Sanja Glisic, PhD
Assistant Professor
Department of Pediatrics
8701 Watertown Plank Rd
Milwaukee, WI 53226
Phone: (414) 456-4572
Fax: (414) 456-6663
Email: sglisic@mcw.edu
Education:
PhD, University of Belgrade, Yugoslavia, 1998
Postdoctoral, University of Notre Dame, IN, 2003
Medical College of Wisconsin, WI, 2005
Research Area:
Immunogenetics of T cells in Type 1 Diabetes
The focus of the Glisic Laboratory is to understand the role of T cell subsets in T1D pathogenesis. There are several T cell subsets within T cells and we are looking into regulatory T cells, a T-cell subset that is crucial in immune homeostasis. The role of Tregs in T1D has attracted considerable attention and a few studies have reported decreased regulatory function of Tregs in pediatric subjects with T1D. Despite accumulating data about the dysfunction of Tregs in T1D patients, there is no compelling evidence identifying an underlying cause. Our lab is interested in the mechanism of spontaneous apoptosis of Tregs in human T1D. We believe that through interventions affecting T cells, it is possible to modulate the immune cascade and lead to disease remission. Since the isolation of natural Treg cells is still a subject of many studies, as a unique surface marker for Tregs is not yet found, we are currently combining proteomics with immunogenetics in search for a better Treg marker. Using a specific apoptosis stain combination developed in our lab, we were able to detect increased Treg apoptosis in recent-onset T1D subjects (recruited within first 8 months from the diagnosis) and in multiple autoantibody-positive unaffected subjects, compared to long-standing T1D and T2D subjects. This increased Treg apoptosis was also correlated to decreased Treg function. We are also looking into expression of genes in signaling pathways that could trigger apoptosis of Tregs in T1D subjects, as well as genetic variations and their association with T1D. Expression signatures indicate that Tregs from T1D subjects display a cellular response that leads to decreased activation and increased sensitivity to apoptosis, partially due to deprivation of IL-2 and other cytokines. In addition, unaffected, autoantibody-negative high risk HLA-DQB1 control subjects showed increased Treg apoptosis compared with low-risk HLA-DQB1 control subjects, confirming that the association precedes disease. The association of specific HLA genotypes with Treg apoptosis was also tested, showing significance for HLA DQB1*030, DQB1*0201 and DQB1*0602 alleles.
How long before the onset does Treg apoptosis start? Is increased Tregs apoptosis marker for T1D? Can it serve as a screening tool for detection of prediabetic individuals? Can increased Treg apoptosis help predict existence/cessation of the honeymoon period? Why Tregs apoptosis happens and what is causing their death? Why don’t other T cell subsets die by apoptosis? Studies exploring this phenomenon and answering posed questions are on the way.
Click here for Dr. Glisic's Faculty Collaboration Database profile page, which includes an up to date listing of his publications.