Our Research Interests

Great strides have been made recently in determining the endocrine mechanisms and neuroanatomical pathways that are involved in the development of obesity. One such mechanism involves ghrelin, a hormone that stimulates food intake in animals and whose levels are raised in association with hunger, diet-induced weight loss and certain forms of obesity in humans. Ghrelin also has several other functions, including modulation of insulin release and roles in gastrointestinal motility, gastric acid secretion, and growth hormone release, among others. However, important information regarding exactly how ghrelin influences food intake, body weight and pancreatic islet function or how ghrelin biosynthesis and release are controlled remain to be determined.

My past studies, which were performed in the laboratory of Joel K. Elmquist and with the help of numerous colleagues and collaborators from Dr. Elmquist's and Bradford B. Lowell's laboratories at Beth Israel Deaconess Medical Center in Boston, MA and elsewhere, included detailed histochemical analyses of the CNS distribution of ghrelin's receptor and the chemical phenotypes of ghrelin-responsive neurons, examination of the role of the ghrelin receptor in the development of obesity, and examination of the role of the ventromedial hypothalamic nucleus (VMH) in body weight homeostasis.

Our current research focuses on gaining a better understanding of ghrelin’s roles in the regulation of feeding behavior and body weight, the development of diet-induced obesity and the maintenance of glucose homeostasis. Of particular interest are the roles of ghrelin in reward-seeking behaviors, such as those resulting in increased food intake and the acquisition of addictive substances, and in other hedonic properties of eating.  We also have ongoing studies to further clarify the role we have recently described for ghrelin in reducing depression and anxiety.  We are using transgenic and neuroanatomical approaches to determine the central and peripheral expression patterns of ghrelin and ghrelin’s receptor, to characterize the chemical phenotypes of ghrelin-responsive neurons, and to determine whether these ghrelin-responsive neurons innervate key autonomic, neuroendocrine and behavioral control sites in the brain.

We also have generated a conditional knock-in animal model to determine if intact, ghrelin-engaged neuronal circuitry is required for normal body weight homeostasis and the maintenance of glucose tolerance and to determine the important CNS and peripheral sites of direct ghrelin action. Sites of interest include the ventral tegmental area, arcuate nucleus and caudal brainstem, among others.

We are using similar approaches to characterize the circulating compounds and neurotransmitters leading to ghrelin release, to characterize the enzyme responsible for ghrelin’s unique post-translational modification, and to investigate further the role of ghrelin in the profound changes associated with various forms of bariatric surgery.

The ultimate goal of these studies is to enable the design of novel therapeutics to treat and/or prevent obesity, diabetes, substance abuse, depression, anorexia nervosa, Prader-Willi Syndrome and other conditions.