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My major research interests explore structural, functional and molecular biological principles underlying stress integration, with an emphasis on delineating mechanisms linking stress with mental illness and cognitive disorders. The organismal ‘stress response’ represents an integrated physiological process whose primary goal is to redistribute energy to meet a real or perceived challenge. As a consequence, stress engages a variety of physiological and neural processes with the ultimate objective of achieving optimal survival value, including the hypothalamo-pituitary-adrenocortical axis, the autonomic nervous system, and brain stress regulatory pathways that coordinate the behavior of the organism to fit desired outcomes. While initially adaptive, prolonged stress causes aberrant neuroplastic events in brain that have a long-term negative impact on physiology and behavior. My research is geared toward understanding the mechanisms underlying initiation of these neuroplastic events and their consequences on the individual. We have developed chronic stress paradigms that model physiological, metabolic and behavioral symptoms of depression (e.g., glucocorticoid dyshomeostasis; helplessness; anhedonia; cardiovascular pathology; visceral obesity) and PTSD (late-emerging, long-lasting potentiation of conditioned fear; late-emerging metabolic pathologies). We exploit these models to discover neurocircuit mechanisms mediating the deleterious effects of stress on neuroplasticity and behavior, focusing on corticolimbic pathways. Our work employs a broad spectrum of methods, including region/tissue-specific knockout in mice and rats; viral vector gene knockdown/ overexpression/CRISPR to modify gene expression in discrete brain regions; chemogenetic/optogenetic methods to modify brain activation in a site and projection specific manner; genomic approaches to understanding gene and epigenetic (microRNA) expression patterns in identified cell populations; mathematical modeling and bioinformatics; and state-of-the-art neuroanatomical approaches.
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