The Myelin Repair Foundation (MRF) Principal Investigators were selected based on their complementary knowledge and expertise, their past contributions to advancing our understanding of the key biological processes and interactions that control myelination and their common interest in developing treatments to repair myelin. Each investigator, along with the resources of their laboratories, is critical to MRF achieving its goals.
- Ben Barres, M.D., Ph.D., Stanford University
- Robert H. Miller, Ph.D., Case Western Reserve University
- Stephen D. Miller, Ph.D., Northwestern University
- Brian Popko, Ph.D., University of Chicago
Dr. Ben Barres is Professor of Neurobiology, Developmental Biology, and Neurology at Stanford Univeristy School of Medicine.
Dr. Barres's laboratory brings expertise in the development and function of glial cells in the mammalian central nervous system (CNS). They have found evidence of several novel glial signals that induce the onset of myelination, the clustering of axonal sodium channels, the survival and growth of retinal ganglion cells, and the formation of synapses.
Their work for MRF compliments Dr. Robert Miller's work on characterizing the processes related to myelination and identifying relevant glial-derived signaling molecules. To understand the interactions between axons and glial cells Dr. Barres's laboratory has developed methods to highly purify and culture neurons as well as oligodendrocytes and astrocytes (the glial cell types they interact with). The laboratory has developed a variety of novel methods to generate purified cell cultures that allow direct study of molecular interactions between the cell types and has considerable expertise in identifying and purifying these molecules.
All participating laboratories will rely on Dr. Barres's laboratory for its unique expertise in evaluating the action of target molecules using these novel cell purification and culture systems.
- Back to top -
Dr. Robert Miller is a Professor in the Department or Neurosciences at Case Western Reserve University School of Medicine.
Dr. Miller's laboratory brings expertise in defining the cellular and molecular factors that regulate glial cell determination in the vertebrate CNS and examining how proliferation and differentiation are controlled in the oligodendrocyte lineage in order to achieve the appropriate number of myelinating oligodendrocytes in the CNS. They also evaluate how glial cellular diversity is generated and what regulates the final glial composition of different regions of the CNS.
Dr. Miller's work complements Dr. Barres's for completing our understanding of the normal signaling and development of oligodendrocyte precursors into mature, myelinating oligodendrocytes. In addition, Dr. Miller's lab brings unique expertise in identifying, evaluating and validating MRF therapeutic targets in early stages of development and commitment, using both normal and diseased animal models and human tissue culture.
Dr. Miller's lab works closely with Dr. Barres's lab on identifying and validating developmental signaling pathways and the resulting therapeutic targets. His lab will also evaluate potential therapeutic targets identified by the other labs by their unique tissue culture capabilities.
- Back to top -
Dr. Stephen Miller is the Judy Gugenheim Research Professor of Biomedical Sciences, Professor of Microbiology-Immunology and Director of the Interdepartmental Immunobiology Center at Northwestern University.
Dr. Miller's laboratory investigates the immunological, cellular and molecular mechanisms of T cell-mediated autoimmune responses employing two mouse models of multiple sclerosis - Theiler's virus-induced model of MS and Relapsing Experimental Autoimmune Encephalomyelitis (R-EAE). The laboratory examines the mechanisms whereby self-tissue destruction results in activation and recruitment of autoreactive T/B cells specific for endogenous self antigens and molecular mimicry, the process that leads to induction and/or progression of autoimmunity.
Dr. Miller's expertise in the pathogenesis of autoimmunological disorders along with his specific expertise on the role of leukocytes in the regulation of myelination are critical to MRF achieving a comprehensive understanding of the endogenous molecular signals that mediate pathogenesis and prevent remyelination in MS.
Signaling mechanisms and molecules identified by Dr. Miller's lab that stimulate pathogenesis of myelin, will be validated in cell culture by Dr. Barres and Dr. Robert. Miller, and in genetically-modified mice by Dr. Popko.
Dr. S Miller's lab will perform similar evaluation services for targets identified by each of the other labs, in animal models developed by his lab. In addition, he will collaborate with Dr. Popko the development of new animal models that more closely mimic human MS, as necessary to validate MRF therapeutic targets.
- Back to top -
Dr. Brian Popko is the Jack Miller Professor of Neurological Diseases, Director of the Jack Miller Center for Peripheral Neuropathy and Associate Chair for Research in the Department of Neurology at the University of Chicago.
With a long-standing interest in disorders of the nervous system, Dr. Popko's work has centered on glial cells. Of particular interest to Dr. Popko's group are diseases like MS that disrupt the normal function of glial cells and the myelin sheath. Dr. Popko takes a molecular genetic approach to better understand these disorders using state-of-the-art techniques that allow for the manipulation of the mouse genome.
Dr. Popko's expertise in genetic manipulation to produce animal models that either do not produce a specific protein (knock-out), or that are induced to produce a non-native protein (transgenic), are essential in the validation of the pathogenic effects of therapeutic targets identified by all other MRF researchers.
In addition to testing the effects of target molecules identified by MRF researchers in these animal models, Dr. Popko will be working closely with Dr. Miller to develop new animal models that not only more closely mimic the pathogenesis of human MS, but also allow quantitative measurement of myelin formation. This is a critical step in proving the efficacy of MRF treatments.
- Back to top -
