Karoliina Hirvonen from Riitta Lahesmaa lab defended her PhD thesis “Proteomics Insights into Type 1 Diabetes Development – Investigating Changes in Serum Proteome and the Role of Persistent Enterovirus Infection” on Thursday the 22nd of May 2025. Her opponent was Professor Jochen Schwenk from Science for Life Laboratory, KTH Royal Institute of Technology, Sweden.

Warmest congratulations Karoliina!

Summary of the Dissertation:

Type 1 diabetes is a chronic disease that leads to gradual destruction of insulin producing beta cells in the pancreas. By the time of diagnosis, most of the beta cells have already been destroyed. There is a need to improve our understanding of the molecular events governing the disease, from early signs to diagnosis and beyond. Identifying molecules that change at the various stages of disease could improve clinical decisions, assist in monitoring, and help classify individuals into subgroups.

In the work presented in this dissertation, mass spectrometry (MS)-based proteomics methods were employed to investigate type 1 diabetes-associated changes in serum protein levels and to explore how persistent enterovirus infection, which have been linked to the disease, alters protein expression and secretion in pancreatic ductal cells (PANC-1). Longitudinal proteomics analysis of pre-onset serum samples from children who developed type 1 diabetes at a young age revealed decreased levels of apolipoprotein C1 (APOC1) early in the disease, which remained lower until diagnosis. Targeted MS analysis of serum samples from newly diagnosed (ND) youth and unaffected family members (UFMs) further identified lower serum APOC1 levels in ND youth and revealed 12 additional proteins with differing serum levels between the two groups. Eleven proteins were also found to be associated with fasting C-peptide/glucose ratios, which served as a measure of functional beta cell mass. A validation study in a second cohort confirmed serum level differences for 10 proteins, including APOC1, between ND and UFMs and replicated negative association with the C-peptide/glucose ratios for three proteins. Persistent enterovirus infection in PANC-1 cells, using two different coxsackievirus B1 (CVB1) strains, led to significant changes in protein expression and secretion, especially affecting mitochondrial functions and the regulated secretory pathway. Notably, the two CVB1 strains also showed different effects on proteins related to the antiviral immune response. Several of the significantly altered proteins in the CVB1 models were also detected in the serum samples.

This research identified a set of proteins linked to the progression of type 1 diabetes and those modulated during persistent CVB1 infection. While a specific CVB1 signature was not found in the serum analyses, a group of overlapping proteins identified in the studies may contribute to the CVB1 infection signature.