Current Research and Scholarly Interests
From recent advances in GWAS and systems biology, as well as our own work, a dominant role for the microglial immune response has emerged in AD development. More generally, a maladaptive immune response is likely to be a common denominator across many neurological disorders, both acute (brain trauma or stroke) and chronic (epilepsy, AD, Parkinson?s disease, for eg.) as well as in psychiatric disorders like depression and PTSD, where excessive microglial activity has now been demonstrated. Therefore, an understanding of how microglial responses cause neurological disease will be essential if we are to develop disease-modifying therapies for our patients. Through a systems biology approach, my laboratory is identifying novel immune pathways that may play a critical role in maladaptive brain inflammation, and we are working to understand how these responses cause neurodegeneration and circuit disruption. Our two main objectives are (1) to understand how aberrant microglial responses cause synapse loss and how that contributes 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.