hinds, T. Jr., Yong, W., Shou, W., and Sanchez, E.R. (2008) Targeted ablation reveals a novel role of FKBP52 in gene-specific regulation of glucocorticoid receptor transcriptional activity. J. Steroid Biochem Mol Biol glucocorticoid receptor transcriptional activity. J Steroid Biochem Mol Biol 113

Warrier, M., Hinds, T. D. J., Ledford, K. J., Cash, H. A., Patel, P. R., Bowman, T. A., Stechschulte, L. A., Yong, W., Shou, W., Najjar, S. M. & Sanchez, E. R. Susceptibility to diet-induced hepatic steatosis and glucocorticoid resistance in FK506-binding protein 52-deficient mice. Endocrinology 151, 3225-3236 (2010). PMC2903936

Periyasamy, S., Hinds, T. J., Shemshedini, L., Shou, W. & Sanchez, E. R. FKBP51 and Cyp40 are positive regulators of androgen-dependent prostate cancer cell growth and the targets of FK506 and cyclosporin A. Oncogene 29, 1691-1701 (2010). PMC3040472

Hinds, T. D. J., Ramakrishnan, S., Cash, H. A., Stechschulte, L. A., Heinrich, G., Najjar, S. M. & Sanchez, E. R. Discovery of glucocorticoid receptor-beta in mice with a role in metabolism. Mol Endocrinol 24, 1715-1727 (2010). PMC2940475

Chen, H., Yong, W., Hinds, T. D. J., Yang, Z., Zhou, Y., Sanchez, E. R. & Shou, W. Fkbp52 regulates androgen receptor transactivation activity and male urethra morphogenesis. J Biol Chem 285, 27776-27784 (2010). PMC2934645

Sanchez, E. R. Chaperoning Physiology: The In Vivo Roles of Hsp90 and Its Cochaperones. BBA - Molecular Cell Research Epub ahead of print, (2011).

Stechschulte, L. A. & Sanchez, E. R. FKBP51-a selective modulator of glucocorticoid and androgen sensitivity. Curr Opin Pharmacol (2011).

Last Updated: 3/22/15