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 peptide hormone whose circulating levels are influenced mainly by the release of ghrelin from specific endocrine cells lining the stomach and intestine.  Ghrelin is of particular interest to obesity researchers because it stimulates food intake and its 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.  As mentioned below, my group recently also demonstrated that ghrelin also influences behaviors associated with mood and anxiety.  However, important information regarding exactly how ghrelin influences these behaviors, food intake, body weight and pancreatic islet function or how ghrelin biosynthesis and release are controlled remain to be determined.

My major contributions to the ghrelin literature have included a detailed study of the distribution of ghrelin receptors throughout the rat and mouse brains, a study with a novel ghrelin receptor-null mouse line in which we demonstrated the requirement of intact ghrelin signaling pathways for the development of diet-induced obesity, and a study describing new antidepressant and anxiety-lowering roles for ghrelin – especially following chronic stress.  I have also worked on examining the role of the ventromedial hypothalamic nucleus (VMH) in body weight homeostasis.  These studies were performed while I was a member of Joel Elmquist's lab in Boston and more recently in my own lab, through collaborations with Dr. Elmquist and Drs. Michael Lutter and Eric Nestler in Dallas.  

My current research focuses on gaining a better understanding of ghrelin’s roles in the regulation of body weight, the regulation of hedonic/pleasurable aspects of eating (food reward), the regulation of mood and anxiety, and the maintenance of glucose homeostasis.  These studies involve the use of various neuroanatomical approaches as well as unique transgenic mouse models in which we can selectively restrict or selectively disable ghrelin receptor expression from specific brain sites, specific neuronal subtypes or specific peripheral cell types.  Sites of interest include various hypothalamic nuclei, midbrain dopaminergic reward circuits, the caudal brainstem and the pancreatic islets of Langerhans.  

Another main interest of my lab involves investigations of ghrelin cell physiology.  In particular, I am interested in learning the molecular basis for ghrelin biosynthesis and ghrelin release.  These studies largely make use of a novel transgenic mouse model in which green fluorescent protein is expressed under the control of the ghrelin promoter.  

I am also interested in further elucidating the changes in various aspects of physiology induced by different types of bariatric (weight loss) surgery.  My collaborators and I aim to link surgery-induced changes in hedonic aspects of eating, mood, cognitive function, and body composition to alterations in brain activity and hormonal profiles.  

As mentioned, many of my team’s studies rely on novel, genetically-engineered mouse models, and I currently have several others under development to further explore the lab’s interests.  The ultimate goal of these studies is to enable the design of therapeutics to treat and/or prevent obesity, cachexia, anorexia nervosa, depression, diabetes, substance abuse, and other conditions.