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We are investigating the role that innate immune responses play in the initiation and progression of neurological diseases. Recent advances in human genetics, particularly for neurodegenerative disorders like Alzheimer’s disease, have highlighted a causal role for a disrupted immune response in disease pathogenesis. An injurious immune response may be a common denominator across many neurological disorders, both acute (brain trauma or stroke) and chronic (epilepsy, Parkinson’s disease, Alzheimer's for eg.). An understanding of how innate immune responses cause neurological disease will be essential if we are to develop disease-modifying therapies for our patients. Through a systems biology approach, we are identifying novel immune pathways that may play critical roles in maladaptive brain inflammation, and we are working to understand how these responses cause neurodegeneration and circuit disruption. Some of these new pathways are relevant to immune cell metabolism and the effect of metabolic regulators of immune function. Our objectives are (1) to understand how aberrant CNS and/or peripheral innate immune responses cause synapse loss and contribute to the vulnerability of selected circuits in different neurodegenerative disorders, and (2) to develop preventive and therapeutic strategies targeting these inflammatory pathways in patients with neurologic diseases.