Matthew R Hayes
Perelman School of Medicine, University of Pennsylvania
125 South 31st Street
Philadelphia, PA 19104
Philadelphia, PA 19104
B.S. (Biological Sciences)
Clemson University, 2002.
Ph.D. (Nutritional Sciences)
The Pennsylvania State University, 2006.
Postdoctoral Fellow, University of Pennsylvania, Department of Psychology, 2006-2010.
Description of Research ExpertiseThe overarching goal of the Hayes lab is to identify and characterize the neural signaling pathways controlling for food intake and body weight regulation in an effort to treat obesity and associated co-morbidities. To this end, our research examines the behavioral, intracellular, neuronal and endocrine mechanisms governing energy balance and how these processes are dysregulated in obesity.
A major theme of research in our lab focuses on the neuropeptide glucagon-like peptide-1 (GLP-1) and its role in regulating energy balance through action in the periphery on the vagus nerve (cranial nerve X), as well as the central nervous system (CNS). The potential for GLP-1 receptor agonists to be used as a pharmacological treatment for obesity has been highlighted in a number of recent publications. For this to become a reality, however, will require a deepened understanding of the behavioral, neuronal, and physiological mechanisms by which the peripheral and central GLP-1 systems control for food intake and body weight regulation.
Reward / Motivated Feeding: Why We Override Our Satiation Signals.
It is clear that the excessive food intake, especially of palatable foods, that contributes to human obesity is not driven by metabolic need alone. While our lab investigates the importance of neuropeptide signaling on vagal afferents and in hindbrain and hypothalamic nuclei for the homeostatic control of food intake, it is also critical to examine and better define the neural basis of non-homeostatic controls of food intake.
Ongoing extensive investigations in our lab are examining the neuroendocrine systems that connect within-meal inhibitory feedback from gastrointestinal satiation signals to nuclei in the mesolimbic reward system (MRS), including the ventral tegmental area and nucleus accumbens. Activation of the MRS by these neuroendocrine systems is postulated to decrease motivation to continue feeding, leading to meal termination. Thus, current projects are investigating the behavioral, molecular, neuronal and physiological mechanisms by which energy balance-relevant neuropeptides (such as glucagon-like peptide-1, leptin and amylin) are modulating the non-homeostatic controls of feeding mediated by nuclei in the MRS.
Integrative Systems Neuroscience of Energy Balance
While the CNS control of energy balance involves redundant and anatomically distributed processing across the CNS, a few nuclei, such as the nucleus tractus solitarius (NTS) of the hindbrain, stand out as essential for the processing and integration of a variety of ascending and descending pathways controlling for food intake and energy balance. It is also very clear that more progress could be made in the treatment of obesity if research focused attention on these specific CNS nuclei that serve as hubs for the neural control of energy balance. Thus, our lab explores the intracellular mechanisms by which multiple neurochemical systems interact and synergize at the level of the NTS to control for energy balance.
From Hunger to Nausea: Points on the same spectrum of ingestive behavior.
More than 1.6 million cases of cancer are diagnosed yearly in the United States. The toll on the patient can be life-threatening, and unfortunately the pharmacological- and radiation-treatment options for cancer are commonly accompanied by a host of undesirable side effects (pain, diarrhea, anorexia, nausea, vomiting). The severity of these side effects can cause cancer patients to delay or refuse chemotherapy, in turn leading to increased patient morbidity and mortality. With approximately 80% of chemotherapy patients experiencing chemotherapy-induced nausea and vomiting, there is an urgent need to develop more effective anti-emetic and anti-nausea treatments to improve the quality of life for cancer patients undergoing chemotherapy and/or radiation therapy.
Similar to the widely accepted view of nausea being a major side effect for cancer treatment, nausea and/or vomiting are the primary adverse events (i.e. side effects) reported in many patients receiving pharmacotherapy for Type 2 Diabetes Mellitus (T2DM). Indeed, ~20-50% of T2DM patients maintained on the GLP-1R agonists (liraglutide and exendin-4) report nausea/vomiting, and yet there is very little investigation of the mechanisms mediating the nausea/malaise and virtually no understanding of the significance of nausea/malaise in relation to GLP-1 receptor-mediated suppression of food intake.
Although rodents lack the physiology needed to vomit, behavioral paradigms such as pica (ingestion of non-nutritive substances) and conditioned taste avoidance (CTA) are used commonly in both rats and mice as models for the study of malaise and nausea. Our lab utilizes these well-established rat models of malaise to determine the neural pathways and physiological mechanisms responsible for mediating the nausea/malaise induced by GLP-1 receptor ligands and chemotherapy drugs, as well as to determine whether the nausea/malaise is correlated or causal for the intake-inhibitory effects of GLP-1 receptor-targeting pharmaceuticals.
Selected PublicationsDe Jonghe Bart C, Hayes Matthew R, Kanoski Scott E, Zimmer Derek J, Grill Harvey J, Bence Kendra K: Food intake reductions and increases in energetic responses by hindbrain leptin and melanotan II are enhanced in mice with POMC-specific PTP1B deficiency. American journal of physiology. Endocrinology and metabolism Jul 2012.
Kanoski Scott E, Zhao Shiru, Guarnieri Douglas J, Dileone Ralph J, Yan Jianqun, De Jonghe Bart C, Bence Kendra K, Hayes Matthew R, Grill Harvey J: Endogenous leptin receptor signaling in the medial nucleus tractus solitarius affects meal size and potentiates intestinal satiation signals. American journal of physiology. Endocrinology and metabolism Jun 2012.
Hayes Matthew R: Neuronal and intracellular signaling pathways mediating GLP-1 energy balance and glycemic effects. Physiology & behavior 106(3): 413-6, Jun 2012.
Hopkins Thomas J, Rupprecht Laura E, Hayes Matthew R, Blendy Julie A, Schmidt Heath D: Galantamine, an Acetylcholinesterase Inhibitor and Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors, Attenuates Nicotine Taking and Seeking in Rats. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Jun 2012.
Spaeth Andrea M, Kanoski Scott E, Hayes Matthew R, Grill Harvey J: TrkB receptor signaling in the nucleus tractus solitarius mediates the food intake-suppressive effects of hindbrain BDNF and leptin. American journal of physiology. Endocrinology and metabolism 302(10): E1252-60, May 2012.
Kanoski Scott E, Rupprecht Laura E, Fortin Samantha M, De Jonghe Bart C, Hayes Matthew R: The role of nausea in food intake and body weight suppression by peripheral GLP-1 receptor agonists, exendin-4 and liraglutide. Neuropharmacology 62(5-6): 1916-27, Apr 2012.
Alhadeff Amber L, Rupprecht Laura E, Hayes Matthew R: GLP-1 neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake. Endocrinology 153(2): 647-58, Feb 2012.
Zhao S, Kanoski S E, Yan J, Grill H J, Hayes M R: Hindbrain leptin and glucagon-like-peptide-1 receptor signaling interact to suppress food intake in an additive manner. International journal of obesity (2005) Jan 2012.
Faulconbridge Lucy F, Hayes Matthew R: Regulation of energy balance and body weight by the brain: a distributed system prone to disruption. The Psychiatric clinics of North America 34(4): 733-45, Dec 2011.
McKay Naomi J, Kanoski Scott E, Hayes Matthew R, Daniels Derek: Glucagon-like peptide-1 receptor agonists suppress water intake independent of effects on food intake. American journal of physiology. Regulatory, integrative and comparative physiology 301(6): R1755-64, Dec 2011.