Identification and validation of serum biomarkers for T1D

Early studies have shown that individuals at risk for type-1 diabetes can be identified by using a combination of genetic, metabolic and immunologic markers. However, these currently available biomarkers are not satisfactory because of low accuracy and technical difficulties. Better biomarkers with high accuracy and earlier markers would be of tremendous value for early disease prevention. We have been developing modern technologies to identify serum protein differences between T1D patients and normal controls. Previous studies suggest that serum is the ideal place to look for biomarkers for many human diseases including T1D. Our own studies also suggested that the modern protein technologies coupled with computational techniques should allow the development of new biomarkers.

My advanced postdoctoral training is aimed at identifying and validating biomarkers for T1D. These goals will be accomplished in two phases. In the first phase, I will search for (discover) candidate proteins that have the potential to serve as biomarkers. For this purpose, I will analyze sufficiently large number of T1D patients, autoantibody positive (AbP) and matched autoantibody-negative (AbN) controls by using two protein technologies. The first technique, Luminex bead technology, will allow me to evaluate specific proteins with relevant immunological functions and/or demonstrated implication in autoimmune diseases. This candidate protein approach will be complimented by a proteome-wide (all proteins) search for protein changes among the study groups with a modern protein separation technique known as two-dimensional chromatography coupled to a protein identification technique known as mass spectrometry. In the second phase, I propose to validate the biomarker candidates identified in the discovery phase through analyses of additional samples of patients and controls. More importantly, the candidate biomarkers will be validated through samples from a longitudinal monitoring program, a critical requirement to assess the utility of new biomarkers. Finally, an important aspect of my approach involves the use of combinational power of multiple proteins through modern computational techniques. These approaches represent the most advanced techniques for biomarker discovery and should allow us to identify and validate useful biomarkers for T1D.