MiRNAs as serum biomarkers for T1D

Abstract Prospective cohort studies in individuals at risk for Type diabetes T D have established that diagnosis of the disease occurs at a late stage in the progressive decline in cell function when the majority of cell function has been lost and the possibility for disease prevention is gone Current measures of autoantibodies HLA typing and oral glucose tolerance tests OGTT are able to identify persons with up to an five year risk of developing the disease Thus new biomarkers are urgently needed to improve early risk characterization and to monitor the autoimmune disease process before the complete destruction of cells Our long term goal is to develop new sensitive and specific markers for early accurate prediction of diabetes and to develop strategies by which to screen populations to identify individuals at risk MicroRNAs miRNAs are a recently discovered class of evolutionarily conserved small noncoding RNAs that negatively regulate the expression of protein coding genes Recent studies from our lab and others have indicated that miRNAs control immune cell development function and are involved in cytokine mediated cell apoptosis Furthermore more than of miRNAs are located in human or mouse diabetes Idd loci and there are different expression profiles of miRNAs in the immune cells during T D development and in cells during their apoptosis suggesting the potential involvement of miRNAs in T D development More recently it has been discovered that serum plasma contain large amount of stable miRNAs deriving from various tissues organs This exciting discovery has opened the possibility that cell free circulating miRNAs could represent a surrogate of miRNA expression in diseased tissues and serve as disease biomarkers Using miRNA arrays we recently identified distinct serum miRNA biomarkers related to immune cells and cells for diabetes staging in the nonobese diabetic NOD mice and defined specific miRNA expression profiles in diabetes families The objective here is to identify and confirm specific serum miRNA biomarkers for early T D prediction Our preliminary findings lead to our central hypothesis that miRNAs derived from islets and immune cells during T D development could be detected in the serum and serve a novel class of blood based biomarkers for T D prediction We will test our hypothesis by two Specific Aims In Aim we will further identify and confirm serum miRNA biomarkers for T D using T DGC samples In Aim we will identify and evaluate serum miRNA biomarkers for T D prediction using DPT samples The results from the proposed pioneering studies may enable us to define new stable serum biomarkers miRNAs to predict T D development and may also facilitate the development of new intervention strategies for T D therapy Project Narrative Prospective cohort studies in individuals at risk for Type diabetes T D have established that diagnosis of the disease occurs at a late stage in the progressive decline in cell function when the majority of cell function has been lost and the possibility for disease prevention is gone Current strategies are able to identify persons with up to an five year risk of developing the disease Thus new biomarkers are urgently needed to improve early risk characterization and to monitor the autoimmune disease process before the complete destruction of cells Recent studies from our lab and others have indicated that miRNAs control immune cell development function and are involved in cytokine mediated cell apoptosis Using miRNA arrays we recently identified distinct serum miRNA biomarkers related to immune cells and cells for diabetes staging in the nonobese diabetic NOD mice and defined specific miRNA expression profiles in diabetes families The overall goal of this proposal is to identify and confirm serum miRNA biomarkers for T D prediction an progression using serum samples from T DGC and PDT studies The results from the proposed pioneering studies may enable us to define new stable serum biomarkers miRNAs to predict T D development and may also facilitate the development of new intervention strategies for T D therapy