Dale B. Hales

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Southern Illinois University
Medicine
Physiology
ChairAppointed: 2009
Southern Illinois University
Medicine
Obstetrics & Gynecology
ProfessorAppointed: 2009
Professional Headshot of Dale B. Hales

Mailing Address

Life Science II, Room 250
Mail Code: 6512
Department of Physiology
Southern Illinois University
Carbondale, Illinois 62901
United States

Contact Information

Phone: (618) 453-1544
Fax: (618) 453-1517
dhales@siumed.edu

Qualifications

Ph.D..

Expertise and Research Interests

Role of inflammation and oxidative stress in the etiology of hormonal carcinogenesis

Prevention and treatment of ovarian cancer with functional food based diets (flax seed) rich in omega-3 fatty acids

Chicken as a model for human disease

Immune-endocrine control of male reproductive function
Regulation of steroidogenic enzyme gene expression in Leydig cells

Impact of the environment on reproductive processes
Role of oxidative stress in regulation of reproductive function

Other Expertise

Mitochondrial biology
Adrenal physiology

Future Research

Use of the chicken model of ovarian cancer to elucidate the origin of high-grade serous pelvic carcinoma to determine the role of the oviduct vs ovarian surface epithelium.

Our exploration into immune modulation of Leydig cell steroidogenesis revealed that oxidative stress related perturbation of Leydig cell mitochondria mediates the abrupt cessation of testosterone production at the level of cholesterol transfer to the steroidogenic pathway. This mechanism is central to a host of pathologies known to present with hypogonadism including alcoholism, diabetes, aging and certain environmental endocrine disruptors. Our laboratory has initiated studies in oxidative stress effects of alcoholism, diabetes and aging as well as environmental agro and industrial compounds such as dioxin, polycyclic armoatic hydrocarbons, and conazoles.

Industrial Relevance

Dietary intervention with natural products for the prevention and treatment of ovarian cancers.

Therapeutic intervention for workplace exposure to endocrine disruptors that cause decreased testosterone

Keywords

COS Keywords:

Biochemistry, Cytokines, Endocrinology, Gene Expression, Gene Regulation, Inflammation, Molecular Biology, Oxidative Stress, Physiology, Reproductive Endocrinology.

Additional Terms:

Biochemistry, Cancer, Cytokine, Endocrinology, Inflammation, Leydig Cell, Mitochondria, Molecular Biology, Ovary, Oxidative Stress, Physiology, Reactive Oxygen Species, Steroidogenesis, Testosterone.

Memberships

American Association for the Advancement of Science
American Physiological Society
American Society for Biochemistry and Molecular Biology
American Society for Reproductive Immunology
Association of Physiology Department Chairs
Endocrine Society
Mitochondrial Research Society
Society for the Study of Reproduction

Previous Positions

2007-2009, Professor, University of Illinois at Chicago, College of Medicine, Physiology & Biophysics
1995-2007, Associate Professor, University of Illinois at Chicago, College of Medicine, Physiology & Biophysics
1989-1995, Assistant Professor, University of Illinois at Chicago, College of Medicine, Physiology and Biophysics
1985-1989, Post-doctoral fellow, University of Michigan, Biological Chemistry
1983-1985, Research Fellow, University of Colorado at Boulder, Pharmacy, Pharmacy

Funding Received

  • NCI: "Dietary Intervention in the Gallus Domesticus Model of Ovarian Cancer", $155,000, 2008 to 2010.
  • NCCAM: "Flax seed therapy for the prevention of ovarian cancer.", $426,250, 2007 to 2010.
  • United States Department of Defense (DOD): "CYP1B1, oxidative stress, and inflammation in the etiology of ovarian epithelial cancer using an avian model of ovarian carcinoma, $300,000, 2005 to 2007.
  • American Cancer Society (ACS): CYP1B1, Oxidative Stress and Prostate Cancer, 100,000, 2004 to 2006.
  • National Institutes of Health (NIH): "Mechanisms of Estrogen Biosynthesis in Endometriosis, Co-Investigator (Ser, 2004 to 2009.
  • NICHD U-54 Director, histology core: Center for Women's Health and Reproduction, 7,000,000, 2002 to 2007.

Publications

  • Locke JA, Fazli L, Adomat H, Smyl J, Weins K, Lubik AA, Hales DB, Nelson CC, Gleave ME, Tomlinson Guns ES (Jun 2009) A novel communication role for CYP17A1 in the progression of castration-resistant prostate cancer., The Prostate, 69 (9), 928-37 Abstract
  • Ansenberger K, Zhuge Y, Lagman JA, Richards C, Barua A, Bahr JM, Hales DB (Jun 2009) E-cadherin expression in ovarian cancer in the laying hen, Gallus domesticus, compared to human ovarian cancer., Gynecologic oncology, 113 (3), 362-9 Abstract
  • Barua A, Edassery SL, Bitterman P, Abramowicz JS, Dirks AL, Bahr JM, Hales DB, Bradaric MJ, Luborsky JL (May 2009) Prevalence of antitumor antibodies in laying hen model of human ovarian cancer., International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 19 (4), 500-7 Abstract
  • Barua A, Bitterman P, Abramowicz JS, Dirks AL, Bahr JM, Hales DB, Bradaric MJ, Edassery SL, Rotmensch J, Luborsky JL (May 2009) Histopathology of ovarian tumors in laying hens: a preclinical model of human ovarian cancer., International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 19 (4), 531-9 Abstract
  • Attar E, Tokunaga H, Imir G, Yilmaz MB, Redwine D, Putman M, Gurates B, Attar R, Yaegashi N, Hales DB, Bulun SE (Feb 2009) Prostaglandin E2 via steroidogenic factor-1 coordinately regulates transcription of steroidogenic genes necessary for estrogen synthesis in endometriosis., The Journal of clinical endocrinology and metabolism, 94 (2), 623-31 Abstract
  • Zhuge Y, Lagman JA, Ansenberger K, Mahon CJ, Daikoku T, Dey SK, Bahr JM, Hales DB (Jan 2009) CYP1B1 expression in ovarian cancer in the laying hen Gallusdomesticus., Gynecologic oncology, 112 (1), 171-8 Abstract
  • Hales DB, Zhuge Y, Lagman JA, Ansenberger K, Mahon C, Barua A, Luborsky JL, Bahr JM (Jun 2008) Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus)., Endocrine, 33 (3), 235-44 Abstract
  • Stammer K, Edassery SL, Barua A, Bitterman P, Bahr JM, Hales DB, Luborsky JL (Apr 2008) Selenium-Binding Protein 1 expression in ovaries and ovarian tumors in the laying hen, a spontaneous model of human ovarian cancer., Gynecologic oncology, 109 (1), 115-21 Abstract
  • Hales, DB (2007) . "Regulation of Leydig Cell Function as it Pertains to the Inflammatory Response" In Payne, AH, Hardy, MP (eds), Contemporary Endocrinology:The Leydig Cell in Health and Disease, Towato, NJ, Humana Press, 305-321 pages (bookchapter)
  • Allen JA, Shankara T, Janus P, Buck S, Diemer T, Hales KH, Hales DB (Aug 2006) Energized, polarized, and actively respiring mitochondria are required for acute Leydig cell steroidogenesis., Endocrinology, 147 (8), 3924-35 Abstract
  • Hedger, MP, Hales, DB (2006) Reproductive Immunology of the Male" In Neil, J (eds), Physiology of Reproduction, 3rd edition, San Diego, Elsevier, 1195-1286 pages (bookchapter)
  • Hales DB, Allen JA, Shankara T, Janus P, Buck S, Diemer T, Hales KH (Dec 2005) Mitochondrial function in Leydig cell steroidogenesis., Annals of the New York Academy of Sciences, 1061, 120-34 Abstract
  • Hauet T, Yao ZX, Bose HS, Wall CT, Han Z, Li W, Hales DB, Miller WL, Culty M, Papadopoulos V (Feb 2005) Peripheral-type benzodiazepine receptor-mediated action of steroidogenic acute regulatory protein on cholesterol entry into leydig cell mitochondria., Molecular Endocrinology (baltimore, Md.), 19 (2), 540-54 Abstract
  • Allen JA, Diemer T, Janus P, Hales KH, Hales DB (Dec 2004) Bacterial endotoxin lipopolysaccharide and reactive oxygen species inhibit Leydig cell steroidogenesis via perturbation of mitochondria., Endocrine, 25 (3), 265-75 Abstract
  • Allen JA, Diemer T, Janus P, Hales KH, Hales DB (Dec 2004) Bacterial endotoxin lipopolysaccharide and reactive oxygen species inhibit Leydig cell steroidogenesis via perturbation of mitochondria., Endocrine, 25 (3), 265-75 Abstract
  • Payne AH, Hales DB (Dec 2004) Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones., Endocrine Reviews, 25 (6), 947-70 Abstract
  • Fleury A, Mathieu AP, Ducharme L, Hales DB, LeHoux JG (Aug 2004) Phosphorylation and function of the hamster adrenal steroidogenic acute regulatory protein (StAR)., The Journal of Steroid Biochemistry and Molecular Biology, 91 (4-5), 259-71 Abstract
  • Selvage DJ, Hales DB, Rivier CL (Mar 2004) Comparison between the influence of the systemic and central injection of alcohol on Leydig cell activity., Alcoholism, Clinical and Experimental Research, 28 (3), 480-8 Abstract
  • Benmessahel Y, Troadec JD, Cadepond F, Guennoun R, Hales DB, Schumacher M, Groyer G (Feb 2004) Downregulation of steroidogenic acute regulatory protein (StAR) gene expression by cyclic AMP in cultured Schwann cells., Glia, 45 (3), 213-28 Abstract
  • LeHoux JG, Fleury A, Ducharme L, Hales DB (Feb 2004) Phosphorylation of the hamster adrenal steroidogenic acute regulatory protein as analyzed by two-dimensional polyacrylamide gel electrophoreses., Molecular and Cellular Endocrinology, 215 (1-2), 127-34 Abstract
  • Granot Z, Geiss-Friedlander R, Melamed-Book N, Eimerl S, Timberg R, Weiss AM, Hales KH, Hales DB, Stocco DM, Orly J (Dec 2003) Proteolysis of normal and mutated steroidogenic acute regulatory proteins in the mitochondria: the fate of unwanted proteins., Molecular Endocrinology (baltimore, Md.), 17 (12), 2461-76 Abstract
  • Provost AC, Pequignot MO, Sainton KM, Gadin S, Salle S, Marchant D, Hales DB, Abitbol M (Sep 2003) Expression of SR-BI receptor and StAR protein in rat ocular tissues., Comptes Rendus Biologies, 326 (9), 841-51 Abstract
  • Sierra A, Lavaque E, Perez-Martin M, Azcoitia I, Hales DB, Garcia-Segura LM (Sep 2003) Steroidogenic acute regulatory protein in the rat brain: cellular distribution, developmental regulation and overexpression after injury., The European Journal of Neuroscience, 18 (6), 1458-67 Abstract
  • Diemer T, Allen JA, Hales KH, Hales DB (Jul 2003) Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis., Endocrinology, 144 (7), 2882-91 Abstract
  • Jirawatnotai S, Moons DS, Stocco CO, Franks R, Hales DB, Gibori G, Kiyokawa H (May 2003) The cyclin-dependent kinase inhibitors p27Kip1 and p21Cip1 cooperate to restrict proliferative life span in differentiating ovarian cells., The Journal of Biological Chemistry, 278 (19), 17021-7 Abstract
  • Diemer T, Hales DB, Weidner W (Feb 2003) Immune-endocrine interactions and Leydig cell function: the role of cytokines., Andrologia, 35 (1), 55-63 Abstract
  • Sorianello E, Fritz S, Beyer C, Hales DB, Mayerhofer A, Libertun C, Lux-Lantos V, Development of an experimental ovarian tumor: immunocytochemical analysis, European Journal of Endocrinology / European Federation of Endocrine Societies., 147(3), 387-95, September 2002 Abstract
  • Salvador LM, Maizels E, Hales DB, Miyamoto E, Yamamoto H, Hunzicker-Dunn M, Acute signaling by the LH receptor is independent of protein kinase C activation, Endocrinology, 143(8), 2986-94, Aug 2002 Abstract
  • Hales DB, Another piece in the maddening puzzle of declining steroidogenesis in aging Leydig cells, Journal of Andrology, 23(3), 327-8; discussion 32, 2002 Abstract
  • Shea-Eaton W, Sandhoff TW, Lopez D, Hales DB, McLean MP, Transcriptional repression of the rat steroidogenic acute regulatory (StAR) protein gene by the AP-1 family member c-Fos, Molecular and Cellular Endocrinology, 188(1-2), 161-70, February 2002 Abstract
  • Moons DS, Jirawatnotai S, Tsutsui T, Franks R, Parlow AF, Hales DB, Gibori G, Fazleabas AT, Kiyokawa H, Intact follicular maturation and defective luteal function in mice deficient for cyclin- dependent kinase-4, Endocrinology, 143(2), 647-54, February 2002 Abstract
  • Hales DB (Oct-Nov 2002) Testicular macrophage modulation of Leydig cell steroidogenesis., Journal of Reproductive Immunology, 57 (1-2), 3-18 Abstract
  • Artemenko IP, Zhao D, Hales DB, Hales KH, Jefcoate CR, Mitochondrial processing of newly synthesized steroidogenic acute regulatory protein (StAR), but not total StAR, mediates cholesterol transfer to cytochrome P450 side chain cleavage enzyme, Journal of Biological Chemistry, 276(49), 46583-96, December 2001 Abstract
  • Wang ZJ, Jeffs B, Ito M, Achermann JC, Yu RN, Hales DB, Jameson JL, Aromatase (Cyp19) expression is up-regulated by targeted disruption of Dax1, Proceedings of the National Academy of Sciences (USA), 98(14), 7988-93, July 2001 Abstract
  • Hales DB, Editorial: gonadal-specific transcription factors--gata (go) 4 it!, Endocrinology, 142(3), 974-6, March 2001 Abstract
  • Fritz S, Grunert R, Stocco DM, Hales DB, Mayerhofer A, StAR protein is increased by muscarinic receptor activation in human luteinized granulosa cells, Molecular and Cellular Endocrinology, 171(1-2), 49-51, Jan 2001 Abstract
  • Cascio C, Brown RC, Liu Y, Han Z, Hales DB, Papadopoulos V, Pathways of dehydroepiandrosterone formation in rat brain glia, Journal of Steroid Biochemistry and Molecular Biology, 75(2-3), 177-86, December 2000 Abstract
  • Hales KH, Diemer T, Ginde S, Shankar BK, Roberts M, Bosmann HB, Hales DB, Diametric effects of bacterial endotoxin lipopolysaccharide on adrenal and Leydig cell steroidogenic acute regulatory protein, Endocrinology, 141(11), 4000-12, November 2000 Abstract
  • Diemer T, Ludwig M, Huwe P, Hales DB, Weidner W, Influence of urogenital infection on sperm function., Curr Opin Urol, 10(1), 39-44, 2000 Abstract
  • Hales, DB (2000) ."Cytokines and Testicular Function" in Cytokines and Reproduction " In Hill, JA (eds), Cytorkines in Reproduction, NY, John Wiley & Sons, 17-42 pages (bookchapter)
  • Lehoux JG, Hales DB, Fleury A, Briere N, Martel D, Ducharme L, The in vivo effects of adrenocorticotropin and sodium restriction on the formation of the different species of steroidogenic acute regulatory protein in rat adrenal, Endocrinology, 140(11), 5154-64, November 1999 Abstract
  • Fiedler EP, Plouffe L Jr, Hales DB, Hales KH, Khan I, Prostaglandin F(2alpha) induces a rapid decline in progesterone production and steroidogenic acute regulatory protein expression in isolated rat corpus luteum without altering messenger ri, Biology of Reproduction, 61(3), 643-50, September 1999 Abstract
  • Hales DB, Diemer T, Hales KH, Role of cytokines in testicular function., Endocrine, 10(3), 201-17, June 1999 Abstract
  • Sam AD 2nd, Sharma AC, Lee LY, Hales DB, Law WR, Ferguson JL, Bosmann HB, Sepsis produces depression of testosterone and steroidogenic acute regulatory \(StAR\) protein., Shock, 11(4), 298-301, April 1999 Abstract
  • Sandhoff TW, Hales DB, Hales KH, McLean MP, Transcriptional regulation of the rat steroidogenic acute regulatory protein gene by steroidogenic factor 1, Endocrinology, 139(12), 4820-31, December 1998 Abstract
  • Fleury A, Ducharme L, Hales DB, Stocco DM, LeHoux JG, Acute in vivo effects of ACTH on the expression of steroidogenic acute regulatory protein in rat adrenal, Endocrine Research, 24(3-4), 571-4, 1998 Abstract
  • Sharma AC, Sam AD 2nd, Lee LY, Hales DB, Law WR, Ferguson JL, Bosmann HB, Effect of NG-nitro-L-arginine methyl ester on testicular blood flow and serum steroid hormones during sepsis, Shock (augusta, Ga.), 9(6), 416-21, June 1998 Abstract
  • Hales DB, Greene R, Arginine vasopressin inhibition of cytochrome P450c17 and testosterone production in mouse Leydig cells, Endocrine, 8(1), 19-28, February 1998 Abstract
  • Ronen-Fuhrmann T, Timberg R, King SR, Hales KH, Hales DB, Stocco DM, Orly J, Spatio-temporal expression patterns of steroidogenic acute regulatory protein (StAR) during follicular development in the rat ovary, Endocrinology, 139(1), 303-15, Jan 1998 Abstract
  • Xiong Y, Hales DB, Differential effects of tumor necrosis factor-alpha and interleukin-1 on 3 beta-hydroxysteroid dehydrogenase/delta 5-->delta 4 isomerase expression in mouse Leydig cells, Endocrine, 7(3), 295-301, December 1997 Abstract
  • Clark BJ, Combs R, Hales KH, Hales DB, Stocco DM, Inhibition of transcription affects synthesis of steroidogenic acute regulatory protein and steroidogenesis in MA-10 mouse Leydig tumor cells, Endocrinology, 138(11), 4893-901, November 1997 Abstract
  • Li X, Hales KH, Watanabe G, Lee RJ, Pestell RG, Hales DB, The effect of tumor necrosis factor-alpha and cAMP on induction of AP-1 activity in MA-10 tumor Leydig cells., Endocrine, 6(3), 317-24, 1997 Abstract
  • Bosmann HB, Hales KH, Li X, Liu Z, Stocco DM, Hales DB, Acute in vivo inhibition of testosterone by endotoxin parallels loss of steroidogenic acute regulatory (StAR) protein in Leydig cells, Endocrinology, 137(10), 4522-5, October 1996 Abstract
  • Sharma AC, Bosmann HB, Motew SJ, Hales KH, Hales DB, Ferguson JL, Steroid hormone alterations following induction of chronic intraperitoneal sepsis in male rats, Shock (augusta, Ga.), 6(2), 150-4, August 1996 Abstract
  • McLean MP, Warden KJ, Sandhoff TW, Irby RB, Hales DB, Altered ovarian sterol carrier protein expression in the pregnant streptozotocin-treated diabetic rat, Biology of Reproduction, 55(1), 38-46, July 1996 Abstract
  • Naaman-Reperant E, Hales DB, Durand P, Effect of transforming growth factor beta-1 on the cholesterol side-chain cleavage system in the adrenal gland of sheep fetuses and newborns, Endocrinology, 137(3), 886-92, March 1996 Abstract
  • Hales, DB (1996) . "Macrophage-Leydig Cell Interactions: An Overview" In Payne, AH, Hardy, MP, Russell, LD (eds), The Leydig Cell, Vienna, IL, Cache River Press, 451-466 pages (bookchapter)
  • Li X, Youngblood GL, Payne AH, Hales DB, Tumor necrosis factor-alpha inhibition of 17 alpha-hydroxylase/C17-20 lyase gene \(Cyp17\) expression., Endocrinology, 136(8), 3519-26, 1995 Abstract
  • Xiong Y, Hales DB, Expression, regulation, and production of tumor necrosis factor-alpha in mouse testicular interstitial macrophages in vitro, Endocrinology, 133(6), 2568-73, December 1993 Abstract
  • Hales DB, Interleukin-1 inhibits Leydig cell steroidogenesis primarily by decreasing 17 alpha-hydroxylase/C17-20 lyase cytochrome P450 expression, Endocrinology, 131(5), 2165-72, November 1992 Abstract
  • Durkee TJ, McLean MP, Hales DB, Payne AH, Waterman MR, Khan I, Gibori G, P450(17 alpha) and P450SCC gene expression and regulation in the rat placenta, Endocrinology, 130(3), 1309-17, March 1992 Abstract
  • Hales DB, Sha L, Payne AH, Glucocorticoid and cyclic adenosine 3'5'-monophosphate-mediated induction of cholesterol side-chain cleavage cytochrome P450 (P450scc) in MA-10 tumor Leydig cells. Increases in mRNA are cy, Endocrinology, 126(6), 2800-8, June 1990 Abstract
  • Hales DB, Payne AH, Glucocorticoid-mediated repression of P450scc mRNA and de novo synthesis in cultured Leydig cells, Endocrinology, 124(5), 2099-104, May 1989 Abstract
  • Hales DB, Ho B, Thompson JA, Inter- and intramolecular deuterium isotope effects on the cytochrome P-450-catalyzed oxidative dehalogenation of 1,1,2,2-tetrachloroethane, Biochemical and Biophysical Research Communications, 149(2), 319-25, December 1987 Abstract
  • Payne AH, Anakwe OO, Hales DB, Georgiou M, Perkins LM, Quinn PG, Regulation of mitochondrial and microsomal cytochrome P-450 enzymes in Leydig cells, Advances in Experimental Medicine and Biology, 219, 467-87, 1987 Abstract
  • Payne, A.H, Anakwe, O.O, Hales, D.B., Georgiou, M, Perkins, L.M, Quinn, P.G. (1987) "Regulation of Mitochondrial and Microsomal Cytochrome P-450 enzymes in Leydig cells." In Mahesh, V.B, Dhindsa, D.S, Anderson, E.,, Kalra, S.P (eds), Regulation of Ovarian and Testicular Function, NY, Plenum Press, N.Y, 467-487 pages (bookchapter)
  • Hales DB, Betz G, NADPH-cytochrome P-450 reductase from untreated rat testicular and liver microsomes: isolation and comparison, Endocrinology, 119(2), 811-8, August 1986 Abstract
  • Hales DB, Betz G, Steroid interactions with cytochrome P-450 from testis microsomes, Journal of Steroid Biochemistry, 21(6), 639-42, December 1984 Abstract
  • Betz G, Tsai P, Hales D, Reconstitution of steroid 17,20-lyase activity after separation and purification of cytochrome P-450 and its reductase from rat testis microsomes, Endocrinology, 107(4), 1055-60, October 1980 Abstract

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Last Updated: 9/2/2009

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