NUTRAGE - ITB Segrate

Dysregulation of NOTCH signaling plays a fundamental role in aging, neurodegeneration, inflammatory diseases, and cerebrovascular dementia. We propose to identify the role of transmembrane proteins (TMEM) in NOTCH signaling. We will use stem cells derived from patients with autoimmune diseases or patient-derived iPSCs derived from patients with neurodegenerative diseases to generate 3D organoid cocultures for single-cell transcriptome studies. Objectives: 1) define the role of TMEM proteins in NOTCH signaling and epigenomic reprogramming; 2) analyze the interconnections of TMEM proteins with lipid rafts and intracellular and extracellular glycoproteins, which are essential for correct protein folding, vesicular trafficking, and apoptosis. Expected results: 1) identify potential biomarkers and target genes for the design of new therapies; 2) investigate cell therapies in neurodegenerative or autoimmunity-associated diseases.