Biomedical Graduate Studies

Description of Research Expertise

My expertise lies at the intersection between neuroscience and physiology. I study how internal physiological state is communicated and integrated by the brain. Disruption in how internal information is sensed and perceived has been implicated with impaired cognition, depression, metabolic disorders, autism, and anxiety. My lab has pioneered innovative approaches that combine peripheral and central manipulations and recordings which have revolutionized our ability to gain mechanistic understanding of the neural circuits involved in this novel research field. My lab focuses on the vagus nerve, as a gut-brain neural relay, to address questions about interoception in live animals. We have made numerous unexpected findings highlighting the extraordinary impact gut-brain signaling has on health and disease.

A key focus of my lab has been on treating obesity, a major global health problem. Despite decades of research, effective therapies for obesity remain elusive and the physical, emotional and economic costs of obesity continue to rise. The dogmatic belief that calories-in equals calories-out, has led to ineffective strategies that are over-reliant on exercise and reducing food intake. This view has stigmatized individuals with obesity as being lazy and lacking will power, while ignoring the complex pathophysiology of obesity that defends against weight loss by altering brain circuits associated with reward, learning, memory, and fullness. Current drugs targeting the central nervous system are plagued by aversive side effects. Thus, there is an urgent need to identify peripheral cellular and molecular targets for treating obesity.

The vagus nerve is a key component of the gut-brain axis that inhibits food intake, yet this neural pathway has been largely overlooked as a therapeutic target for treating chronic metabolic diseases. The textbook understanding is that the vagus nerve controls short-term food intake with little impact on long-term regulation of body weight. This dogmatic view is based on literature using vagotomy, a flawed technique which abolishes bidirectional vagal communication between abdominal organs and the brain. The lack of organ specificity, and confounds caused by damaging motor branches of the vagus nerve that control organ function, makes it difficult to interpret the outcomes from these experiments. My lab is developing new tools to study precise populations of vagal sensory neurons that selectively innervate the gut. I pioneered the application of molecular and genetic tools to deconstruct the sensory vagus nerve into cellular components based on genetic markers, projection patterns, and functional responses. I subsequently adapted viral technology for connectivity mapping, in vivo imaging, cell ablation and control of neural activity to study the role of these previously intractable neurons in the control of eating. Using these tools, we have identified previously unsuspected roles of the sensory vagus nerve in many aspects of higher order feeding behavior, including reward, memory, anxiety, and fullness.