Seminario Translational bottom-up proteomics in the study of diabetes and endocrine tumors

Bottom-up proteomics has emerged as a useful tool for investigating endocrine diseases, providing comprehensive protein identification and offering high resolution insight into protein networks, metabolic pathways, and stress response programs in human tissues. In pancreatic islets, shotgun proteomics and acetylome profiling revealed how pro inflammatory cytokines disrupt β cell function by altering metabolic enzymes, cytoskeletal components, immune response mediators, and mitochondrial regulators. Our analyses also showed that therapeutic agents such as metformin can partially counteract cytokine induced dysfunction by modulating oxidative stress defenses, mTOR signaling, and protein epsilon-lysine acetylation. In endocrine tumors, proteomic profiling of atypical parathyroid tumors uncovered a distinct signature characterized by lipid metabolism rewiring, impaired mevalonate cholesterol flux, proteotoxic stress, and non-canonical immunosuppression. Altered ephrin A signaling was also observed as well as a nutrient restricted T cell metabolism further suggested a stressed microenvironment. Together, these studies illustrate how bottom-up proteomics advances the clinical investigation of diabetes and endocrine tumors, that enable the identification of biomarkers and pathways with diagnostic and therapeutic relevance.