Project Summary:
Type 1 diabetes (T1D) develops when the immune system mistakenly destroys the insulin-producing beta cells in the pancreas. A balance normally exists between immune cells that attack and those that protect, but in T1D this balance is lost.
Dr. Grisanti’s focuses on a protein called 4E-BP2, which helps regulate how immune cells function. In a mouse model of T1D, it was shown that removing 4E-BP2 protected mice from developing diabetes. These mice kept more of their beta cells, and their immune cells were less aggressive. They also had fewer harmful, beta-cell destructing T cells and more regulatory T cells—the cells that help calm the immune response.
Dr. Grisanti want to understand why removing this protein changes the immune response. Her goal is to study how T cells behave when 4E-BP2 is missing—whether they become inflammatory “attack” cells or shift toward more protective, regulatory types. She will use single cell RNA sequencing (scRNAseq) to analyze immune cells that infiltrate the pancreas to identify the molecular changes caused by the absence of 4E-BP2. This will allow Dr. Grisanti to pinpoint the pathways that make the immune system less likely to attack beta cells.
By uncovering how 4E-BP2 shapes the immune response, this project may reveal new biomarkers for disease risk and new therapeutic targets to prevent or slow type 1 diabetes. Understanding these mechanisms could eventually support the development of treatments aimed at stopping the immune attack before β-cells are permanently damaged.
