Physiology and Pharmacology

Jennifer Hill, Ph.D.

Hill

Assistant Professor

Phone:  419-383-6137
Fax:      419-383-2871

E-mail:  Jennifer.Hill4@utoledo.edu

Curriculum Vitae

Education and Training

  • Williams College, MA.  B.A., Biology, 1997
  • Northwestern University, IL.  Ph.D., Neuroscience, 2003
  • Beth Israel Deaconess Medical Center, MA.  Post-Doctoral Fellow, 2003-2005
  • UT Southwestern Medical Center, TX.  Post-Doctoral Fellow/Instructor, 2006-2009

Appointments

  • UT Southwestern Medical Center, Dallas, TX.  Instructor, Division of Hypothalamic Research, Department of Internal Medicine, 2007-2009
  • Toledo, OH.  Assistant Professor, Center for Diabetes and Endocrine Research (CeDER), Department of Physiology & Pharmacology, University of Toledo, College of Medicine, 2009

Honors and Awards

  • Michigan Diabetes Research Pilot & Feasibility Study Grant, January 2014
  • Young Investigator Award, Sigma Xi, 2013
  • Young Investigator Award, Endocrine Society, 2013
  • NICHD R21 Grant in Reproductive Endocrinology, HD071529, 2012
  • NICHD K99/R00 Grant in Neuroendocrinology, R00HDO56491, 2009
  • NIH LRP Award for Fertility and Contraception Research, 2007

Service and Society Memberships

  • External Expert Reviewer for NICHD Fertility and Infertility Branch U54 Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR) Program
  • Frontiers in Systems and Translational Endocrinology, Guest Associate Editor
  • Ad-hoc Journal Reviewer:  BBA Molecular Basis of Disease, Cell Metabolism, Cell & Tissue Research, Endocrine, Endocrinology, Experimental and Clinical Endocrinology & Diabetes, Frontiers in Neuroendocrinology, Neuroendocrinology, Neuropeptides, Obesity, Physiological Genomics, PLoS One, Reproductive Sciences
  • Society for Neuroscience (SFN), Member
  • Endocrine Society, Member
  • American Diabetes Association, Member

Research Interests

My laboratory’s interests lie in understanding hypothalamic homeostatic mechanisms controlling body weight and fertility and the interactions between these two systems. The brain blocks reproduction in animals under metabolic stress. Within the hypothalamus, energy deficits suppress gonadotropin-releasing hormone (GnRH) release from a sub-population of neurons that maintain fertility. Anorexia, cachexia, and excessive exercise suppress reproductive cyclicity in humans and with it the estrogen release essential for bone health. Fully 5% of women of reproductive age suffer from infertility related to eating disorders. Furthermore, the incidence of exercise-related anovulation may reach as high as 61% in gymnasts and 78% in runners. On the opposite end of the spectrum, obesity and diabetes also negatively affect fertility. As rates of these diseases rise, it is urgent that we unravel the hypothalamic homeostatic mechanisms controlling body weight and fertility and the interactions between these two systems.

The hypothesis underlying my research is that circulating metabolic factors (such as leptin, insulin, ghrelin, glucose, LC-FAs or PYY3-36) are perceived directly or indirectly by GnRH neurons of the hypothalamus and convey information that prevents GnRH release during a state of negative energy balance.  Determining the mechanisms behind this metabolic-reproductive connection will provide much needed targets for medical treatment. The cornerstone of my laboratory’s efforts is timed, targeted genetic manipulation using the power of tissue-specific gene deletion. Combined with anatomical, electrophysiological, and physiological techniques this approach offers a powerful tool for investigating the hypothalamic control of metabolism and fertility.

Publications

  • Stechschulte LA, Wuescher L, Marino JS, Hill JW, Eng C, Hinds TD Jr.  Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN. J Biol Chem. 2014 May 9. [Epub ahead of print] PMID: 24817119 
  • Dowling AR, Nedorezov LB, Qiu X, Marino JS, Hill JW.  Genetic factors modulate the impact of pubertal androgen excess on insulin sensitivity and fertility.  PLos One 2013; November 20; 8:(11):e79849.  PMID: 24278193
  • Makani V, Sultana R, Sie KS, Orjiako D, Tatangelo M, Dowling A, Cai J, Pierce W, Butterfield DA, Hill J, Park J.  Annexin A1 Complex Mediates Oxytocin Vesicle Transport.  J Neuroendocrinol 2013 Oct 3; PMID: 24118254
  • Marino JS, Hinds TD, Hoover R, Ondrus E, Onion JL, Dowling A, McLoughlin TJ, Hill JW.  Suppression of Protein Kinase C Theta Contributes to Enhanced Myogenesis in vitro via IRS1 and ERK1/2 phosphorylation.  BMC Cell Biology 2013; 14:39.
  • Hill, JW, Alreja, M, Elias, CF.  From precocious puberty to infertility: metabolic control of the reproductive function.  Frontiers in Systems and Translational Endocrinology April 2013 PMID: 23565110.  Invited Review.
  • Qiu, X., Dowling, A., Marino J., Faulkner L., Brüning, J., Elias, CF, Bryant, B., Hill, JW.  Delayed Puberty but Normal Fertility in Mice with Selective Deletion of Insulin Receptors from Kiss1 Cells.  Endocrinology 2013 Mar;154(3):1337-48 PMID: 23392256
  • Hill, JW.  PVH Pathways Controlling Energy Homeostasis.  Indian Journal of Endocrinology and Metabolism 2012 Dec;16(Suppl 3):S627-636. PMID: 23565499.  Invited Review.
  • Marino JS, Iler J, Dowling AR, Chua S, Bruning JC, Coppari R, Hill JW.  Adipocyte Dysfunction in a Mouse Model of Polycystic Ovary Syndrome (PCOS):  Evidence of Adipocyte Hypertrophy and Tissue-Specific Inflammation.  PLoS One 2012;7(10):e48643. PMID: 23119079
  • Marino JS, Peterson SJ, Li M, Vanella L, Sodhi K, Hill JW, Abraham NG.  ApoA-1 mimetic restores adiponectin expression and insulin sensitivity independent of changes in body weight in female obese mice.  Nutrition and Diabetes March 2012 2, e33. PMID: 23169576
  • Xu Y, Faulkner L, Hill JW.  Cross-talk between metabolism and reproduction:  The Role of POMC and SF-1 Neurons.  Frontiers in Systems and Translational Endocrinology 2012 January 4.  Invited Review. 
  • Patel PR, Ramakrishnan SK, Kaw MK, Raphael CK, Ghosh S, Marino JS, Heinrich G, Lee SJ, Bourey RE, Hill JW, Jung DY, Morgan DA, Kim JK, Rahmouni SK, Najjar SM.  Increased Metabolic Rate and Insulin Sensitivity in Male Mice Lacking the Carcinoembryonic Antigen-Related Cell Adhesion Molecule 2.  Diabetologia 2011 Dec 11. PMID: 22159884
  • Marino JS, Xu Y, Hill JW.  Central insulin and leptin-mediated autonomic control of glucose homeostasis.  Trends Endocrinol Metab. 2011 Apr 12. 
  • Xu Y, Hill JW (joint first author), Fukuda M, Gautron L, Sohn J, Kim K, Lee CE, Choi MJ, Lauzon D, Dhillon H, Lowell BB, Zigman JM, Zhao JJ, Elmquist JK. PI3K signalling in the ventromedial hypothalamus is required for normal energy homeostasis.  Cell Metabolism 2010 July 7;12(1), 88-95. PMID: 20620998
  • Hill JW, Elias CF, Fukuda M, Williams KW, Berglund ED, Holland WL, Cho Y, Chuang J, Xu Y, Choi M, Lauzon D, Lee CE, Coppari R, Richardson JA, Zigman JM, Chua S, Scherer PE, Lowell BB, Bruning JC, Elmquist JK.  Direct Insulin and Leptin Action on Pro-opiomelanocortin Neurons is Required for Normal Glucose Homeostasis and Fertility.  Cell Metabolism 2010 Apr 7;11(4):286-97. PMID: 20374961
  • Hill JW.  Gene Expression and the Control of Food Intake by Hypothalamic POMC/CART Neurons.  The Open Neuroendocrinology Journal 2010 3;21-27.  Invited Review
  • Hill JW, Yong X, Preitner F, Fukuda M, Cho Y, Luo J, Balthasar N, Coppari R, Cantley LC, Kahn B, Zhao JJ, Elmquist JK.  Phosphatidyl Inositol 3-Kinase Signaling in Hypothalamic Proopiomelanocortin Neurons Contributes to the Regulation of Glucose Homeostasis.  Endocrinology 2009 Nov;150(11):4874-82.
  • Fukuda M, Jones JE, Olson D, Hill J, Lee CE, Gautron L, Choi M, Zigman JM, Lowell BB, Elmquist JK.  Monitoring FoxO1 localization in chemically identified neurons. J Neurosci 2008 Dec 10; 28(50):13640-8. PMID: 19074037 
  • Hill JW, Elmquist JK, Elias CF.  Hypothalamic pathways linking energy balance and reproduction. Am J Physiol Endocrinol Metab. 2008 May; 294(5):E827-32. Epub 2008 Feb 19. 
  • Hill JW, Williams KW, Ye C, Luo J, Balthasar N, Coppari R, Cowley MA, Cantley LC, Lowell BB, Elmquist JK.  Acute effects of leptin require PI3K signaling in hypothalamic proopiomeanocortin neurons in mice.  J Clin Invest 2008 May 1; 118(5):1796-1805. 
  • Hill JW. Leptin, Insulin, AND PTEN: Divergent effects on hypothalamic neurons explained? Cell Science Reviews 2006; 3(2) 42-51. 
  • Hill JW, Urban JH, Xu M, Levine JE. Estrogen Induces Neuropeptide Y (NPY) Y1 Receptor Gene Expression and Responsiveness to NPY in Gonadotrope-Enriched Pituitary Cell Cultures.  Endocrinology 2004 May; 145(5):2283-90. 
  • Williams H, Connor DM, Hill JW. Testosterone decreases the potential for song plasticity in adult male zebra finches.  Horm Behav. 2003 Dec; 44(5):402-12. 
  • Hill JW, Levine JE.  Abnormal response of the neuropeptide Y-deficient mouse reproductive axis to food deprivation but not lactation. Endocrinology 2003 144(5):1780-6. 
  • Hill JW, Xu M, Levine JE.  Revisiting the reproductive functions of neuropeptide Y.  Current Opinion in Endocrinology, Diabetes, and Obesity 2002 9:203-214. 
  • Xu M, Hill JW, Levine JE.  Attenuation of luteinizing hormone surges in neuropeptide Y knockout mice.  Neuroendocrinology 2000 Nov; 72(5): 263-71
  • Xu M, Urban JH, Hill JW, Levine JE.  Regulation of hypothalamic neuropeptide Y Y1 receptor gene expression during the estrous cycle: role of progesterone receptors.  Endocrinology 2000 Sep; 141(9): 3319-27.
Last Updated: 3/22/15