The Tomer lab is studying the immunogenetic, epigenetic, and environmental mechanisms underlying autoimmune thyroid disease (AITD), and type 1 diabetes (T1D). Both AITD and T1D are among the commonest autoimmune diseases. The prevalence of AITD is estimated to be 5%, and that of type 1 diabetes (T1D) is about 0.4%. Moreover, AITD and T1D frequently occur in the same family and even in the same individual (for a review see Huber, Menconi, Corather, Jacobson, Tomer. Endocrine Reviews 2008; 29: 697-725).
The two major autoimmune thyroid diseases are Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Intriguingly, these two clinically distinct syndromes share common immunopathogenic mechanisms. While the hallmark of GD is thyrotoxicosis (overactive thyroid) and of HT hypothyroidism (underactive thyroid), both are characterized by lymphocytic infiltration of the thyroid and the production of thyroid autoantibodies. T1D is characterized by the formation of islet specific T-cells and autoantibodies and inflammatory destruction of the beta cells leading to hyperglycemia and the associated end-organ complications.
The mechanisms triggering AITD and T1D are still unclear. The epidemiological data point to an interaction between genetic susceptibility and environmental triggers as the key factors leading to the breakdown of tolerance and the development of the disease. Our group is dissecting the mechanisms underlying the development of AITD and T1D and we are targeting these mechanisms in order to develop novel therapies. Our group made several important discoveries including identifying new genes and mechanisms underlying the strong association between type 1 diabetes and autoimmune thyroiditis; demonstrating that CD40 and thyroglobulin are major susceptibility genes for AITD; identifying a unique amino acid variant in the peptide binding pocket of HLA-DR that is key for the development of thyroid autoimmunity; dissecting the epigenetic mechanisms by which polymorphisms in the thyroglobulin and TSHR genes interact with environmental agents (e.g. viruses) to trigger thyroid autoimmunity; demonstrating that the hepatitis C virus can trigger autoimmune thyroiditis by directly infecting thyroid cells; identifying a novel small molecule that can block antigen presentation in autoimmune thyroiditis.
We invite you to explore our lab website to learn more about our research programs.
