Assistant Professor of Pharmacology
neuroimmunity, neuroinflammation, anxiety, depression, behavior, kynurenine, cytokines, glia
The immune system and the brain engage in an exquisite bidirectional communication network to orchestrate the host response to infection. This adaptive response includes physiological, metabolic and behavioral changes. The innate immune system is not only activated by pathogenic bacteria and viruses, but it often becomes chronically activated as a result of disease or even the normal aging process. When neuroimmune processes become dysregulated, there is a substantial increase in the risk of developing depressive disorders for individuals affected by these chronic inflammatory conditions. The neurobiological mechanisms and immune substrates underlying these immune-brain interactions are poorly understood.
My research is focused on understanding the biological basis of inflammation-related depressive disorders. To that end, we have developed clinically relevant mouse models of inflammation-induced depressive behavior. Using these models, we have identified a critical role for altered tryptophan metabolism in mediating depressive-like behavioral changes induced by peripheral immune activation. The essential amino acid, tryptophan is the biologic substrate for the formation of serotonin. However, during inflammatory conditions, an alternate tryptophan degrading pathway, called the kynurenine pathway, is activated. In macrophages and microglia, increased flux of tryptophan through this pathway produces a number of neuroactive kynurenine metabolites with the capacity to increase oxidative damage within the brain and to interact, both directly and indirectly, with the other neurotransmitter systems.
We are working to elucidate
Our goal is to provide new information and understanding of complex neuroimmune interactions that can be taken to the clinic and used to develop more effective therapeutic strategies to prevent or treat comorbid depression.
Accomplishments, Awards and Honors
Morrison Trust Award
Hogg Foundation for Mental Health Grant
Lectures, Posters and Presentations
'Neuroinflammatory and Metabolic Regulation of Behavior' - Waggoner Center for Alcohol and Addiction Research, University of Texas Austin - July 15, 2011
Laney Redus - Research Assistant
Allison Dugan - Graduate Student
Jennifer Parrott - Graduate Student
Juan Morales - Student Associate II