Physiology and Pharmacology

Terry D. Hinds, Jr., Ph.D.

t hinds    

      

Assistant Professor

Phone: (419) 383-4465
Fax: (419-383-2871

E-mail: Terry.Hinds@utoledo.edu

 

Research Interests:

My lab focuses on the involvement of the heme oxygenase (HO) system and nuclear receptors in metabolic diseases, which includes obesity and diabetes as well as cancer.  The HO system maintains metabolic balance by signaling to biliverdin reductase that produces the antioxidant, bilirubin.  My lab looks at the how HO, bilirubin, and nuclear receptors signal for balance in metabolic disorders.  We are currently studying how bilirubin can aid the nutrient and lipid sensing nuclear receptors, the PPARs (PPAR alpha, PPAR gamma, and PPAR delta), in the maintenance of metabolic homeostasis. Other nuclear receptors are stress sensing, such as the glucocorticoid receptors (GRalpha and GR beta), which regulate the immune system balance and glucose production during times of stress.  Together, the PPARs and GRs regulate the balance of lipids and glucose as well as maintain growth of cancer cells.

Current studies:

Project 1: 
We are working on drug targeting of the heme oxygenase system in the prevention of obesity and the link between fat tissue in obesity-induced hypertension.  Diet induced obesity results in elevated levels of glucose and fatty acids in blood, liver and fat tissues, resulting in the enhanced production of reactive oxygen species (ROS).  The oxidative stress magnifies the adverse effects of obesity by inducing inflammation of tissues, leading to the development of non-alcoholic fatty liver disease (NAFLD) as well as vascular dysfunction.

Project 2:  We are looking at the role of the glucocorticoid receptors in prostate and bladder cancer.  This is a clinical investigation in collaboration with the UT Department of Urology and Department of Pathology, which includes analysis of human specimens taken from patients at the University of Toledo Health Center.  We have been screening human cancer samples for expression of the GR isoforms, in which, one may be linked to metastasis.  In these studies, we are also using human cancer cells to understand the involvement of the receptors in cancer and drug targeting.  Interestingly, we have discovered that metabolic growth factors such as insulin and epidermal growth factor enhance the expression of the receptor and lead to exacerbated growth.  We are currently looking at drugs that can inhibit the function of the GR isoform that leads to growth.

Project 3:  In our newest study, we are analyzing the biliverdin reductase (BVRA and BVRB) in metabolic disorders such as obesity and diabetes, and potential drug targeting of the enzymes.  On this project, we are collaborating with the University of Mississippi Medical Center as well as the Center for Drug Design and Development, which are building us new drug compounds that can target the BVR isozymes as well as nuclear receptors in the prevention of obesity and diabetes.  This project is of novel drug design that may lead to a new class of drugs known as THin Molecules.


Awards and Commendations:


2014                President of the Ohio Physiological Society
2014                Research Scientist Development Award (K01) NIH/NHLBI
2014                NIH LRP Award for Health Disparities Research
2013                NIH NHLBI program, PRIDE-Functional and Applied Genomic of Blood Disorders
2010                Selected for Oral Presentation in “Hot topics of Physiology”, Keystone Symposia,
                        Nuclear Receptors: Signaling, Gene Regulation and Cancer, Keystone, CO
2010                Cancer, Genetics, and Signaling (CGS) Group at the National Cancer Institute-Frederick.
                        Selected in Top 10 at the NIH Graduate Student Research Festival (200 total).
2010                Abstract Award, Endocrine Society National Meeting, San Diego, CA
2009-10           Ruth L. Kirschstein National Research Service Award (NRSA), NIDDK, NIH
2001                Thinker of the Year Award Recipient, Civic Development Group


Patents:

For: Methods and Compositions for Treating Dyslipidemia and Obesity using Protein Phosphatase 5 as a Drug Target (2012).
          Inventors: Terry D. Hinds, Jr. and Edwin R. Sanchez
          *US Utility Patent
          http://utoledo.technologypublisher.com/technology/11187 

For: Glucocorticoid Receptor Beta in Mice (2010). 
          Inventors: Terry D. Hinds, Jr. and Edwin R. Sanchez
          *Provisional Patent


Licensing:

          Resource: Mouse Glucocorticoid Receptor beta Polyclonal Antibody
          Inventors: Terry D. Hinds, Jr. and Edwin R. Sanchez
          http://utoledo.technologypublisher.com/technology/11366


Appointments:

2013 - Assistant Professor, Tenure Track, Physiology & Pharmacology, University of Toledo
2012 - Instructor, Organ Systems course in Physiology & Pharmacology, University of Toledo
2010 - Postdoctoral Fellow, Physiology & Pharmacology, University of Toledo
2007 - Guest lecturer for Methods in Molecular Biology course, Medical University of Ohio
2004 - Anatomy and Physiology I & II, Adjunct Instructor, Shawnee State University


Editorial Board Member:

Diabetes Research - Open Journal                   2014
Obesity Research - Open Journal                     2014


Representative Publications:

Luke O’Brien, Pete Hosick, Kezia John, David Stec, and Terry D. Hinds, Jr.  Biliverdin Reductase Isozymes in Metabolism. Trends in Endocrinology and Metabolism. (2015).  PMID: 25726384.

Terry D. Hinds, Jr., Lance Stechschulte , Fadel Elkhairi, and Edwin Sanchez.  Analysis of FK506, Timcodar (VX-853) and FKBP51 and FKBP52 Chaperones in Control of Glucocorticoid Receptor Activity and Phosphorylation.  Pharmacology Research & Perspectives (2014).  PMID: 25505617.

Lance A. Stechschulte, Terry D. Hinds, Jr., Saja S. Khuder, Weinian Shou, Sonia M. Najjar, and Edwin R. Sanchez.  FKBP51 Controls Cellular Adipogenesis Through p38 Kinase-mediated Phosphorylation of GRα and PPARγ.  Molecular Endocrinology (2014).  PMID: 24933247.

Lance A. Stechschulte, Terry D. Hinds, Jr., Simona S. Ghanem, Weinian Shou, Sonia M. Najjar, and Edwin R. Sanchez. FKBP51 Reciprocally Regulates GRα and PPARγ Activation via the Akt-p38 Pathway.  Molecular Endocrinology (2014).  PMID: 24933248.

Lance A. Stechschulte, Leah Wuescher, Joseph Marino, Jennifer Hill, Charis Eng, and Terry D. Hinds, Jr.  Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN.  J Biol Chem (2014).  PMID: 24817119.

Joseph S Marino, Terry D Hinds, Rachael Hoover, Eric Ondrus, Jeremy L Onion, Abigail Dowling, Thomas J McLoughlin, Edwin R Sanchez and Jennifer W Hill.  Suppression of Protein Kinase C Theta Contributes to Enhanced Myogenesis in vitro via IRS1 and ERK1/2 phosphorylation.  BMC Cell Biology (2013). PMID: 24053798

Terry D. Hinds, Jr., Charles Meadows, Komal Sodhi, Larisa Fedorova, Dong Hyun Kim, Nitin Puri, Joseph Shapiro, Nader G. Abraham and Attallah Kappas.  Increased HO-1 Levels Ameliorate the Development of Fatty Liver Via Reduction of Heme.  Obesity (2013).  PMID: 23839791.

Komal Sodhi, Nitin Puri, Dong Hyun Kim, Terry D. Hinds, Jr., Lance A. Stechschulte, Gaia Favero, Luigi Rodella, Joseph Shapiro, David Jude, and Nader Abraham.  PPAR-delta Binding to Heme Oxygenase 1 Promoter Prevents Angiotensin II Induced Adipocyte Dysfunction in Goldblatt Hypertensive Rats. International Journal of Obesity (2013).  PMID: 23779049.

Larisa V. Fedorova, Komal Sodhi, Cara Gatto-Weis, Nitin Puri, Terry D. Hinds, Jr., Joseph I. Shapiro, Deepak Malhotra.  Peroxisome proliferator-activated receptor-delta agonist, HPP593, prevents renal necrosis under chronic ischemia.  PLoS ONE (2013).  PMID: 23691217.

Luca Vanella, Komal Sodhi, Dong Hyun Kim, Nitin Puri, Mani Maheshwari, Terry D. Hinds, Jr., Lars Bellner, D. Goldstein, Stephen J. Peterson, Nader G. Abraham and Joseph Shapiro.  Increased Heme-Oxygenase 1 Expression Diminished Adipocyte Differentiation and Lipid Accumulation by Upregulation of the Canonical Wnt Signaling Cascade.  Stem Cell Research and Therapy (2013).  PMID: 23497794.

Terry D. Hinds, Jr., Stechschulte, L. A., Cash, H. A., Whisler, D., Banerjee, A., Yong, W., Khuder, S. S., Kaw, M. K., Shou, W., Najjar, S. M. & Sanchez, E. R.  Protein phosphatase 5 mediates lipid metabolism through reciprocal control of glucocorticoid and PPAR{gamma} receptors.  J Biol Chem (2011). PMID: 21994940.

Wuescher, L., Angevine, K., Terry D. Hinds, Jr., Ramakrishnan, S., Najjar, S., and Mensah-Osman, E.  Insulin regulates Menin expression, cytoplasmic localization and interaction with FOXO1.  Am J Phys Endo & Met (2011).  PMID: 21693693.

Chen, H., Yong, W., Terry D. Hinds, Jr., 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).  PMID: 20605780.

Terry D. Hinds, Jr., 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).  PMID: 20660300.

Periyasamy, S., Terry D. Hinds, Jr., 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).  PMID: 20023700.

Warrier, M., Terry D. Hinds, Jr., 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).  PMID: 20427484.

Wolf, I. M., Periyasamy, S., Terry D. Hinds, Jr., Jr., Yong, W., Shou, W. & Sanchez, E. R.  Targeted ablation reveals a novel role of FKBP52 in gene-specific regulation of glucocorticoid receptor transcriptional activity.  J Steroid Biochem Mol Biol 113, 36-45 (2009).  PMID: 19073255.

Banerjee, A., Periyasamy, S., Wolf, I. M., Terry D. Hinds, Jr., Yong, W., Shou, W. & Sanchez, E. R.  Control of glucocorticoid and progesterone receptor subcellular localization by the ligand-binding domain is mediated by distinct interactions with tetratricopeptide repeat proteins.  Biochemistry 47, 10471-10480 (2008).  PMID: 18771283.

Terry D. Hinds, Jr. & Edwin R. Sanchez.  Protein phosphatase 5. Int J Biochem Cell Biol 40 (11), 2358-2362 (2008).  PMID: 17951098.

E. Uldrich, R. Phipps, Terry D. Hinds, Jr. and Eugene H. Burns, Jr. 2004.  Selective reduction of coliforms in constructed wetlands.  In: Mitsch, W. J. and V. Bouchard (ed.), Olentangy River Wetland Research Park at The Ohio State University, Annual Report. Columbus, OH.

Terry D. Hinds, Jr., Rachel R. Brown, and Eugene H. Burns, Jr. 2002.  Reduction of Fecal Coliform Levels in Two Constructed Wetlands at the Olentangy River Wetland Research Park.  In: Mitsch, W. J. and V. Bouchard (ed.), Olentangy River Wetland Research Park at The Ohio State University, Annual Report. Columbus, OH.

Last Updated: 6/26/15