Director: Timothy Moran, Ph.D.
Our overall research program is aimed at identifying the roles of various neural signaling pathways in the controls of food intake and body weight. The current research takes a number of approaches. The first involves the identification of the neural representation of meal-related satiety signals. Multiple feedback signaling pathways are activated by food ingestion and the gastrointestinal presence of digestion products. We are examining how signals from multiple sites and stimulus modalities are integrated within specific brain nuclei and, in an effort to model eating disorders, how alterations in feeding patterns can influence these neural representations.
The second approach involves the identification of interactions between peripheral, within-meal, satiety signals and hypothalamic peptide systems involved in overall energy balance. We are currently examining how the activity of hypothalamic leptin, NPY, CCK, CFR, CART and melanocortin systems interact with ascending satiety pathways to alter meal size. We are also investigating how alteration in cellular energy availability and production are transduced into changes in food intake and body weight. These experiments focus on the de novo fatty acid synthesis pathway in critical hypothalamic sites and take advantage of a novel group of chemicals that inhibit the production of fatty acids and/or stimulate fatty acid oxidation. We are examining how exercise not only increases energy expenditure but also reduces food intake. These experiments focus on the regulation of peptide gene expression in hypothalamic systems involved in energy balance.
Finally, we are examining how gestational factors can bias metabolic programming to contribute to altered feeding and obesity. Experiments are conducted at multiple levels and employ behavioral, physiological and molecular in vivo and in vitro paradigms.
LAB MEMBERS
Ellen E. Ladenhiem, Ph.D., Associate Professor laden@jhmi.edu 410-614-1750 My research interests involve delineating the role of bombesin-like peptides in the control of food intake. Bombesin-like peptides are found in the mammalian gastrointestinal tract and central nervous system and have been shown to suppress food intake when administered to a variety of mammalian species, including humans. The overall objective of this research program is to determine the neural pathways and mechanisms utilized by mammalian BN-like peptides to inhibit feeding and examine how these peptides interact with other peptides that participate in energy balance and body weight regulation. Link to PubMed publications for Ladenhiem, EE |  |
 | Sheng Bi, M.D., Assistant Professor sbi@jhmi.edu 410-502-4789 The goal of my research is to understand how hypothalamic peptide signaling affects food intake and energy balance by using various techniques such as in situ hybridization, immunohistochemistry, central peptide administration and recombinant adeno-associated virus system for delivering genes or RNA interference with short interfering RNA (siRNA). In addition, we do in vitro studies to understand the regulation of energy metabolism at molecular biological levels using techniques such as cell culture, gene transfection, Western blotting, Northern blotting and real time RT-PCR. Link to PubMed publications for Bi, S |
 | Nicholas T. Bello, Ph.D., Postdoctoral Fellow ntbello@jhmi.edu 410-955-2996 Binge eating is a common feature presented by some patients with eating disorders or obesity. The focus of my research is to investigate the neural mechanisms that are involved in the initiation and maintenance of binge eating. My particular interest is in the caudal brainstem, since it receives and integrates information related to meal states. Moreover, the nucleus of the solitary tract has extensive reciprocal projections to forebrain areas that play a large role in long term body weight regulation and the establishment of food choices. I am currently using anatomical, molecular, and behavioral techniques in rodents to analyze the neural alterations that underlie this aberrant feeding behavior. Link to PubMed publications for Bello, NT |
Kellie L. K. Tamashiro, Ph.D. ktamashiro@jhmi.edu 410-955-2996 Overweight and obesity is a growing public health problem worldwide, particularly among children. My current studies examine how environmental manipulations during development, specifically the intrauterine and early postnatal environments, influence the metabolic phenotype of the offspring. We are using a rat model to study the short- and long-term behavioral, neuroendocrine, and metabolic consequences of prenatal stress and changes in maternal nutrition. Link to PubMed publications for Tamashiro, KL |  |
 | Su Gao, Graduate Student sgao@jhmi.edu 410-955-2344 I study the molecular mechanisms underlying the hypothalamic actions of leptin, an anorexigenic hormone. Specifically, I am interested in how the pathway involving AMP kinase (AMPK), Acetyl CoA Carboxylase (ACC) and Malonyl CoA (the product of ACC catalyzed reaction) mediate the anorectic effects of leptin. The methodology involves biochemical, pharmacological and genetic approaches and I use both rodent models and cell culture systems to address the questions. |