A. M. Rostami, MD, PhD

Contact Dr. Rostami

900 Walnut St.

Philadelphia, PA 19107

(215) 955-1234
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What is Etiology and Pathogenesis of Multiple Sclerosis?

Multiple Sclerosis is an autoimmune disease of the central nervous system that affects over 400,000 Americans and over 2 million worldwide. My research focuses on the pathogenesis of multiple sclerosis using the animal model of this disease, experimental autoimmune encephalomyelitis (EAE). At the present, we are focusing on three main areas:

1) The role of IL-12/IL-17/IL-23 axis in the pathogenesis of EAE and multiple sclerosis. Specifically, studies will examine IL-12/IL-17/IL-23 produced by antigen presenting cells (APC) from the periphery (macrophages and dendritic cells) and from the central nervous system (CNS) microglia in EAE. In addition to a better understanding of the pathogenesis of inflammatory demyelination, the information derived from this study will be helpful if these cytokines are to be considered as targets for therapy in MS.

2) The effect of the Bowman-Birk protease inhibitor on the course of EAE. This study has the potential to provide a novel, safe, and effective therapy for multiple sclerosis

3) Mechanisms of intravenous tolerance in EAE. This study will elucidate the mechanisms by which intravenous myelin antigens induce tolerance and suppress clinical disease in EAE. This study will provide a novel method for analyzing the migration and functional status of infiltrating cells in the CNS, in particular, and in target organs of other autoimmune diseases. It has the potential as a possible therapy for autoimmune diseases.

I hope that my findings will be used to better understand the pathogenesis of demyelination in multiple sclerosis and pave the way for designs of new therapies for this disease.

Publications

Most recent Peer-reviewed Publications

1. Intravenous transfer of apoptotic cell-treated dendritic cells leads to immune tolerance by blocking Th17 cell activity
2. Immune tolerance induced by intravenous transfer of immature dendritic cells via up-regulating numbers of suppressive IL-10+ IFN-γ+-producing CD4+ T cells
3. Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination
4. Generation of large numbers of highly purified dendritic cells from bone marrow progenitor cells after co-culture with syngeneic murine splenocytes
5. Independent and interdependent immunoregulatory effects of IL-27, IFN-β, and IL-10 in the suppression of human Th17 cells and murine experimental autoimmune encephalomyelitis
6. Low dose zymosan ameliorates both chronic and relapsing experimental autoimmune encephalomyelitis
7. Role of serine proteases in inflammation: Bowman-Birk protease inhibitor (BBI) as a potential therapy for autoimmune diseases
8. Accelerated and enhanced effect of CCR5-transduced bone marrow neural stem cells on autoimmune encephalomyelitis
9. TCR stimulation upregulates MS4a4B expression through induction of AP-1 transcription factor during T cell activation
10. CNS-specific therapy for ongoing EAE by silencing IL-17 pathway in astrocytes
11. Intravenous tolerance effectively overcomes enhanced pro-inflammatory responses and experimental autoimmune encephalomyelitis severity in the absence of IL-12 receptor signaling
12. IL-10 deficiency blocks the ability of LPS to regulate expression of tolerance-related molecules on dendritic cells
13. Interleukin-10 plays a crucial role in suppression of experimental autoimmune encephalomyelitis by Bowman-Birk inhibitor
14. Bowman-Birk inhibitor attenuates experimental autoimmune encephalomyelitis by delaying infiltration of inflammatory cells into the CNS
15. Generation of immunogenic and tolerogenic clinical-grade dendritic cells
16. IL-9 is important for T-cell activation and differentiation in autoimmune inflammation of the central nervous system
17. Kit (W-sh) mice develop earlier and more severe experimental autoimmune encephalomyelitis due to absence of immune suppression
18. The encephalitogenicity of TH 17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF
19. 3G11 expression in CD4+ T cell-mediated autoimmunity and immune tolerance
20. Oral resveratrol reduces neuronal damage in a model of multiple sclerosis

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