Mulholland Lab

The Mulholland Lab, led by Michael W. Mulholland, M.D., Ph.D. and Weizhen Zhang, M.D., Ph.D., is gaining new insights into energy homeostasis.

Current Research in the Mulholland Lab

The Mulholland Lab, led by Michael W. Mulholland, M.D., Ph.D. and Weizhen Zhang, M.D., Ph.D., conducts basic science investigations to understand the ways in which the area of the brain known as the hypothalamus controls appetite, energy balance and body weight. Driving our work has been the need for a greater understanding of the development of overweight and obesity in order to identify therapeutic targets and provide new treatment options to the patients for whom we care. Our laboratory has been continuously funded by the National Institutes of Health since 1986.

The Problem

Obesity affects more than one-third of the U.S. population and is becoming an international epidemic – with profound consequences. Affecting nearly every aspect of human health, obesity raises the risk of developing many diseases, including arthritis, cancer, cardiovascular disease, and diabetes and other metabolic diseases. Obesity also makes surgery more difficult, slows healing and increases the risk of complications.

The Approach

The urge to eat in order to gain and conserve energy is one of our most basic biological functions, and the body has many complex and redundant systems to achieve this. The efforts in our laboratory are aimed at understanding these intricate interactions. 

More specifically, we aim to unravel the molecular and cellular basis of how the hypothalamus regulates the expression of hormones and neurotransmitters essential to controlling appetite and food ingestion. We also investigate how these hormones and neurotransmitters influence the pancreas' role in digestion. To carry out our work, we use a range of biochemical and genetic approaches, including transgenic animal models and microarray analysis, to identify the protein complexes that activate and regulate the body's energy balance.

Contributions to Science

Our work has focused on clarifying the relationship between mammalian target of rapamycin (mTOR) and ghrelin, the “hunger hormone”. We have explored how energy balance is regulated by ghrelin and the hormone nesfatin-1 as well. Signaling from mTOR allows these hormones to control how lipids are metabolized and stored in the liver, which could lead to new treatments for nonalcoholic fatty liver disease.

In addition, we defined a system that controls energy balance over time through the regulation of the hypothalamic hormones proopiomelanocortin (POMC) and neuropeptide. Our findings clarifying the role of this system have advanced the understanding of the physiology of energy homeostasis.