The Autoimmunity Center of Excellence at the Albert Einstein College of Medicine will encompass research projects, an infrastructure for clinical trials and an administrative core. This Center reflects an interdisciplinary approach to autoimmune disease. It involves a collaboration of clinicians and basic scientists that is focused on translational studies to develop new therapeutic strategies. The research component will be directed by Betty Diamond and includes three research projects. Each project has the goal of developing new targets for therapy in autoimmune disease. The first project (PI: Anne Davidson) is a study of the effects of statins alone or in conjunction with CTLA-4Ig in the NZB/W mouse model of lupus. This project will include a study of the effect of statins on peripheral blood mononuclear cells of lupus patients. The second project (PI: Betty Diamond) is a study of the effect of CD22 over-expression on B cell development and on autoantibody production in murine models of SLE and includes a study of a CD22 polymorphism reported to associate with lupus. Overall it will explore whether inhibition of CD22 represents a useful therapeutic strategy. The third project (PI: Stanley Nathenson) is a biophysical study of the polymorphism of murine two microglobulin that is required for the expression of diabetes in NOD mice. This study will provide a comprehensive biophysical characterization of the features of TCR/MHC-peptide complexes that are directly relevant to eliciting diabetes. These studies promise to provide the atomic and molecular mechanisms responsible for disease development and thus may lead to novel strategies for the design of therapeutics that will limit disease-associated T cell reactivity. A clinical infrastructure is described (Clinical Director: Cynthia Aranow) that is capable of performing clinical trials in autoimmune rheumatic diseases, type 1 diabetes, autoimmune hematologic diseases, and inflammatory bowel disease. In addition, there are proposals for a clinical trial of DNase I in serologically active, clinically inactive lupus and for a trial of statin therapy as a steroid sparing agent in rheumatoid arthritis. Finally, the Center will include an administrative core for coordination and implementation of Center activities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
7U19AI056362-06
Application #
7254745
Study Section
Special Emphasis Panel (ZAI1-CL-I (M2))
Program Officer
Johnson, David R
Project Start
2003-09-30
Project End
2010-03-31
Budget Start
2007-04-01
Budget End
2010-03-31
Support Year
6
Fiscal Year
2007
Total Cost
$1
Indirect Cost
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030
Aranow, Cynthia (2011) Vitamin D and the immune system. J Investig Med 59:881-6
Wang, Ying-Hua; Yan, Yi; Rice, Jeffrey S et al. (2011) Enforced expression of the apoptosis inhibitor Bcl-2 ablates tolerance induction in DNA-reactive B cells through a novel mechanism. J Autoimmun 37:18-27
Ben-Zvi, Ilan; Aranow, Cynthia; Mackay, Meggan et al. (2010) The impact of vitamin D on dendritic cell function in patients with systemic lupus erythematosus. PLoS One 5:e9193
Jacobi, Annett M; Huang, Weiqing; Wang, Tao et al. (2010) Effect of long-term belimumab treatment on B cells in systemic lupus erythematosus: extension of a phase II, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum 62:201-10
Burstein, Sumner H; Zurier, Robert B (2009) Cannabinoids, endocannabinoids, and related analogs in inflammation. AAPS J 11:109-19
Levesque, Marc C; St Clair, E William (2008) B cell-directed therapies for autoimmune disease and correlates of disease response and relapse. J Allergy Clin Immunol 121:13-21;quiz 22-3
Kahn, Philip; Ramanujam, Meera; Bethunaickan, Ramalingam et al. (2008) Prevention of murine antiphospholipid syndrome by BAFF blockade. Arthritis Rheum 58:2824-34
Zhang, Jie; Jacobi, Annett M; Mackay, Meggan et al. (2008) Identification of DNA-reactive B cells in patients with systemic lupus erythematosus. J Immunol Methods 338:79-84
Stebulis, Judith A; Johnson, David R; Rossetti, Ronald G et al. (2008) Ajulemic acid, a synthetic cannabinoid acid, induces an antiinflammatory profile of eicosanoids in human synovial cells. Life Sci 83:666-70
Tiller, Thomas; Tsuiji, Makoto; Yurasov, Sergey et al. (2007) Autoreactivity in human IgG+ memory B cells. Immunity 26:205-13

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