James Lokensgard

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Credentials

PhD

Bio

Administrator Info
Name: Admin
Phone: 612-624-9996
Fax: 612-625-4410
Email: idimdivision@umn.edu
Mail: Microbiology Research Building, 1st floor mail room, MMC 2821, 689 23rd Ave S.E., Minneapolis, MN 55455

Summary
Research in our neurovirology laboratory specifically investigates the role of CNS-infiltrating peripheral immune cells in driving chronic activation of brain-resident glial cells following viral infection. We are currently investigating the role of CD19(-)CD38(+)CD138(+) plasma cells and antiviral antibodies persisting within the CNS during chronic herpesvirus brain infection. We are also applying our viral brain infection models to study experimental immune reconstitution disease of the CNS (CNS-IRD) using T-cell repopulation of lymphopenic hosts (MAIDS animals) harboring HSV brain infection. As well as in the brain, dysregulated chronic immune activation and immune cell infiltration likely promote analogous nerve damage and neurotoxicity within the lumbar spinal cord (LSC) and dorsal root ganglia (DRG). These findings have led us to new studies on the neuropathogenesis of LP-BM5 retrovirus infection (i.e., MAIDS)-induced peripheral neuropathy.

Research Summary

Our research laboratory studies the pathogenesis of viral brain infection in mice. We work in the field of neurovirology; which is at the interface of virology, immunology, and neuroscience. We are a biomedical research laboratory, working on modeling disease processes. We currently have two projects funded through individual R01 grants from the National Institutes of Health. In the first project, funded through NINDS, we are investigating whether recall immune responses from virus-specific, brain-resident memory T cells (bTRM) activate brain-resident glia and induce production of neurotoxic mediators. Our goal is to determine whether adaptive recall responses to viral Ag trigger tissue-wide innate immune responses from reactive glia and promote inflammation-induced synaptic damage, neurotoxicity, and long-term neurocognitive impairment. In our second project, which is funded through the NIMH, we are trying to determine whether glial cells are viable cellular targets for immunotherapy. Microglia are the main reservoir for HIV-1 within the brain and potential exists for negative immune checkpoint blockade immunotherapies to purge viral reservoirs. There is currently a great deal of research interest in using checkpoint inhibitors to purge HIV in “cure” strategies. The vast majority of these trials target the PD-1: PD-L1 pathway. In this project, we are investigating cytolytic responses of CD8+ T lymphocytes against primary microglia loaded with viral peptide epitopes to determine whether immune checkpoint blockade targeting this pathway may be beneficial in clearing viral brain reservoirs.