The Molecular Pathology and Immunology Core of the University of Florida currently assists multiple investigators participating in Projects aimed at an improved understanding of the pathogenesis of type 1 diabetes, as well as the development of agents capable of reversing and/or preventing the disease. Specifically, the Core supports these investigations by performing pathological and immunological analyses that characterize the host's immune system and cell/tissue response, including those involving treatments proposed or currently used in experimental and preclinical studies. This goal has and will continue to be accomplished by performance of three specific aims: 1) Determine tissue morphology in the context of histopathology in order to evaluate treatment effects with respect to administration site, dose, and treatment duration. 2) Determine the potential beneficial effects of treatments in murine models of diabetes;with assessment of the pancreas as well other organs related to type 1 diabetes. 3) Perform immunologic evaluations in animal models and human subjects that characterize aspects related to the humoral and cellular immune response, as well as providing genetic susceptibility to type 1 diabetes. The morphological studies are vital in order to evaluate whether a given Project's intervention successfully ameliorates the pro- inflammatory environment within the pancreas, lymph node, spleen, and other organs and to determine the extent to which any intervention induces acute inflammation or cytotoxicity. Centralization of the morphological studies, and standardization of the histopathological and toxicological determinants, enables rigorous assessment of cellular responses. Procedures include standard histology on paraffin and frozen materials, special stains, histochemistry, immunohistochemistry, and immunofluorescence. In terms of analysis of human samples, the Core laboratory will build upon more that two decades of experience in terms of evaluating for the presence of autoantibodies in serum of patients with or at increased-risk of type 1 diabetes, as well as determining the genetic susceptibility for the disease by performance of HLA typing. In addition to providing a critical element for assurance of therapeutic safety and improved mechanistic understanding, the Core should provide information that will enhance the feasibility and efficacy of preclinical trials to prevent or reverse type 1 diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI042288-13
Application #
8131064
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
13
Fiscal Year
2010
Total Cost
$159,932
Indirect Cost
Name
University of Florida
Department
Type
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Perry, Daniel J; Wasserfall, Clive H; Oram, Richard A et al. (2018) Application of a Genetic Risk Score to Racially Diverse Type 1 Diabetes Populations Demonstrates the Need for Diversity in Risk-Modeling. Sci Rep 8:4529
Chen, Yi-Guang; Mathews, Clayton E; Driver, John P (2018) The Role of NOD Mice in Type 1 Diabetes Research: Lessons from the Past and Recommendations for the Future. Front Endocrinol (Lausanne) 9:51
Kusmartseva, Irina; Beery, Maria; Philips, Tiffany et al. (2018) Hospital time prior to death and pancreas histopathology: implications for future studies. Diabetologia 61:954-958
Hu, Ronghua; Xia, Chang-Qing; Butfiloski, Edward et al. (2018) Effect of high glucose on cytokine production by human peripheral blood immune cells and type I interferon signaling in monocytes: Implications for the role of hyperglycemia in the diabetes inflammatory process and host defense against infection. Clin Immunol 195:139-148
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Seay, Howard R; Putnam, Amy L; Cserny, Judit et al. (2017) Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy. Mol Ther Methods Clin Dev 4:178-191
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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