Samia J. Khoury
My laboratory is interested in multiple sclerosis and its animal model EAE. Multiple sclerosis (MS) is an immune mediated disorder of the central nervous system. T lymphocytes are thought to play a central role in the initiation and potentially in the propagation of this disease. In the EAE model we are investigating methods for inducing tolerance and the basic immunopathogenic mechanisms leading to neurologic injury in this model. We have focused on costimulatory signal blockade in EAE including both positive and negative pathways. We are interested in costimulatory signals required for T cell activation, and their role in EAE and MS. Another area of interest is “signal 3” i.e. signals delivered from the APC to the T cell that determine its differentiation into an effector cell. Notch is an example of a signal 3 mediator that can promote TH1, TH2, or TH17 cell differentiation through its ligands expressed on APCs.
Current immunomodulatory therapies partially alter the disease course of MS typically by decreasing relapses, however the secondary progressive form and chronic disease remains resistant to such treatments. In several models of experimental demyelination, it has been clearly demonstrated that progenitor cells of the adult mouse subventricular zone (SVZ) proliferate, migrate, and differentiate into oligodendrocytes. However, clearly remyelination and neuro-regeneration do not occur to a sufficient extent in MS or EAE. We are investigating the interaction between the inflammatory milieu and endogenous neural stem and progenitor cells with the hope of developing therapies that promote remyelination and repair.
Kivisäkk P, Imitola J, Rasmussen S, Elyaman W, Zhu B, Ransohoff RM, Khoury SJ. Localizing central nervous system immune surveillance: Meningeal antigen-presenting cells activate T cells during experimental autoimmune encephalomyelitis. Ann Neurol. 2009 Apr;65(4):457-469.
Elyaman W, Bradshaw EM, Uyttenhove C, Dardalhon V, Awasthi A, Imitola J, Bettelli E, Oukka M, van Snick J, Renauld JC, Kuchroo VK, Khoury SJ. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci USA. 2009 Aug 4;106(31):12885-12890. PMC2722314
Starossom SC, Imitola J, Wang Y, Cao L, Khoury SJ. Subventricular Zone Microglia Transcriptional Networks. Brain Behav Immun.2011 Nov. NIHMSID252647
Imitola J, Côté D, Rasmussen S, Xie XS, Liu Y, Chitnis T, Sidman RL, Lin CP, Khoury SJ. Multimodal coherent anti-stokes raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice. J Biomed Optics. 2011 Feb; 16(2):021109/1-021109/11
Rasmussen S, Imitola I, Ayuso-Sacido A, Wang Y, Starossom S, Kivisäkk P, Zhu B, Meyer M, Bronson RT, Manuel Garcia-Verdugo J, Khoury SJ. Reversible Neural Stem Cell Niche Dysfunction In A Model Of Multiple Sclerosis. Ann Neurol. 2011 May;69 (5):878–891
Last Update: 1/6/2014