Qu receives NIH grant to develop targeted mass spectrometry assays as markers in monitoring Type 1 diabetes

Type 1 diabetes (T1D) results from the autoimmune-mediated loss of pancreatic β-cells. It is challenging to monitor disease progression and the efficacy of clinical interventions. A critical need remains for highly reliable assays that quantify proteins or peptide hormones (e.g., insulin, glucagon) and their specific isoforms (or proteoforms) as markers of endocrine and exocrine function. These assays will play an important role in facilitating effective monitoring of disease progression or efficacy of novel clinical interventions prior to or following the onset of T1D.

Most current clinical assays depend on the use of antibodies or other affinity reagents almost exclusively. However, the exact specificity of affinity reagents is often questionable or difficult to characterize. Targeted mass spectrometry (MS) presents a promising alternative to immunoassays. The overall objective of this study is to develop advanced, proteoform-specific, and multiplex targeted MS assays for a list of protein/peptide analytes of significance in T1D and other markers of interest to the T1D research community.

This study will establish highly reliable and easy-to-transfer multiplex targeted MS assays for many difficult to measure T1D markers. These assays are expected to make a significant contribution to the monitoring of pancreatic endocrine/exocrine functions, the disease progression, as well as the efficacy of clinical interventions in T1D research.

The study will be conducted through the collaborative efforts of two independent targeted MS labs and through a multi-lab assay validation effort. Qu and Wei-Jun Qian, PhD, senior staff scientist, Pacific Northwest National Laboratory (PNNL), are both principal investigators on the grant. Qu partnered with PNNL which is renowned for protein characterization techniques and the study of diabetes.

“Despite many years of rigorous research into T1D, we have yet to achieve a comprehensive understanding of the disease's mechanism, nor its proper diagnosis, phenotyping, and staging,” says Qu. “A significant barrier has been the lack of a precise analytical tool to quantitatively and specifically characterize the appropriate forms of T1D-related biomarkers. We are confident that our proposed work will fill this critical gap, potentially revolutionizing the investigative and therapeutic approaches to T1D.”