Dr. Seetharam’s research interest is to investigate the molecular mechanisms of Graves’ disease (GD). GD is an autoimmune disorder of the thyroid gland characterized by hyperthyroidism and is caused by stimulatory antibodies to thyrotropin receptor (TSHR). Although the GD is mediated primarily by antibodies, the generation of antibodies requires T cell help. Naïve CD4+ T cells, after encounter with an antigen, functionally differentiate into Th1, Th2 or Th17 cells.
Cytokines are the dominant factors guiding the development of Th1/Th2/Th17 cells. We are investigating the role of intracellular transcription factors (STAT4, T-bet, GATA-3 and ROR gt) which regulate the development of Th1/Th2/Th17 cells. Optimal activation of naïve T cells requires at least two signals. Signal one is delivered by engagement of T cell receptor on T cells and peptide-MHC complex on antigen presenting cells (APC).
Signal two is provided by costimulatory molecules on APC binding to their receptors/ligands on T cells. We are exploring the role of different costimulatory molecules during the development of GD. With the availability of a mouse model for GD, we utilize knockout mice, recombinant proteins, monoclonal antibodies and synthetic peptides in our studies. We employ molecular biological, biochemical and immunological approaches to study the structure-function relationship of TSHR and to map functional epitopes.
Together, our studies are expected to lead to the identification of specific intracellular signaling molecules, costimulatory molecules and cytokine targets that may be significant for therapeutic intervention of GD.
Dr. Seetharam’s research interest is to investigate the molecular mechanisms autoimmune Graves’ disease (GD). His research have focused on the identification of specific intracellular signaling molecules, costimulatory molecules and cytokine targets that may be significant for therapeutic intervention of GD.