Research

Research Projects

We use calcium imaging, electrophysiology, genetic models, and state-of-the-art neuroscience tools to evaluate the specific contributions of defined neural populations to the regulation of body weight, glucose metabolism and motivated behaviors such as food intake. We seek to uncover how disruptions in these physiologic systems lead to or are altered by disease processes, such as obesity, dysregulated feeding, anxiety and substance use disorders. Specific research interests include:

Gut-brain communication and satiety signaling

Satiety signaling from the hindbrain is an important aspect of the complex regulation of feeding behavior and energy balance in the body. The hindbrain, particularly the brainstem, is involved in receiving and processing signals related to nutrient intake and energy status. This project examines the regulation and function of specific neuronal populations within the nucleus of the solidary tract (NTS) and area postrema (AP).

We study how interoceptive signals from the gut and circulating peripheral factors that convey nutrient status, such as hormones, and incretin peptides (ex glucagon-like peptide, GLP-1, and glucose dependent insulinotropic polypeptide, GIP) converge to regulate AP/NTS neuronal activity to regulate feeding behavior.

We further explore how satiety signals from the NTS/AP are integrated with signals from higher brain regions, including the thalamus and hypothalamus, crucial regulators of appetite, and regions that drive hedonic food intake.

We are pursing how the hindbrain's satiety signals adapt to changes in diet, metabolic state, and chronic conditions like obesity. Understanding the plasticity of these signaling pathways can provide insights into strategies for managing conditions related to energy imbalance.

Alongside these studies is the examination of the detailed mechanisms through which these hindbrain circuits contribute to the stress response and substance use disorders.

Orexin-regulated neural circuitry

Orexin (OX), also known as hypocretin, refers to a group of neuropeptides, OX-A and OX-B, derived from a common precursor, produced by neurons in the hypothalamus. OX-producing neurons project to numerous brain regions where OX peptides act at two receptor subtypes 1 and 2 (OX1R and OX2R) to regulate various physiological processes.

The functions associated with orexin include the regulation of sleep-wake cycles, arousal, appetite, regulation of energy homeostasis, reward pathways, and stress responses. The discovery of orexin and its functions has opened avenues for research into understanding and treating sleep disorders, obesity, and other conditions related to neural regulation. Pharmaceuticals targeting orexin receptors are being explored for their potential in managing sleep disorders and other neurological and psychiatric conditions.

We have developed unique genetic mouse models to identify and selectively modulate the activity of OX1R or OX2R- expressing neurons. This project examines how specific OXR-expressing neurons and OX signaling in regions such as the thalamus impact feeding behavior, reward seeking, and the stress response.

We also study how OX-regulated circuits in the retrosplenial cortex impact spatial memory processing under normal physiologic conditions and during the progression of Alzheimer's disease.