Thomas Lane

Professor of Pathology

Tom Lane

B.S. Ball State University

Ph.D. University of California, Los Angeles

Research

References

tom.lane@path.utah.edu

Thomas Lane's Lab Page

Thomas Lane's PubMed Literature Search

Molecular Biology Program

Virus, central nervous system neuroimmunology, stem cells, demyelination

Research

Work in my laboratory is divided into two main research areas: 1) define the functional contributions of chemokines and chemokine receptors in defense and disease following viral infection of the central nervous system (CNS) and 2) evaluate the therapeutic potential of mouse/human neural precursor cells (NPCs) in clinical recovery and remyelination in a model of viral-induced demyelination.

My laboratory has a long-standing interest in understanding events that initiate and maintain inflammation within the CNS in response to viral infection. To this end, we have set forth on a directed path to determine the functional significance of chemokines and chemokine receptors in both host defense as well as disease development following instillation of a positive-strand RNA virus (mouse hepatitis virus – MHV) into the CNS of susceptible mice. Indeed, we have shown that blocking chemokine function via both antibody neutralization and genetic silencing in virally-infected mice resulted in increased mortality accompanied by reduced immune cell infiltration into the CNS. Subsequently, we have demonstrated that unique chemokine/chemokine receptor signaling pathways are critical for interrelated events required for optimal host defense following viral infection including linking innate and adaptive immune responses, regulating antiviral effector functions e.g. cytokine secretion/cytolytic activity by effector T cells, and promoting the directional migration of antigen-sensitized lymphocytes into the CNS. We have also focused on how chemokine signaling influences the biology of oligodendroglia with regards to protection from inflammatory cytokine-induced apoptosis.

Similar to the human demyelinating disease multiple sclerosis (MS), remyelination failure is also observed in MHV-infected mice. Therefore, an important and clinically-relevant question related to demyelinating diseases is to design therapies that promote remyelination of demyelinated axons. We have determined that surgical engraftment of mouse neural precursosr cells (NPCs) into mice persistently-infected with MHV results in survival and migration of engrafted NPCs accompanied by extensive remyelination. The use of a viral model of demyelination is relevant in that the etiology of MS remains enigmatic and viruses have long been considered important as a potential triggering agent in inducing demyelinating diseases. Moreover, numerous viruses are capable of persisting within the CNS therefore understanding if NPCs are capable of promoting repair within an environment in which a persistent virus is present resulting in chronic neuroinflammation/demyelination is critical. We have determined that transplanted cells migrate to areas of demyelination by responding to the specific chemokines expressed within areas of demyelination. We have now moved forward with our studies on NPC-mediated clinical/histological recovery to address whether allogeneic NPCs are antigenic and subject to immune-mediated rejection. We are also investigating the therapeutic potential of human NPCs (hNPCs) in mediating functional recovery following transplantation into MHV-infected mice.

 Selected Publications

  1. Herzm J., P. Sabellek, T.E. Lane, M. Gunzer, D.M. Hermann, and T.R. Doeppner (2015). Role of neutrophils in exacerbation of brain injury after focal cerebral ischemia in hyperlipidemic mice. Stroke 46(10):2916-25.
  2. Marro, B.S., J.J. Grist, and T.E. Lane (2016). Inducible expression of CXCL1 within the central nervous system amplifies viral-induced demyelination. J Immuno 196(4):1855-64.
  3. Marsh, S.E., E.M. Abud, A. Lakatos, A. Karimzadeh, S.T. Yeung, H. Davtyan, G. Fote, L. Lau, J.G. Weinger, T.E. Lane, M.A. Inlay, W.W. Poon, and M. Blurton-Jones (2016). The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglia function. PNAS 113(9):E1316-25.
  4. Plaisted, W.C., A. Zavala, E. Hingco, H. Tran, R. Coleman, T.E. Lane, J.F. Loring, and C.M. Walsh (2016). Remyelination Is Correlated with Regulatory T Cell Induction Following Human Embryoid Body-Derived Neural Precursor Cell Transplantation in a Viral Model of Multiple Sclerosis. PLoS One 11(6):e0157620.
  5. Blanc, C.A., J.J. Grist, H. Rosen, I. Sears-Kraxberger, O. Steward, and T.E. Lane (2015). Sphingosine-1-phosphate receptor antagonism enhances proliferation and migration of engrafted neural progenitor cells in a model of viral-induced demyelination. Am J Pathol 185(10):2819-32.
  6. Chen, L., R. Coleman, R. Leang, A. Kopf, C.M. Walsh, W. Macklin, J.F. Loring and T.E. Lane (2014). Human neural precursor cells promote neurologic recovery in a viral model of multiple sclerosis. Stem Cell Reports 2(6): 825-37.
  7. Weinger, J.G., W.C. Plaisted, S.M. Maciejewski, L.L. Lanier, C.M. Walsh, and T.E. Lane (2014). Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis. Stem Cells 32(10):2690-701.
  8. Greenberg, M.L., J.G. Weinger, M.P. Matheu, K.S. Carbajal, I. Parker, W.B. Macklin, T.E. Lane*, and M.D. Cahalan* (2014). Two-photon imaging demonstrates remyelination of spinal cord axons by engrafted neural precursor cells in a model of multiple sclerosis. PNAS 111(22): E2349-55.
  9. Chucair-Elliott, A.J., M. Zhen, C.M. Kroll, T.E. Lane, and D.J.J. Carr (2014). Microglia-induced IL-6 protects against neuronal loss following HSV-1 infection of neural progenitor cells. Glia 62(9):1418-34.
  10. Weinger, J.G., L. Chen, R. Coleman, R. Leang, W. Plaisted, J.F. Loring, and T.E. Lane (2013). Intraspinal transplantation of mouse and human neural precursor cells. Current Protocols in Stem Cell Biology 26:Unit 2D.16.
  11. Plaisted, W.C., J.G. Weinger, C.M. Walsh, and T.E. Lane (2014). T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells. Virology 449:235-43.
  12. Villegas-Mendez, A., E.G. Findlay, L.M. Grady, J.B. de Souza, C.J. Saris, T.E. Lane, E.M. Riley, and K.N. Couper (2013). WSX-1 signalling inhibits CD4⁺ T cell migration to the liver during malaria infection by repressing chemokine-independent pathways. PLoS One 8(11): e78486.
  13. Weinger, J.G., B.S. Marro, M. Hosking, and T.E. Lane (2013). The chemokine receptor CXCR2 and coronavirus-induced neurologic disease. Virology 435(1): 110-7.
  14. Nance, J.P., K.M. Vannella, D. Worth, C. David, D. Carter, S. Noor, C. Hubeau, L. Fitz, T.E. Lane, T.A. Wynn, and E.H. Wilson (2012). Chitinase dependent control of protozoan cyst burden in the brain. PLoS Pathogens 8(11): e1002990.
  15. Tirotta, E., P. Duncker, J. Oak, S. Klaus, M.R. Tsukamoto, L. Gov, and T.E. Lane (2012). Epstein-Barr virus-induced gene 3 negatively regulates neuroinflammation and T cell activation following coronavirus-induced encephalomyelitis. J. Neuroimmunology 254(1-2): 110-6.
  16. Zhao, J., C. Wohlford-Leanne, J. Zhao, T.E. Lane, P. McCray, and S. Perlman (2012). Treatment with toll-lie receptor agonists protects aged mice from lethal respiratory viral infection. J. Virology 86(21): 11416-24.
  17. Weinger, J.G., B.M. Weist, W.C. Plaisted, S.M. Klaus, C.M. Walsh, and T.E. Lane (2012). MHC mismatch results in neural progenitor cell rejection following spinal cord transplantation in a model of viral-induced demyelination. Stem Cells 30(11): 2584-95.
  18. Tirotta, E., L.A. Kirby, M.N. Hatch, and T.E. Lane (2012). IFN-g-induced apoptosis of human embryonic stem cell derived oligodendrocyte progenitor cells is restricted by CXCR2 signaling. Stem Cell Research 9(3): 208-217.
  19. Marro, B.S., M.P. Hosking, and T.E. Lane (2012). CXCR2 signaling and host defense following coronavirus-induced encephalomyelitis. Future Virology 7(4): 349-59.
  20. Whitman, L.M., C. Blanc, C.S. Schaumburg, D.H. Rowitch, and T.E. Lane (2012). Olig 1 function is required for remyelination potential of transplanted neural progenitor cells in a model of viral-induced demyelination. Exp. Neuro. 235(1): 380-7. 
  21. Liu, J.Z., S. Jellbauer, A. Poe, V. Ton, M. Pesciaroli, T. Kehl-Fie, N.A. Restrepo, M. Hosking, R.A. Edwards, A. Battistoni, P. Pasquali, T.E. Lane, W.J. Chazin, T. Vogl, J. Roth, E.P. Skaar, and M. Raffatellu (2012). Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut. Cell Host Microbe 11(3): 227-39.
  22. Lu, J., B.M. Weist, B. van Raam, B. Marro, L.V. Nguyen, P. Srinivas, B.D. Bell, K.A. Luhrs, T.E. Lane, G.S. Salvesen, and C.M. Walsh (2011). Complementary roles of Fas-associated death domain protein (FADD) and receptor interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral immunity. Proc. Natl. Acad. Sci. USA. 108(37): 15312-7.
  23. Carbajal, K.S., J.L. Miranda, M.R. Tsukamoto, and T.E. Lane (2011). CXCR4 signaling regulates remyelination by endogenous oligodendrocyte progenitor cells in a viral model of demyelination. Glia 59(12): 1813-21.
  24. Tirotta, E., R.M. Ransohoff, and T.E. Lane (2011). CXCR2 signaling protects oligodendrocyte progenitor cells from IFN-g/CXCL10-mediated apoptosis. Glia 59(10): 1518-28.
  25. Sy, M., M. Kitazawa, R. Medeiros, L. Whitman, D. Cheng, T.E. Lane, and F.M. LaFerla (2011). Inflammation induced by infection potentiates tau pathology in transgenic mice. American J. Pathology 178(6): 2811-22.
  26. Kohler, A., K. De Filippo, M. Hasenberg, C. Nitschke, E. Nye, M.P. Hosking, T.E. Lane, L. Mann, R.M. Ransohoff, A.E. Hauser, W. Winter, B. Schraven, H. Geiger, N. Hogg, and M. Gunzer (2011). Thrombopoietin-stimulated megakaryocytes control neutrophil motility and mobilization from bone marrow by release of CXCR2 ligands. Blood 117(16): 4349-4357.
  27. Liu, L., L. Darnall, T. Hu, K. Choi, T.E. Lane, and R.M. Ransohoff (2010). Myelin repair is accelerated by inactivating CXCR2 on nonhematopoietic cells. J. Neuroscience 30(27): 9074-83.
  28. Tirotta, E., K.S. Carbajal, C.S. Schaumburg, L. Whitman, and T.E. Lane (2010). Cell replacement therapies to promote remyelination in a viral model of demyelination. J. Neuroimmunology 224(1-2): 101-7.
  29. Denes, A., N.Humphreys, T.E. Lane, R. Grencis, and N. Rothwell (2010). Chronic systemic infection exacerbates ischaemic brain damage via a CCL5 (RANTES) mediated proinflammatory response. J. Neuroscience 30(30): 10086-95.
  30. Hosking, M.P., E. Tirotta, R.M. Ransohoff, and T.E. Lane (2010). CXCR2 signaling protects oligodendrocytes and restricts demyelination in a mouse model of viral-induced demyelination. PLoS One 5(6): e11340.
  31. Carbajal, K.S., C. Schaumburg, R. Strieter, J. Kane, and T.E. Lane (2010). Migration of engrafted neural stem cells is mediated by CXCL12 signaling through CXCR4 in a viral model of multiple sclerosis. Proc Natl Acad Sci U S A 107(24): 11068-73.
  32. Hosking, M.P. and T.E. Lane (2010). The role of chemokines during viral infection of the CNS. Pearl Article: PLoS Pathogens 6(7): e1000937.
  33. Liu, L., A. Belkadi, L. Darnall, T. Hu, C. Drescher, A.C. Cotleur, D. Padovani-Claudio, T. He, K. Choi, T.E. Lane, R.H. Miller, and R.M. Ransohoff (2010). CXCR2+ neutrophils play an essential role in cuprizone-induced demyelination: relevance to multiple sclerosis. Nature Neuroscience 13(3): 319-326.
  34. Hosking, M.P. and T.E. Lane (2009). The biology of persistent infection: Inflammation and demyelination following murine coronavirus infection of the central nervous system. Current Immuno. Rev. 5(4): 267-276.
  35. Hosking, M.P., L. Liu, R.M. Ransohoff, and T.E. Lane (2009). A protective role for ELR+ chemokines during acute viral encephalomyelitis. PLoS Pathogen 5(11): e1000648.

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Last Updated: 11/2/16