Projects

The laboratory of Dr. Tomer studies the mechanisms leading to the development of autoimmune thyroiditis and diabetes. Current projects include:

1) Genetic and epigenetic studies in thyroid autoimmunity. The laboratory discovered that the presence of arginine at position 74 of the peptide binding groove of HLA-DR is critical for disease susceptibility. In collaboration with Roman Osman, PhD, Professor of Structural and Chemical Biology and his team, they identified a specific HLA-DR pocket structure that is associated with thyroid autoimmunity.

The group is now analyzing which immunogenic peptides can bind to these pockets and induce thyroid autoimmunity, since blocking these peptides from binding to the DR pockets can be used as a novel therapeutic approach. Dr. Tomer’s group also identified several non-MHC genetic polymorphisms that are associated with thyroid autoimmunity including variants in the CD40 and thyroglobulin genes. Current studies focus on the genetic and epigenetic mechanisms, by which these variants contribute to disease. The group is using tissue cultures to examine the effects of genetic variants on gene regulation and splicing, as well as transgenic and chimeric mouse models.

2) Genetic analysis of autoimmune (type 1) diabetes and thyroiditis. The laboratory is analyzing genes that confer shared susceptibility to the development of type 1 diabetes and autoimmune thyroiditis in the same individual. The lab has shown that the CTLA-4 and FOXP3 genes play a major role in this shared susceptibility and they are currently studying the mechanisms by which these genes predispose to both diseases. In addition the group is mapping additional genes conferring this shared susceptibility.

3) Environmental factors and thyroid autoimmunity. It is well known that certain infections, specifically hepatitis C, are associated with thyroid autoimmunity. In addition, interferon alpha therapy of hepatitis C can cause thyroiditis in a significant percentage of patients. Using tissue cultures and mouse models Dr. Tomer’s laboratory is studying the mechanisms by which hepatitis C infection, and interferon alpha therapy cause thyroiditis.