Joel S. Pachter, PhD

The major focus in this laboratory is to elucidate the mechanisms by which leukocytes and pathogens invade the central nervous system (CNS). Movement of both soluble and cellular elements into the CNS is regulated by microvessel endothelial cells comprising the blood-brain barrier (BBB). It is thus believed that alterations in the BBB contribute to the pathogenesis of various neuroinflammatory, neuroinfectious and neurodegenerative diseases such as multiple sclerosis, AIDS dementia complex and Alzheimer disease. To evaluate the role played by the BBB in these disorders, we are employing an in vitro culture model of the human BBB recently developed in this laboratory. Studies in progress in this laboratory include the following: 1.) Analysis of cell-targeted chemokine knockouts (developed in this laboratory) to determine the role of site-specific release of chemokines in neuroinflammatory disease. 2.)Assessing how normal aging affects cerebral angiogenesis in different brain regions, and the role of different exercise regimens in modifying age-related affects on cerebrovascular properties. 3.)Using laser capture microdissection (LCM) coupled with gene array and proteomic platforms to characterize the extent and nature of heterogeneity along the microvascular tree of the central nervous system. 4.)Using LCM to probe changes in the blood-brain barrier that accompany cerebral ischemia.

[2025] Immuno-laser capture microdissection of perfusion-fixed mouse brain tissue coupled to RNA-seq. [2023] Host extracellular vesicles confer cytosolic access to systemic LPS licensing non-canonical inflammasome sensing and pyroptosis. [2023] Proteomic interrogation of the meninges reveals the molecular identities of structural components and regional distinctions along the CNS axis.