Thomas E. Lane
Professor of Pathology
Neurobiology of Disease
e-mail: tom.lane@path.utah.edu
B.S. 1988, Ball State University; Ph.D. 1993, University of California, Los Angeles; Postdoctoral Fellow 1993-1997, The Scripps Research Institute
RESEARCH:
Neural Stem Cells, Multiple Sclerosis, Virology
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.