This proposal describes a 5-year training program for the development of an academic career in neuroimmunology. The PI has previous training in neuroscience, completed formal residency training in neurology, and is currently expanding his clinical skills in multiple sclerosis and scientific skills in neuroimmunology research. Drs. Terri Laufer and Gary Koretzky, internationally recognized authorities in immunology, will mentor the Pi's scientific development. Dr. Laufer is a rheumatology clinician-scientist well regarded for her diverse work in autoimmunity. Dr. Koretzky, the Vice Chair for Research in the Department of Medicine and endowed Professor in Pathology, has mentored numerous students, post-doctoral fellows and junior faculty members. To further promote the investigator's scientific development, an Advisory Committee comprising highly regarded medical scientists with expertise in neuroimmunology, including Drs. Francisco A. Gonzalez-Scarano, Steven Reiner, Youhai Chen and Michael K. Racke, has been established. The proposed research focuses on the role of dendritic cells in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Multiple sclerosis is an inflammatory, demyelinating disease of the central nervous system. The process involved in generating the auto-reactive CD4 T cells required for EAE is unclear. Dendritic cells are a special class of antigen presenting cell capable of activating CD4 T cells and initiating a wide array of effector functions. Dendritic cells are thought to be important during multiple phases of disease in EAE. Therefore, understanding the contributions of dendritic cells to EAE is of particular relevance to the pathogenesis of multiple sclerosis. Given the mentor's expertise in T cell-dendritic cell interactions in autoimmunity, Dr. Laufer's laboratory is the ideal setting to study the precise roles played dendritic cells during inflammatory responses targeting the central nervous system.
Specific aims i nclude: 1) defining the mechanisms for dendritic cell-dependent CD4 T cell activation in EAE, and 2) studying the contributions of different subsets of dendritic cells during various phases of EAE. The quality of the research facilities and the diversity of the resources available at the sponsoring institution, in combination with the intellectual and academic strength of the sponsors, provide an ideal environment in which to conduct this proposed training program.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS062138-05
Application #
8279435
Study Section
NST-2 Subcommittee (NST)
Program Officer
Utz, Ursula
Project Start
2008-09-01
Project End
2013-08-30
Budget Start
2012-07-01
Budget End
2013-08-30
Support Year
5
Fiscal Year
2012
Total Cost
$168,804
Indirect Cost
$12,504
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Shin, Soomin; Walz, Katharine A; Archambault, Angela S et al. (2014) Apolipoprotein E mediation of neuro-inflammation in a murine model of multiple sclerosis. J Neuroimmunol 271:8-17
Barnett, Lisa G; Simkins, Helen M A; Barnett, Burton E et al. (2014) B cell antigen presentation in the initiation of follicular helper T cell and germinal center differentiation. J Immunol 192:3607-17
Satake, Atsushi; Schmidt, Amanda M; Archambault, Angela et al. (2013) Differential targeting of IL-2 and T cell receptor signaling pathways selectively expands regulatory T cells while inhibiting conventional Týýcells. J Autoimmun 44:13-20
Koval, Erica D; Shaner, Carey; Zhang, Peter et al. (2013) Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice. Hum Mol Genet 22:4127-35
Archambault, Angela S; Carrero, Javier A; Barnett, Lisa G et al. (2013) Cutting edge: Conditional MHC class II expression reveals a limited role for B cell antigen presentation in primary and secondary CD4 T cell responses. J Immunol 191:545-50
Wu, Gregory F; Shindler, Kenneth S; Allenspach, Eric J et al. (2011) Limited sufficiency of antigen presentation by dendritic cells in models of central nervous system autoimmunity. J Autoimmun 36:56-64