We are studying the molecular mechanisms involved in age-dependent thymic involution and T-cell aging. We have demonstrated that expression of beta-catenin in thymocytes in CAT-Tg mice results in accelerated age-dependent thymic involution and aging. Recent analysis demonstrated that expression of beta-catenin inhibits proliferation of developing thymocytes, causes DNA damage,induces oncogene-induced-senescence (OIS) and p53-dependent apoptosis. We believe that this may be a reason why the expression of the powerful oncogene, beta-catenin, does not result in thymic tumors but causes thymic involution. With regard to the observation that expression of beta catenin accelerated thymic involution, we plan to examine if DNA damage, namely OIS and p53-dependent apoptosis, are features of normal aging in wild type mice.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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National Institute on Aging
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Sharma, Archna; Berga-Bolanos, Rosa; Sultana, Dil Afroz et al. (2013) IL-4 and IL-4 receptor expression is dispensable for the development and function of natural killer T cells. PLoS One 8:e71872
Sharma, A; Sen, J M (2013) Molecular basis for the tissue specificity of ?-catenin oncogenesis. Oncogene 32:1901-9
Yu, Qing; Sharma, Archna; Ghosh, Amalendu et al. (2011) T cell factor-1 negatively regulates expression of IL-17 family of cytokines and protects mice from experimental autoimmune encephalomyelitis. J Immunol 186:3946-52
Yu, Qing; Sharma, Archna; Sen, Jyoti Misra (2010) TCF1 and beta-catenin regulate T cell development and function. Immunol Res 47:45-55
Staal, Frank J T; Sen, Jyoti M (2008) The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis. Eur J Immunol 38:1788-94
Xu, Mai; Yu, Qing; Subrahmanyam, Ramesh et al. (2008) Beta-catenin expression results in p53-independent DNA damage and oncogene-induced senescence in prelymphomagenic thymocytes in vivo. Mol Cell Biol 28:1713-23