UB pharmacy researcher makes diabetes breakthrough in $3.5 million funded study

BUFFALO, N.Y. ­­— Jun Qu, professor of pharmaceutical sciences at the University at Buffalo, and researchers in his lab have made a significant breakthrough in diagnosing and classifying Type 1 diabetes. They developed an advanced technology that can detect and measure previously undetectable protein molecules at extremely low concentrations in the blood.

“Classifying, diagnosing and staging diabetes is crucial for disease management, but until now we lacked the tools to do so,” says Qu, the principal investigator (PI) of a four-year, $3.5 million study funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

The other PI is Weijun Qian of Pacific Northwest National Laboratory in Richmond, Wash., an internationally renowned expert in diabetes and biomarker techniques.

“This new technique provides a much more accurate and specific picture of how insulin production is changing and how the functions of beta (β) cells in the pancreas become compromised at each stage of diabetes,” Qu says. “It could help manage patients in the early stages of the disease and potentially slow down progression to full-blown diabetes.”

An article detailing their discovery was the cover story in a recent issue of Analytical Chemistry, a top journal of analytical science. Primary authors are Qingqing Shen, a former UB doctoral student who now works at Bristol Myers Squibb, and Wang Cao, a UB graduate student in pharmaceutical sciences in the School of Pharmacy and Pharmaceutical Sciences.

The study has drawn strong interest from the diabetes research community for its potential to identify novel diagnostic tools. Qu and Qian recently presented their findings at the 2025 American Diabetes Association conference in Chicago; the Association for Mass Spectrometry & Advances in the Clinical Lab in Montreal, Canada; and the European Bioanalysis Forum in Barcelona, Spain.

Qu notes that the technology may also be applied to other diseases in which different forms of key proteins, known as proteoforms, carry important biological information.

‘Holy grail’ in the field

To achieve this breakthrough, Qu and his team devised an ultra-sensitive analytical method based on liquid chromatography–mass spectrometry (LC-MS), using a new state-of-the art mass spectrometer housed at the UB Proteomics and Bioanalysis Core in the University at Buffalo Center of Excellence in Bioinformatics and Life Sciences (CBLS). The instrument, acquired recently from Thermo Fisher Scientific, is the second high-end mass spectrometer obtained by Qu’s lab in the past two years.

With this technology, they were able to measure serum samples of 80 adolescents with molecular-level precision. They focused on different forms of proinsulin, the precursor molecule produced by the pancreas that is processed into insulin and C-peptide in circulation.

“For decades, scientists have recognized the importance of measuring circulating proinsulin and its intermediate forms to more effectively characterize diabetes,” Qu says. “No one, however, had succeeded because of two major challenges: These molecules exist at extremely low, part-per-trillion levels in the blood and the different forms of proinsulin differ by only a few amino acids, making them very difficult to distinguish.”

“It has been almost a ‘holy grail’ in this field,” he adds. “Everyone knew these measurements were important, but nobody could make them accurately, until now.”

The novel technique developed by Qu’s team incorporated three technical advances from his lab: an antibody-cocktail enrichment to capture proinsulin form, a technique to sharpen the signals,  and a trapping nano-LC strategy that operates at an extremely low flow rate. Qu points out that the flow is so precisely controlled and so low that even if the system ran continuously for an entire year, it would consume less than 5 ounces of liquid while achieving ultra-high sensitivity, precision and robustness.

“It enables us to accurately determine the levels of these insulin prohormones with amazing sensitivity and specificity,” he says.

Finding what current proinsulin tests have missed

Using their new technique, the team successfully measured three main proinsulin forms and C-peptide in serum from the young participants, who were divided into those at risk for Type 1 diabetes, those recently diagnosed with Type 1 diabetes and their respective healthy controls.

The technique allowed the researchers to see clear differences between healthy and diabetic individuals that standard proinsulin tests missed due to limited sensitivity and specificity.

“Accurately quantifying all three forms gives us a wealth of information about β-cell loss and helps us stage and phenotype the disease,” Qu says. “Nobody has been able to achieve it before.”

Now being used in longitudinal clinical studies of diabetes patients, the technology is already generating new insights.

Better diagnostics and disease management

Qu says the research team is in the patent stage and hopes to get it out in the field as soon as possible.

“This process can help in the research and diagnosis not only of Type 1 diabetes but also Type 2 or other diseases involving β-cell dysfunction,” Qu says. “In the future, we think that the knowledge acquired by this method will guide better strategies to manage diabetes before and after the onset of the disease. If we can delay or even halt the disease’s progression, we significantly improve patients’ quality of life.”

Other research partners for this study included Tai-Tu Lin, a biomedical scientist at Pacific Northwest National Laboratory; Gabriela Scavacini de Freitas Monaco, a resident in the Department of Pediatrics at Indiana University School of Medicine; Ming Zhang, a research scientist in UB’s Pharmaceutical Sciences Department; Scott Peterman and Cornelia Boeser of Thermo Fisher Scientific; and Carmella Evans-Molina and Emily K. Sims from Indiana University School of Medicine.