Soumitra Ghosh, MD, PhD Associate Professor, Pediatrics Specializatioin: Genetic of Juvenile Diabetes Phone: 414-456-4901 Dr. Ghosh's CV Email Dr. Ghosh
My research focuses on two main areas: functional genomics and genetic mapping of Type 1 diabetes (T1D). In this disease, effector T cells kill the insulin-producing beta cells of the pancreas. Through gene expression and pathways analyses (functional genomics), we have found that apoptosis (programmed cell death) of protective, regulatory T cells possibly leads to human T1D, since effector T cells are free to destroy beta cells. Recently, we have found that regulatory T cells undergo a similar apoptosis under IL-2 deprivation and have been able to both reverse apoptosis and delay onset of disease by IL-2 therapy in a mouse model for T1D. In addition, we are investigating the use of apoptosis of regulatory T cells as a biomarker for future disease. Finally, in an attempt to circumvent the early death of regulatory T cells we are optimizing pathways for generating more potent, induced regulatory T cells (made from effector T cells) to abrogate disease.
Our second main area of interest involves both candidate gene analysis and genome-wide association of T1D (GWA). Over the years, we have collected DNA from more than 400 families with T1D (age of onset <17 years) living in Wisconsin and 800 families from Finland (age of onset 15- 39 years). Finland has the highest incidence of disease in the world and no-one has investigated the genetics of older-onset T1D. We have shown that the IL-2 receptor (IL-2Ra) gene accelerates disease onset without being associated with T1D in the older-onset Finnish sample. This, together with our findings of the IL-2 pathway being important in apoptosis of human regulatory T cells, opens up a new avenue for preventative therapy based on solid genetics grounding. We are now investigating the role of Type 2 diabetes genes in the later-onset sample.
Our main work in the future will be to finish the GWA on the Finnish sample and initiate work on the epigenetics of low IL-2 production and reduction of HLA gene expression in human T1D. HLA genes have the strongest effect in T1D. We have also initiated a project to fine map across the HLA region, which will also include high-throughput sequencing. Finally, we have just initiated a small project to study the proteomic profiles of membrane proteins in regulatory T cells.