Overweight and obesity are important surgical problems. As major contributing factors to the pathogenesis of many disease processes treated by the surgeon, overweight and obesity have a profound impact on present day surgical practice. Research in the Dr. Mulholland's lab has been to study the molecular basis of overweight and obesity. We have approached our study by examining the two most important components of the autonomic neuronal circuitry involving in the control of body weight: the dorsal vagal complex and the hypothalamus. Because of the key role of the dorsal vagal complex in the control of food intake by regulating gastrointestinal functions ranging from motility to secretion, we investigate the neuronal control mechanism by a combination of molecular and biochemical approaches. We have found that a range of neuronal feeding peptides involve in the control of pancreatic enzyme secretion by altering neuronal functions of the dorsal vagal complex. We are currently examining the mechanism of this regulation by using multiple approaches including transgenic mice, gene silencing, in vitro neuronal culture and in vivo animal models.
The second project examines the arcuate nucleus hypothalamic genes involved in energy homeostasis. We have identified ankyrin repeat and SOCS box containing protein 4 (Asb-4) as a very promising investigative target. Asb-4 is an important intracellular regulatory protein in CNS energy homeostatic circuits that is highly regulated in hypothalamic neurons. Using the advanced molecular techniques including gene knock-in and conditioned knock-out, we are currently exploring the physiological role of Asb-4 on the energy homeostasis.
In summary, we are studying overweight and obesity which have significant roles in determining the types of diseases treated by surgeons and also have substantial impact on postoperative morbidity and mortality. Surgical treatment, in the form of gastric bypass, has become accepted therapy for morbid obesity. The long-term objective of our research has been to understand the physiology of energy balance. By doing so, we hope to provide new insights for the treatment for obesity that ameliorate the effects this condition has in surgery, and ultimately, that eliminate the need for operative treatment.

Key Words:
Food intake, body weight, hormone, hormone regulation /control mechanism, obesity, pathologic process, clinical research, microarray technology, polymerase chain reaction, gene knock-out, transgenic mice