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Thomas E. Lane
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Phone: 801-585-5558
Office: 2600C Emma Eccles Jones

Thomas E. Lane

Professor
Adjunct Professor, Bioengineering
B.S.- Ball State University
Ph.D. - UCLA School of Medicine
Postdoc - Scripps Research Institute, La Jolla CA

Research

Neuroinflammation, Demyelinating Diseases, Neural Stem Cells


Current Research

Work in my laboratory is divided into two main research areas: 1) chemokines and chemokine receptors in defense and disease following microbial infection and 2) mouse/human neural progenitor cells (NPCs) and remyelination following viral-induced demyelination. Below, I highlight funded research ongoing within the laboratory.
1. Chemokines and chemokine receptors in defense and disease following viral infection of the CNS.
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 were the first laboratory to show 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 shown 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.
2. Mouse/human neural progenitor cells (NPCs) and remyelination following viral-induced demyelination.
MHV infection of the CNS results in viral persistence in white matter tracts leading to chronic infiltration of activated lymphocytes and macrophages that contribute to demyelination. Importantly, generation of autoreactive T lymphocytes specific for myelin proteins e.g. myelin basic protein (MBP) and proteolipid protein (PLP) is not prevalent therefore epitope-spreading is not a relevant aspect in this model system. Additionally, MHV-induced demyelination results in moderate-to-severe clinical disease characterized by hind-limb paralysis. 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 previously shown that surgical engraftment of syngeneic neural progenitor cells (NPCs) into mice persistently-infected with MHV results in survival and migration of engrafted NPCs accompanied by extensive remyelination. We are the only group, to my knowledge, examining the therapeutic potential of cell replacement strategies using a viral model of demyelination. This is important in that the etiology of MS remains enigmatic and viruses have long been considered important as a potential triggering agent in inducing demyelinating diseases such as MS. Moreover, numerous viruses are capable of persisting within the CNS therefore understanding if NPCs are capable of promoting repair within this environment 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. We have determined that intraspinal transplantation of hNPCs into MHV-infected mice results in rapid rejection. Therefore, we are now interrogating mechanisms by which to prolong hNPC surv


Selected Publications

Mangale V, Marro BS, Plaisted WC, Walsh CM, Lane TE, Neural precursor cells derived from induced pluripotent stem cells exhibit reduced susceptibility to infection with a neurotropic coronavirus. Virology 2017 Aug 16;511:49-55

Dickey LL, Hanley TM, Huffaker TB, Ramstead AG, O'Connell RM, Lane TE, MicroRNA 155 and viral-induced neuroinflammation. J Neuroimmunol 2017 Jul 15;308:17-24

Lane TE, Preface. J Neuroimmunol 2017 Jul 15;308:1

Soto R, Petersen C, Novis CL, Kubinak JL, Bell R, Stephens WZ, Lane TE, Fujinami RS, Bosque A, O'Connell RM, Round JL, Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor. Proc Natl Acad Sci U S A 2017 May 23;114(21):5497-5502

Klein RS, Voskuhl R, Segal BM, Dittel BN, Lane TE, Bethea JR, Carson MJ, Colton C, Rosi S, Anderson A, Piccio L, Goverman JM, Benveniste EN, Brown MA, Tiwari-Woodruff SK, Harris TH, Cross AH, Speaking out about gender imbalance in invited speakers improves diversity. Nat Immunol 2017 Apr 18;18(5):475-478

Dickey LL, Worne CL, Glover JL, Lane TE, O'Connell RM, MicroRNA-155 enhances T cell trafficking and antiviral effector function in a model of coronavirus-induced neurologic disease. J Neuroinflammation 2016 Sep 7;13(1):240

Grist JJ, Marro B, Lane TE, Neutrophils and viral-induced neurologic disease. Clin Immunol 2016 Jun 8;:

Marro BS, Grist JJ, Lane TE, Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination. J Immunol 2016 Feb 15;196(4):1855-64

Plaisted WC, Zavala A, Hingco E, Tran H, Coleman R, Lane TE, Loring JF, Walsh CM, 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 2016;11(6):e0157620

Yandamuri SS, Lane TE, Imaging Axonal Degeneration and Repair in Preclinical Animal Models of Multiple Sclerosis. Front Immunol 2016;7:189

Blanc CA, Grist JJ, Rosen H, Sears-Kraxberger I, Steward O, Lane TE, Sphingosine-1-phosphate receptor antagonism enhances proliferation and migration of engrafted neural progenitor cells in a model of viral-induced demyelination. Am J Pathol 2015 Oct;185(10):2819-32

Herz J, Sabellek P, Lane TE, Gunzer M, Hermann DM, Doeppner TR, Role of Neutrophils in Exacerbation of Brain Injury After Focal Cerebral Ischemia in Hyperlipidemic Mice. Stroke 2015 Oct;46(10):2916-25

Weinger JG, Greenberg ML, Matheu MP, Parker I, Walsh CM, Lane TE, Cahalan MD, Two-photon imaging of cellular dynamics in the mouse spinal cord. J Vis Exp 2015 Feb 22;(96):

Weinger JG, Plaisted WC, Maciejewski SM, Lanier LL, Walsh CM, Lane TE, Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis. Stem Cells 2014 Oct;32(10):2690-701

Held KS, Lane TE, Spinal cord injury, immunodepression, and antigenic challenge. Semin Immunol 2014 Oct;26(5):415-20

Chucair-Elliott AJ, Conrady C, Zheng M, Kroll CM, Lane TE, Carr DJ, Microglia-induced IL-6 protects against neuronal loss following HSV-1 infection of neural progenitor cells. Glia 2014 Sep;62(9):1418-34

Libbey JE, Lane TE, Fujinami RS, Axonal pathology and demyelination in viral models of multiple sclerosis. Discov Med 2014 Jul-Aug;18(97):79-89

Chen L, Coleman R, Leang R, Tran H, Kopf A, Walsh CM, Sears-Kraxberger I, Steward O, Macklin WB, Loring JF, Lane TE, Human neural precursor cells promote neurologic recovery in a viral model of multiple sclerosis. Stem Cell Reports 2014 Jun 3;2(6):825-37

Greenberg ML, Weinger JG, Matheu MP, Carbajal KS, Parker I, Macklin WB, Lane TE, Cahalan MD, Two-photon imaging of remyelination of spinal cord axons by engrafted neural precursor cells in a viral model of multiple sclerosis. Proc Natl Acad Sci U S A 2014 Jun 3;111(22):E2349-55

Blanc CA, Rosen H, Lane TE, FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination. J Neuroinflammation 2014 Aug 20;11:138

Hosking MP, Lane TE, ELR(+) chemokine signaling in host defense and disease in a viral model of central nervous system disease. Front Cell Neurosci 2014;8:165

Plaisted WC, Weinger JG, Walsh CM, Lane TE, T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells. Virology 2014 Jan 20;449:235-43

Tsunoda I, Lane TE, Blackett J, Fujinami RS, Distinct roles for IP-10/CXCL10 in three animal models, Theiler's virus infection, EAE, and MHV infection, for multiple sclerosis: implication of differing roles for IP-10. Mult Scler 2004 Feb;10(1):26-34