Department of Physiology and Pharmacology

Jennifer W. Hill, Ph.D.

Associate Professor
Phone: 419.383.6137
Fax: 419.383.2871
Email: JenniferW.Hill@utoledo.edu

Curriculum Vitae

Complete list of publications

 

 

Areas of Expertise

The neural and endocrine regulation of behavior related to reproduction and food intake, the hypothalamic control of energy balance, leptin and insulin intracellular signaling, central effects of sex steroids, the control of GnRH release, Kiss1 neuron function, polycystic ovary syndrome, and the integrated physiology underlying obesity, diabetes, and reproductive disorders.

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
• University of Toledo College of Medicine, Toledo, OH.  Assistant Professor, Center for Diabetes and Endocrine Research (CeDER), Department of Physiology & Pharmacology, University of Toledo, College of Medicine, 2009
• University of Toledo College of Medicine, Toledo OH.  Associate Professor (tenured), Center for Diabetes and Endocrine Research (CeDER), Department of Physiology & Pharmacology, 2016

Honors and Awards

• NICHD nominee for the Presidential Early Career Award for Scientists and Engineers (PCASE), 2016
• Physiology Faculty Mentor Student's Choice Award, 2017
• UT Biomedical Research Innovation Award, 2016
• NIH Research Project Grant R01 HD081792, April 2015
• 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

• Standing member of NIH Integrative Physiology of Obesity and Diabetes Study Section [IPOD]
• Society for the Study of Reproduction, Member
• Ad hoc reviewer for NIH Integrative and Clinical Endocrinology and Reproduction (ICER) Study Section
• 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
• Sigma Xi, 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 necessary to maintain fertility. As many as 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, and IGF-1 are perceived directly or indirectly by GnRH neurons of the hypothalamus and maintain reproductive health.  The cornerstone of my laboratory’s efforts is timed, targeted genetic manipulation to alter neuronal activity or gene expression. Combined with anatomical, electrophysiological, and physiological techniques, this approach offers a powerful tool for investigating the hypothalamic control of metabolism and fertility and identifying targets for medical treatment.

 Publications

• Hill JW and Faulkner LD. The Role of the Melanocortin System in Metabolic Disease: New Developments and Advances. (Invited Review) Neuroendocrinology  104(4):330-346 2017
• Jahromi MS, Tehrani FR, Hill JW, Noroozzadeh M, Zarkesh M, Ghasemi A; Zadeh-Vakili A. Alteration in follistatin gene expression detected in prenatally androgenized rats. Gynecological Endocrinology Feb 26:1-5 2017. PMID: 28277126
• Garcia-Galiano D, Borges BC, Donato J Jr, Allen SJ, Bellefontaine N, Wang M, Zhao JJ, Kozloff KM, Hill JW, Elias CF. PI3Kα inactivation in leptin receptor cells increases leptin sensitivity but disrupts growth and reproduction. JCI Insight. 2017 Dec 7;2(23). pii: 96728. PubMed PMID: 29212950.
• Wang M, Zhang Y, Lan D, Hill JW. The Efficacy of GnRHa Alone or in Combination with rhGH for the Treatment of Children with Central Precocious Puberty: A Systematic Review and Meta-Analysis. Scientific Reports 2016 Apr 13;6:24259. PMID: 27072597
• Heinrich G, Russo L, Castaneda T, Pfeiffer V, Ghadieh H, Ghanem S, Wu J, Faulkner L, Ergun S, Hill J, and Najjar S. Leptin Resistance Contributes to Obesity in Mice with Null Mutation of Carcinoembryonic Antigen Cell Adhesion Molecule 1. Journal of Biological Chemistry Volume: 291   Issue: 21   Pages: 11124-11132   MAY 20 2016
• Qiu X, Dao H, Heston A, Garcia KM, Sangal A, Wang M, Dowling AR, Faulkner L, Molitor SC, Elias CF, Hill JW.  Insulin and leptin signaling interact in the Kiss1 neuron during the peripubertal period.  PLOS One 2015 10(5):e0121974.  PMID:  25946091
• Faulkner LD, Dowling AR, Stuart RC, Nillni EA, Hill JW.  Reduced melanocortin production causes sexual dysfunction in male mice with POMC neuronal insulin and leptin insensitivity.  Endocrinology 2015 156(4):1372-1385.  PMID: 25590244
• 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 289:(25):17885-17894.  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.