After carefully evaluating the merits, potential pitfalls, concerns and failures of the strategies so far proposed to treat autoimmune diseases, it was concluded that recombinant antibody and dendritic cell-based approaches would be clinically translatable modalities with the greatest likelihood of success during treatment, combined with the least concern of deleterious side effects. Importantly, the investigators collaborating in this proposal have themselves, or are collaborating with others at the University of Pittsburgh who have exceptional expertise in these approaches. This application will provide further insights into the basic mechanisms of action of the proposed approaches, in itself a compelling rationale for their selection and evaluation. To better organize these studies, it was also concluded that an Autoimmunity Center of Excellence may represent the most appropriate """"""""umbrella"""""""" under which to consolidate the efforts of the interested clinicians and scientists of the University of Pittsburgh. The complexity of studying and developing new therapeutic approaches to treating autoimmune diseases requires a modern, multidisciplinary research climate. The synchronization of both the expertise and the technology available among the investigators within this university who are interested in the same scientific area, i.e., autoimmunity, is necessary in order to maximize the use of all of the resources in the most cost effective and academically efficient manner. Moreover the University of Pittsburgh will greatly benefit from a forum specifically dedicated to the study of autoimmunity, where both junior and established investigators within different departments and institutions, and with interdisciplinary expertise, can be drawn together with interested clinicians so that bench-to-bedside transfer can be fostered more efficiently. In order to encourage young researchers to devote their careers to the study of autoimmune ailments, especially those that affect children, it is here proposed to build an Autoimmune Center of Excellence with the specific belief that fostering of this type of career is easier within a scientifically challenging atmosphere of collegiality and intellectual discourse. Finally, having an Autoimmunity Center of Excellence in Pittsburgh entirely dedicated to a single philosophical and scientific goal: """"""""understanding, preventing and eventually curing autoimmune diseases"""""""" will allow the creation of new scientific leads that will form the basis for more promising clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI056374-02
Application #
6803537
Study Section
Special Emphasis Panel (ZAI1-CL-I (M2))
Program Officer
Johnson, David R
Project Start
2003-09-30
Project End
2008-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$705,866
Indirect Cost
Name
Children's Hosp Pittsburgh/Upmc Health Sys
Department
Type
DUNS #
044304145
City
Pittsburgh
State
PA
Country
United States
Zip Code
15224
Whitener, Robert L; Gallo Knight, Lisa; Li, Jianwei et al. (2017) The Type 1 Diabetes-Resistance Locus Idd22 Controls Trafficking of Autoreactive CTLs into the Pancreatic Islets of NOD Mice. J Immunol 199:3991-4000
Chen, Jing; Mathews, Clayton E (2014) Use of chemical probes to detect mitochondrial ROS by flow cytometry and spectrofluorometry. Methods Enzymol 542:223-41
Broniowska, Katarzyna A; Mathews, Clayton E; Corbett, John A (2013) Do ?-cells generate peroxynitrite in response to cytokine treatment? J Biol Chem 288:36567-78
Kachapati, Kritika; Adams, David E; Wu, Yuehong et al. (2012) The B10 Idd9.3 locus mediates accumulation of functionally superior CD137(+) regulatory T cells in the nonobese diabetic type 1 diabetes model. J Immunol 189:5001-15
Ize-Ludlow, Diego; Lightfoot, Yaima L; Parker, Matthew et al. (2011) Progressive erosion of ?-cell function precedes the onset of hyperglycemia in the NOD mouse model of type 1 diabetes. Diabetes 60:2086-91
Chen, Jing; Gusdon, Aaron M; Piganelli, Jon et al. (2011) mt-Nd2(a) Modifies resistance against autoimmune type 1 diabetes in NOD mice at the level of the pancreatic ?-cell. Diabetes 60:355-9
Thayer, Terri C; Delano, Matthew; Liu, Chao et al. (2011) Superoxide production by macrophages and T cells is critical for the induction of autoreactivity and type 1 diabetes. Diabetes 60:2144-51
Wang, Wenfang; Guo, Ying; Xu, Ming et al. (2011) Development of diabetes in lean Ncb5or-null mice is associated with manifestations of endoplasmic reticulum and oxidative stress in beta cells. Biochim Biophys Acta 1812:1532-41
Chen, Jing; Grieshaber, Scott; Mathews, Clayton E (2011) Methods to assess beta cell death mediated by cytotoxic T lymphocytes. J Vis Exp :
Thayer, Terri C; Wilson, S Brian; Mathews, Clayton E (2010) Use of nonobese diabetic mice to understand human type 1 diabetes. Endocrinol Metab Clin North Am 39:541-61

Showing the most recent 10 out of 46 publications