""""""""The development of TID relies on interrelationships between cells of the immune system (e.g., DC, Teff, Treg), genes imparting susceptibility or resistance to the disease, and certain cytokines that appear key to the process underlying the autoimmune destruction of insulin producing pancreatic p cells."""""""" Variations on such a statement are common to most descriptions of TID to the point of serving as a central dogma for the pathogenesis of this disorder. While a broad body of evidence certainly exists to support this notion (and we ourselves believe it true), the exact mechanisms by which autoimmune (3 cell destruction is facilitated remain unclear. In addition, the relative contributions of each facet (i.e., cells, genes, cytokines) to the process remain, to a large extent, unknown. This forms a major void for attempts seeking to prevent and/or reverse the disease, as well as to identify improved biomarkers of disease progression &therapeutic efficacy. For these reasons, we deem it essential to perform the proposed research . Within this Specific Aims section of the POI overview, we identify our overall goals as well as the expected mechanistic / experimental outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI042288-15A1
Application #
8566443
Study Section
Special Emphasis Panel (ZAI1-PA-I (M1))
Project Start
Project End
Budget Start
2013-05-10
Budget End
2014-04-30
Support Year
15
Fiscal Year
2013
Total Cost
$404,897
Indirect Cost
$133,154
Name
University of Florida
Department
Type
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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Wasserfall, Clive; Nick, Harry S; Campbell-Thompson, Martha et al. (2017) Persistence of Pancreatic Insulin mRNA Expression and Proinsulin Protein in Type 1 Diabetes Pancreata. Cell Metab 26:568-575.e3
Li, Xia; Campbell-Thompson, Martha; Wasserfall, Clive H et al. (2017) Serum Trypsinogen Levels in Type 1 Diabetes. Diabetes Care 40:577-582
Chen, Jing; Chernatynskaya, Anna V; Li, Jian-Wei et al. (2017) T cells display mitochondria hyperpolarization in human type 1 diabetes. Sci Rep 7:10835

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