Srikanta Jana, PhD
Type 1 Diabetes is an autoimmune disorder in which T cells destroy insulin-producing beta cells within the islets resulting in lifelong dependency on exogenous insulin. It is a multi-factorial disease. Influencing factors could vary from genetics, epigenetics to environment. To imagine a day when T1D simply never occurs research should be aimed at prevention along with a cure. Besides identifying genes that predispose individuals to the disease we need to develop a deeper understanding of how these gene products, namely proteins, communicate with each other to result in an aggressive autoimmune reaction at the cellular level. Study at this level will help to develop micro-molecule/s which could be used for prevention/therapy at an early stage of the disease. There are several mechanisms to control autoreactive T cells at the cellular level, and one of those is direct suppression of the autoreactive T cells by Regulatory-T cells (Treg). Foxp3 is a master regulator for Treg function and development. Although these Tregs mainly originate from the thymus, they are generated in the periphery too. In vitro CD4+CD25- T cells can be differentiated to Treg cells raising the hope for a potential Treg source for prevention/ therapy. The generation of peripheral adaptive Tregs is going to have a pressing need given that we have already established early death of natural Tregs in human T1D (PLoS ONE. 2:e146,2007).
Some of my key research programs that under investigation:
- Study the homeostasis of Treg in T1D animal model (NOD mice) and the quality of Treg.
- Unraveling the molecular mechanisms underlying TGF-b induced Foxp3 expression, to optimize generation of adaptive, autologous Tregs for T1D prevention in animals, and eventually in humans.
Publications:
1. Ghosh, A. K.; Jana, S.; Das, T.; Sa, G.; Mandal, N. and Ray, P. K. Protection by Protein A of apoptotic cell death caused by anti-AIDS drug Zidovudine. Biochem. Biophys. Res. Commun. 1999: 264: 601-604.
2. Glisic-Milosavljevic S, Waukau J, Jana S, Jailwala P, Rovensky J, Ghosh S. Comparison of apoptosis and mortality measurements in peripheral blood mononuclear cells (PBMCs) using multiple methods. Cell Prolif. 2005 Oct;38(5):301-11.
3. Glisic-Milosavljevic S, Waukau J, Jailwala P, Jana S, Khoo HJ, Albertz H, Woodliff J, Koppen M, Alemzadeh R, Hagopian W, Ghosh S. At-Risk and Recent- Onset Type 1 Diabetic Subjects Have Increased Apoptosis in the CD4+CD25+ T-Cell Fraction. PLoS ONE. 2007 Jan 3;2:e146.
Abstracts
1 Pati,N.; Waukau, J.; Jana, S., Schowinsky, V.; Koppen, M.; Vaughan, K.; Meyer, L.; Hessner, M.; Wang, X.; Woodliff, J.; Johnson B. and Ghosh, S. In vitro role of Suppressor cells and analysis of gene expression in TIDM. 6th international Congress of the Immunology of Diabetes Association, 2002.
2 Pati,N.; Jana, S.; Waukau, J.; Schroeder, K.; Woodliff, J.; Johnson B. and Ghosh, S. Behaviour of Suppressor CD4+CD25+ anergic cells in response to TCR stimulation and co-stimulation. 63rd Scientific Session by ADA, 2003, USA.
4. Jana, S.; Waukau, J.; Milosavljevic S.; and Ghosh, S. An in vitro suppression study with CD25+low and CD25- as responder T cells. Keystone Symposia – regulatory/Suppressor T cells, 2004.