Department of Physiology and Pharmacology

Jennifer W. Hill, Ph.D.

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, Department of Physiology & Pharmacology and Department of Obstetrics and Gynecology (joint appointment), 2009
• University of Toledo College of Medicine, Toledo OH.  Associate Professor (tenured), Department of Physiology & Pharmacology and Department of Obstetrics and Gynecology (joint appointment), 2016
• University of Toledo, Toledo OH.  Associate Director of Basic Research, The Center for Diabetes and Endocrine Research (CeDER), 2019
• University of Toledo College of Medicine, Toledo OH.  Full Professor (tenured), Department of Physiology & Pharmacology and Department of Obstetrics and Gynecology (joint appointment), 2023

Honors and Awards

• Taylor and Francis Top Author Recognition, 2022
• NIH Research Project Grant R01 HD104418, May 2022
• Dean’s Award for Research Excellence, U Toledo College of Medicine and Life Sciences, 2021
• University of Toledo President’s Award for Excellence in Grantsmanship, 2019      
• NICHD strategic planning working group appointee, 2018        
• Physiology Faculty Mentor Student's Choice Award, 2017
• NICHD nominee for the Presidential Early Career Award for Scientists and Engineers (PCASE), 2016
• 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

• American Diabetes Association, Member
• American Physiological Society Member, Endocrinology & Metabolism and CNS subsections
• Endocrine Society, Member of the Committee on Diversity and Inclusion (2017-2020)
• Pan American Neuroendocrine Society, Member
• Society for Behavioral Neuroendocrinology, Chair of the Professional Development Committee
• Society for the Study of Reproduction (SSR), Future Meetings Committee Member (2019-2020)
• Women in Endocrinology, Chair of the Awards Committee
• NIH Integrative Physiology of Obesity and Diabetes Study Section [IPOD/POMD], Member 2017-2021
• NSF BIO/IOS Neural Systems Cluster Review Panel, ad hoc reviewer
• NIH Integrative and Clinical Endocrinology and Reproduction (ICER) Study Section, ad hoc reviewer
• NIH SCCPIR U54 Review Panel, MDCN Study Section R15 Panel, MPMOD Consortium Review Panel, ad hoc reviewer
• NIDDK Diabetic Complications Consortium P&F Reviewer
• UK Biotechnology and Biological Sciences Research Council Reviewer (ad hoc)
• Swiss National Science Foundation review panel
• Health Research Council of New Zealand fellowship review panel
• Ad-hoc Journal Reviewer:  Cell Metabolism, Endocrinology, JCI Insights, Molecular Metabolism, Obesity, Science, Scientific Reports, The
• FASEB Journal, The Journal of Neuroscience

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

• Semple EA, Harberson MT, Xu B, Rashleigh R, Cartwright TL, Braun JJ, Custer AC, Liu C, Hill JW. Melanocortin 4 receptor signaling in Sim1 neurons permits sexual receptivity in female mice. Front Endocrinol (Lausanne). 2023 Mar 24;14:983670. doi: 10.3389/fendo.2023.983670. eCollection 2023. PMID: 37033219
• Shermel B. Sherman, Mitchell Harberson, Rebecca Rashleigh, Niraj Gupta, and Riley Powers, Ramya Talla, Ashima Thusu, and Jennifer W. Hill. Spexin modulates molecular thermogenic profile of adipose tissue and thermoregulatory behaviors in female C57BL/6 mice. Hormones and Behavior. 2022 14-July Vol. 143
• “Current Genetic Techniques Available for Investigating Feeding Behavior and the Control of Energy Balance” by Mitchell T. Harberson and Jennifer W. Hill. Ch 7 in Neuron Signaling in Metabolic Regulation by Qingchun Tong (Editor) Taylor & Francis, June 8, 2021 (Methods in Signal Transduction Series), p121-141
• Harberson MT, Hill JW. Bremelanotide. In: Offermanns S, Rosenthal W, editors. Encyclopedia of Molecular Pharmacology. Cham: Springer International Publishing; November 14, 2021. p. 1-6. ISBN 978-3-030-57400-0 eBook ISBN 978-3-030-57401-7
• Rachel M Golonka, Johnathan K Cooper, Rochell Issa, Pratyush P Devarasetty, Veda Gokula, Joshua Busken, Jasenka Zubcevic, Jennifer W Hill, Matam Vijay-Kumar, Bindu Menon, Bina Joe. Impact of Nutritional Epigenetics in Essential Hypertension: Targeting microRNAs in the Gut-Liver Axis. Current Hypertension Reports, 23(5): 28. May 7 2021 (invited review)
• Maggie Evans, Jennifer W. Hill, Gregory Anderson. The role of insulin in the neuroendocrine control of reproduction.  Journal of Neuroendocrinology. 2021 Feb 1;33(4):e12930.
• Kathryn B.Smedlund, Jennifer W.Hill. The role of non-neuronal cells in hypogonadotropic hypogonadism. Molecular and Cellular Endocrinology Page 110996 Published 1 December 2020.
• Iyad H Manaserh, Emily Maly, Marziyeh Jahromi, Lakshmikanth Chikkamenahalli, Joshua Park and Jennifer Hill. Insulin sensing by astrocytes is critical for normal thermogenesis and body temperature regulation. JOURNAL OF ENDOCRINOLOGY (IF 4.041) Volume 247: Issue 1 Page 39-52 Published Oct 2020
• Chakraborty, Saroj ; Mandal, Juthika ; Yang, Tao ; Cheng, Xi ; Yeo, Ji-Youn ; McCarthy, Cameron G. ; Wenceslau, Camilla F. ; Koch, Lauren G. ; Hill, Jennifer W. ; Vijay-Kumar, Matam ; Joe, Bina. Metabolites and Hypertension: Insights into Hypertension as a Metabolic Disorder 2019 Harriet Dustan Award HYPERTENSION (IF 7.713) Volume 75 Issue 6 Page 1386-1396 Originally published 27 Apr 2020
• Wang, Mengjie ; Zhang, Youjie ; Miller, David ; Rehman, Naveen O. ; Cheng, Xi ; Yeo, Ji-Youn ; Joe, Bina ; Hill, Jennifer W.  Microbial Reconstitution Reverses Early Female Puberty Induced by Maternal High-fat Diet During Lactation ENDOCRINOLOGY (IF 3.934) Volume 161 Issue 2: bqz041Published Jan 8 2020 PMC7035910
• Ghadieh HE, Russo L, Muturi HT, Ghanem SS, Manaserh IH, Noh HL, Suk S, Kim JK, Hill JW, Najjar SM. Hyperinsulinemia drives hepatic insulin resistance in male mice with liver-specific Ceacam1 deletion independently of lipolysis. Metabolism. 2019 Apr;93:33-43. PubMed PMID: 30664851
• Manaserh IH, Chikkamenahalli L, Ravi S, Dube PR, Park JJ, Hill JW. Ablating astrocyte insulin receptors leads to delayed puberty and hypogonadism in mice. PLoS Biol. 2019 Mar;17(3):e3000189. PMID: 30893295; PubMed Central PMCID: PMC6443191.
• Semple E, Shalabi F, Hill JW. Oxytocin Neurons Enable Melanocortin Regulation of Male Sexual Function in Mice. Mol Neurobiol. 2019 Feb 12. PMID: 30756300.
• Semple E, Hill JW. Sim1 neurons are sufficient for MC4R-mediated sexual function in male mice. Endocrinology. 2018 Jan 1;159(1):439-449. PMID: 29059347 See also Editorial Comment J Urol. 2018 Nov;200(5):948. PMID: 30360347
• Hill JW and Elias CF. Neuroanatomical Framework of the Metabolic Control of Reproduction. Physiological Reviews (Invited Review) Physiol Rev. 2018 Oct 1;98(4):2349-2380. PMID: 30109817
• Jahromi MS, Hill JW, Tehrani FR, Zadeh-Vakili A. Hypomethylation of specific CpG sites in the promoter region of steroidogeneic genes (GATA6 and StAR) in prenatally androgenized rats. Life Sciences, 2018 Aug 15;207:105-109.
• Shermel B Sherman SB, Sarsour N, Jahromi MS, Schroering A, Mell B, Joe B, Hill JW. Prenatal Androgen Exposure Causes Hypertension and Gut Microbiota Dysbiosis. Gut Microbes. 2018 Feb 22:1-45. PMID: 29469650 2022 TF Top Author paper: among the most highly cited in Gut Microbes in the last five years
• “Obesity and Stress: The Melanocortin Connection” by Sara Singhal and Jennifer W. Hill, Ch 11 in Textbook of Energy Balance, Neuropeptide Hormones, and Neuroendocrine Function, Eduardo Nillni, Editor. Springer Press, 2018
• 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.