The ASPIRE Path in Molecular Medicine

My research will focus on the role of anti-insulin B cells (AIBCs) in Type 1 diabetes (T1D). Specifically, I will work to characterize the B cell receptor (BCR) of monoclonal AIBC hybridoma lines developed from pre-symptomatic insulin autoantibody positive (IAA+) and negative (IAA-) T1D donors not previously treated with insulin. The goal of my research is to identify possible AIBC biomarkers that could allow for earlier diagnosis of T1D. Approximately 90% of beta cell function is depleted when patients present with T1D symptoms. Therefore, earlier diagnosis may benefit therapeutic intervention in disease prevention and improve clinical trial development by better characterizing disease progression. I plan to amplify, clone and sequence BCRs from our T1D hybridoma lines to identify BCR mutations and characterize the insulin-binding regions of the receptors. I will also perform functional assays such as enzyme-linked immunosorbent assays (ELISA) and biolayer interferometry (BLI) to probe BCR insulin-binding affinity/avidity, specificity and kinetics. I hope to implement LIBRAseq, Linking B-cell Receptor to Antigen specificity through sequencing, to determine the phenotype of these AIBCs. A better understanding of the role of BCR mutation in insulin binding may aid in the identification of sophisticated T1D biomarkers.