Accumulating evidence suggests that both intrinsic and extrinsic factors shape the function of neural circuits within certain substructures of the adult brain. A primary goal of my laboratory is to identify mechanisms by which blood-borne factors regulate brain function in the context of age-related disease. I recently demonstrated that the youth-associated blood-borne factor tissue inhibitor of metalloproteinases 2 (TIMP2) revitalizes hippocampal synaptic plasticity and cognition in aged mice. We are actively exploring how TIMP2 acts on circuits linked to learning and memory at molecular, morphological, and transcriptional levels of analysis. Given that its role in the brain is relatively unknown, we are creating a variety of genetic tools to begin probing the precise mechanism by which TIMP2 and its putative binding partners act to shape synaptic plasticity processes. A related goal of my group is to clarify the link between risk factors for neurodegenerative disease and the systemic environment. As such, another arm of the laboratory will focus on characterizing the extent to which blood-borne factors altered in the course of the normal aging process play a role in the pathogenesis of Alzheimer’s disease or other neurodegenerative disorders. We leverage both systems approaches as well as conventional molecular, cellular, and behavioral methodologies to understand how the brain’s learning and memory circuits are shaped by systemic influences in the setting of disease.