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.
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.
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.
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.
Zachary Cordner, M.D.-Ph.D.
Broadly, my research interests focus on modeling the effects of genes and the environment on risk for psychiatric disorders. In the lab, I use mouse and rat models to understand how exposure to various stressors and genetic predispositions might impact the brain and behavior. Ongoing projects are focused on determining 1.) why chronic stress seems to increase the risk for cognitive impairment and Alzheimer’s disease, 2.) how early life stressors affect an individuals risk for mental illness later in life, and 3.) using social stress to model mood and anxiety disorders in order develop new treatment strategies and biomarkers for identifying at-risk individuals.
Matthew Hurley, Ph.D.
Seva Khambadkone, M.D.-Ph.D. student
My research interests focus on environmental determinants of brain and behavior. I'm particularly interested in identifying environmental factors that affect low-resource communities, such as poor diet, how such factors may influence neurodevelopment and neuropsychiatric risk, and how to design preventative and therapeutic interventions. In the lab, I use behavioral and molecular biology techniques to study rodent models, with relevance to broader clinical and public health translatability.
Kimberly R. Smith, Ph.D.
Overall, I’m interested in understanding the neurobiological mechanisms underlying eating-related disorders and determining how factors such as taste and food choice influence patient and treatment outcomes. I’m currently conducting my postdoctoral fellowship in clinical research where I am applying sophisticated neuroimaging acquisition and analysis techniques with rigorous behavioral assessments to identify mechanisms of disease and therapeutic targets to improve patient and treatment outcomes. I have a solid foundation in preclinical neurobiological studies assessing the genetic and behavioral factors that influence food intake using psychophysical methods in rodent models from my predoctoral training in neuroscience. During my postdoctoral fellowship I transitioned to translational clinical research to develop a skillset in the conduct of clinical research and magnetic resonance imaging methods and apply my basic research training to inform the design of clinically-relevant studies in eating-related disorders across the age (adolescents and adults) and weight spectrum (e.g. in individuals with obesity and those with anorexia nervosa).