Estefania Quesada-Masachs, M.D., Ph.D

What if a person’s insulin-producing beta cells are orchestrating their own demise?

Funded: January 2022
Funded By: The generosity of Barbara Donnell and Denny Sanford

Type 1 diabetes (T1D) is a chronic disease that results from the autoimmune destruction of insulin-producing beta cells. My hypothesis for this SPARK project is that beta cells may directly present self-antigens to autoreactive CD4+ T cells, and hence, I am now investigating whether pancreatic beta cells can directly communicate to CD4+ T cells and the effects of this cross communication.

Using an innovative platform with 3D human islet microtissues, I co-cultured those islet spheroids with human CD4 T cells from HLA matched donors and monitored changes in islet shape and size, and overall CD4 T cell infiltration. I also studied functional changes with the GSIS (glucose stimulated insulin secretion test). Additionally, I am obtaining high-resolution images with confocal LSM 780 to precisely quantify CD4 T cell infiltration and the expression and colocalization of markers of interest. The high quality of the stainings allows us to precisely locate the infiltrating T cells and locate and quantify the expression of our markers of interest. Using SPARK funds, I have improved our methods to process the islet spheroids after staining them, and now I can preserve their 3D structure, create 3D isosurfacing of the whole structure using Imaris, and perform 3D image analysis. I anticipate having preliminary data very soon.

SPARKing Impact: Determining the mechanism behind the destruction of insulin-producing cells has the potential to radically change the future approach to novel treatments for type 1 diabetes.