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Research interests

The long-term goal of the laboratory is to understand antigen presentation, both at the cellular and biochemical level, and to correlate antigen presentation events to the response of CD4 T lymphocytes. Our current focus is entirely on autoimmune diabetes, examining the non-obese diabetic (NOD) mouse. We combine biochemical and biological parameters related to antigen selection, recognition and processing by antigen presenting cells (APC) and T cell selection. Our goals are to identify the initial cellular and molecular events that initiate and perpetuate this autoimmune disease.

Our investigations focus mostly on examining pancreatic islets at the early start of the diabetic process- we do this by isolating islets and examining the resident myeloid cells, the endothelial and mesenchymal cells, as well as the first entering T cells. Islets are mini-organs where the initiating events and interactions among cells can be examined in great detail. Cells can be isolated and examined by different functional and gene expression signatures. In the NOD mouse, diabetogenesis is already evident by the third week of life. Islets normally have a population of macrophages that is distinct from those that inhabit the exocrine pancreas.These macrophages have been extensively analyzed by us since they are vital for islet homeostasis and in the case of NOD, in the initiation of diabetes. The autoimmune process starts in islets with the entrance of CD4+ T cells and a small number of dendritic cells many of which are DC1 expressing the XCR1 protein. Many of the early T cells react to insulin peptides. We have extensively examined the insulin reactive T cells and characterized the insulin epitopes that are recognized by them. We examine how insulin peptides are presented to these insulin T cells, the role of the unique MHC class II molecules of the NOD [I-Ag7] and the various cellular interactions.

We are always looking for talented graduate students and post-docs interested in studying the nuances of autoimmune diabetes disease initiation


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