The John L. Trotter MS Center at Washington University Medical Center serves our community of patients through the partnership of Barnes-Jewish Hospital and Washington University School of Medicine.

Ongoing research at The John L. Trotter MS Center

Basic research

Multiple sclerosis (MS) is a complex disease of unknown etiology involving central nervous system (CNS) inflammation, demyelination and axonal damage. MS is generally believed to be an autoimmune disease consisting in an adaptive immune response (T and/or B cell mediated) directed against CNS myelin components.

Anne Cross, MD, is funded by grants from the National Institutes of Health, The Conrad N. Hilton Foundation and the National MS Society USA. Her laboratory studies utilize an animal model for MS (experimental autoimmune encephalomyelitis-EAE) to study the role of B cells, plasma cells and antibodies in inflammatory demyelination of the central nervous system. Other studies involve cutting edge imaging techniques to measure MS pathology in the central nervous system, and to observe neuropathological changes accompanying progressive disease in “real time.” Cross’ laboratory also investigates the effects of approved medications for MS, to better understand how they achieve efficacy.

Research from Laura Piccio, MD, PhD, investigates the role played by the immune system in MS pathogenesis and utilizes human specimens obtained from MS subjects, as well as the EAE model. Her goals are to apply basic research findings to the clinic. Currently, Piccio’s research focuses on two major areas: the Role of Innate Immune Cells and the Complex Interactions Between the Immune System and Metabolism in MS and EAE.

The goal of the Wu lab is to determine the requirements for antigen presentation during immune responses within the central nervous system. Several ongoing projects involve the use of an animal model system called experimental autoimmune encephalomyelitis (EAE). First, because there is strong clinical and experimental evidence that B cells contribute to MS via their role as antigen presenting cells, we have used a genetically engineered tool we have recently developed for the conditional expression of MHCII to explore the extent to which B cells alone can drive CD4 T cell auto-reactivity in vivo. We have found that antigen presentation by B cells alone is not sufficient to support passive EAE resulting from transfer of encephalitogenic CD4 T cells unless B cells also express antigen receptor specific for cognate antigen. We are exploring the mechanisms by which B cells regulate CD4 T cell function during EAE. Second, we are examining the role of dendritic cells (DCs), a special class of antigen presenting cell thought to be involved in the pathogenesis of central nervous system inflammation. Currently, EAE serves as the experimental basis for this work, although an initial collaboration with the Cross and Piccio labs is underway to extend this research focus into human clinical trials. Third, we have observed a role for the lipid binding protein apolipoprotein E (apoE) during EAE. We hypothesize that production of apoE by DCs and other innate cells functions to enhance myelin antigen capture and processing. To investigate the role of apoE in antigen presentation during EAE, we have used in vivo genetic manipulation of apoE. We have found changes in CD4 T cell myelin-reactivity in apoE-deficient mice that is associated with a reduction in severity of disease. We aim to continue to explore the mechanisms involved in apoE-mediated CD4 T cell responses using a variety of techniques, including cell culture, imaging, and flow cytometry. Funding for these studies currently comes from the NINDS and National Multiple Sclerosis Society.

Robyn Klein, MD, PhD, associate professor in the departments of Internal Medicine, Pathology and Immunology, and Anatomy and Neurobiology, is funded by grants from the National Institutes of Health, the National Multiple Sclerosis Society and the Dana Foundation. Her laboratory utilizes both in vitro and in vivo models to define molecular mechanisms of leukocyte entry into the CNS, blood-brain barrier dysfunction and CNS repair including remyelination. The actions and regulation of chemokines, which play roles in all of these processes, is of particular interest, as well as innate immune mechanisms that may both promote and prevent neuropathology. Visit the Klein lab website for more information.