James R. Lokensgard, PhD, MS, BA

Professor of Medicine, Division of Infectious Diseases and International Medicine

James R. Lokensgard

Contact Info

Mailing Address:
3-107 Microbiology Research Facility
689 23rd Ave SE
Minneapolis, Minnesota 55455-1507
UM Delivery Code: 2821A

Lab Address:
1-137 Microbiology Research Facility

Administrative Assistant Name
Debbie Rootes

Administrative Phone
612-624-1966

Administrative Email
roote001@umn.edu

Administrative Fax Number
612-301-1292

Postdoctoral Fellow, University of California, Los Angeles, CA

PhD, University of Minnesota, Minneapolis, MN

MS, North Dakota State University, Fargo, ND

B.A., Saint Cloud State University

Post-doctoral training, University of California, Los Angeles, CA

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

Research Summary/Interests

  • Viral brain infections

Dr. Lokensgard's laboratory currently performs studies supporting two independent research programs in neurovirology. The first program investigates host defense mechanisms against cytomegalovirus brain infection. Our experiments investigate how glial cell-produced chemokines recruit peripheral lymphocytes into the brain to control intracerebral spread of MCMV. The Laboratory's other program studies the immunoregulation of herpes simplex virus (HSV) encephalitis by microglial cells. We are investigating how chemokines produced by microglial cells in response to HSV infection initiate cascades of neuroimmune responses that result in the serious brain damage seen during herpes encephalitis. Knowledge gained from these studies will increase our understanding of the role of chemokine networks in regulating brain inflammation with the ultimate goal of finding new therapy for serious viral brain infections.

Publications

  • Aravalli RN, Hu S, Lokensgard JR. 2008. Inhibition of toll-like receptor signaling in primary murine microglia. J Neuroimmune Pharmacol. 3(1):5-11. Epub 2007 Dec 5.
  • Cheeran MC, Hu S, Palmquist JM, Bakken T, Gekker G, Lokensgard JR. 2007. Dysregulated interferon-gamma responses during lethal cytomegalovirus brain infection of IL-10-deficient mice. Virus Res. 130(1-2):96-102. Epub 2007 Jul 12.
  • Sheng WS, Hu S, Herr G, Ni HT, Rock RB, Gekker G, Lokensgard JR, Peterson PK. 2007. Human neural precursor cells express functional kappa-opioid receptors. J Pharmacol Exp Ther. 322(3):957-63. Epub 2007 May 30.
  • Aravalli RN, Hu S, Lokensgard JR. 2007. Toll-like receptor 2 signaling is a mediator of apoptosis in herpes simplex virus-infected microglia. J Neuroinflammation. J Neuroinflammation. 4:11.
  • Aravalli RN, Hu S, Rowen TN, Gekker G, Lokensgard JR. 2006. Differential apoptotic signaling in primary glial cells infected with herpes simplex virus 1. J Neurovirol. 12(6):501-10.
  • Hu S, Cheeran MC, Sheng WS, Ni HT, Lokensgard JR, Peterson PK. 2006. Cocaine alters proliferation, migration, and differentiation of human fetal brain-derived neural precursor cells. J Pharmacol Exp Ther. 318(3):1280-6. Epub 2006 Jun 9.
  • Gekker G, Hu S, Sheng WS, Rock RB, Lokensgard JR, Peterson PK. 2006. Cocaine-induced HIV-1 expression in microglia involves sigma-1 receptors and transforming growth factor-beta1. Int Immunopharmacol. 6(6):1029-33. Epub 2006 Jan 13.
  • Marques CP, Hu S, Sheng W, Lokensgard JR. 2006. Microglial cells initiate vigorous yet non-protective immune responses during HSV-1 brain infection. Virus Res. 121(1):1-10. Epub 2006 Apr 18.
  • Cheeran MC, Hu S, Sheng WS, Rashid A, Peterson PK, Lokensgard JR. 2005. Differential responses of human brain cells to West Nile virus infection. J Neurovirol. 11(6):512-24.
  • Sheng WS, Hu S, Ni HT, Rowen TN, Lokensgard JR, Peterson PK. 2005. TNF-alpha-induced chemokine production and apoptosis in human neural precursor cells. J Leukoc Biol. 78(6):1233-41.
  • Cheeran MC, Hu S, Ni HT, Sheng W, Palmquist JM, Peterson PK, Lokensgard JR. 2005. Neural precursor cell susceptibility to human cytomegalovirus diverges along glial or neuronal differentiation pathways. J Neurosci Res. 82(6):839-50.
  • Aravalli RN, Hu S, Rowen TN, Palmquist JM, Lokensgard JR. 2005. Cutting edge: TLR2-mediated proinflammatory cytokine and chemokine production by microglial cells in response to herpes simplex virus. J Immunol. 175(7):4189-93.
  • Gekker G, Hu S, Spivak M, Lokensgard JR, Peterson PK. 2005. Anti-HIV-1 activity of propolis in CD4(+) lymphocyte and microglial cell cultures. J Ethnopharmacol.102(2):158-63. Epub 2005 Jul 19.
  • Cheeran MC, Gekker G, Hu S, Palmquist JM, Lokensgard JR. 2005. T cell-mediated restriction of intracerebral murine cytomegalovirus infection displays dependence upon perforin but not interferon-gamma. J Neurovirol. 11(3):274-80.
  • Hu S, Sheng WS, Lokensgard JR, Peterson PK. 2005. Morphine potentiates HIV-1 gp120-induced neuronal apoptosis. J Infect Dis. 191(6):886-9. Epub 2005 Feb 10.
  • Sheng WS, Hu S, Min X, Cabral GA, Lokensgard JR, Peterson PK. 2005. Synthetic cannabinoid WIN55,212-2 inhibits generation of inflammatory mediators by IL-1beta-stimulated human astrocytes. Glia. 49(2):211-9.
  • Ni HT, Hu S, Sheng WS, Olson JM, Cheeran MC, Chan AS, Lokensgard JR, Peterson PK. 2004. High-level expression of functional chemokine receptor CXCR4 on human neural precursor cells. Brain Res Dev Brain Res. 152(2):159-69.
  • Marques CP, Hu S, Sheng W, Cheeran MC, Cox D, Lokensgard JR. 2004. Interleukin-10 attenuates production of HSV-induced inflammatory mediators by human microglia. Glia. 47(4):358-66.
  • Cheeran MC, Gekker G, Hu S, Min X, Cox D, Lokensgard JR. 2004. Intracerebral infection with murine cytomegalovirus induces CXCL10 and is restricted by adoptive transfer of splenocytes. J Neurovirol. 10(3):152-62.
  • Gekker G, Hu S, Wentland MP, Bidlack JM, Lokensgard JR, Peterson PK. 2004. Kappa-opioid receptor ligands inhibit cocaine-induced HIV-1 expression in microglial cells. J Pharmacol Exp Ther. 309(2):600-6. Epub 2004 Feb 2.
  • Peterson PK, Gekker G, Hu S, Cabral G, Lokensgard JR. 2004. Cannabinoids and morphine differentially affect HIV-1 expression in CD4(+) lymphocyte and microglial cell cultures. J Neuroimmunol. 147(1-2):123-6.
  • Cheeran MC-J, Hu S, Sheng WS, Peterson PK, Lokensgard JR. 2003. CXCL10 production from cytomegalovirus-stimulated microglia is regulated by both human and viral interleukin-10. J Virol. 77:4502-4515.
  • Lokensgard JR, Gekker G, Peterson PK. 2002. k-Opioid receptor agonist inhibition of HIV-1 envelope glycoprotein-mediated membrane fusion and CXCR4 expression on CD4+ lymphocytes. Biochem Pharmacol. 63:1037-1041.
  • Lokensgard JR, Cheeran MC-J, Hu S, Gekker G, and Peterson PK. 2002. Glial cell responses to herpesvirus infections: role in defense and pathogenesis. J Infect Dis. 186 (Suppl 2):S171-S179.