Immune Cells and Inflammation Section
Description of Research Program
Research in our laboratory focuses on the study of immunity, autoimmunity and inflammation. In particular, we are interested in understanding the role of peripheral, brain associated and gut-associated immune cells, as well as the gut-microbiota in the development of age-related chronic systemic inflammation and age-related neurological ailments including EAE, Parkinson’s and Alzheimer’s disease.
Ongoing projects include:
Study of transcription factors that regulate the development, maintenance and aging of conventional and innate immune cells.
Study of innate and adaptive immune cells in chronic neurological diseases, including EAE, Parkinson’s and Alzheimer’s disease.
Age-associated systemic inflammation and its role in chronic neurological diseases.
• Molecular Biology
Findings and Selected Publications:
Yu, Q., Sharma, A., Oh, S. Y., Moon, H. G., Hossain, M. Z., Salay, T. M., Leeds, K. E., Du, H., Wu, B., Waterman, M. L., Zhu, Z., Sen. J. M. T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-gamma. Nature Immunology. 9:992-9, 2009.
Sharma, A., Chen, Q., Nguyen, T., Yu, Q. and Sen, J. M. T cell factor-1 and β-catenin control the development of memory-like CD8 thymocytes. Journal of Immunology. 188:3859-68, 2012. **Published with a comment, which accompanies the top 10% papers.
Sharma, A., Berga-Bolanos, R. and Sen, J. M. T cell factor-1 controls the lifetime of CD4+ CD8+ thymocytes in vivo and distal T cell receptor alpha-chain rearrangement required for NKT cell development. PLoS ONE, 9 (12), e0115803. Doi:10.1371/journal.pone.0115803, 2014.
Berga-Bolanos, R., Sharma, A., Steinke, F. C., Pyaram, K., Kim, Y-H., Sultana, A. F., Fang, J. X., Chang, C-H., Xue, H-H., Heller, N. M. and Sen, J. M. Beta-Catenin is required for the differentiation of iNKT2 and iNKT17 cells that augment IL-25-dependent lung inflammation. BMC Immunology. 16:62-72, 2015.
Wu, T., Shin, H. M., Moseman, E. A., Ji, Y., Huang, B., Harly, C., Sen, J. M., Berg, L. J., Gattinoni, L., McGavern, D. B. and Schwartzberg, P. L. TCF1 is required for the T follicular helper cell response to viral infection. Cell Reports 12:2099-110, 2015.
Gottimukkala, K., Jangid, R., Patta, I., Sultana. D. A., Sharma, A., Sen, J. M., Galande, S. Regulation of SATB1 during thymocyte development by TCR signaling. Molecular Immunology. 77:34, 2016.
Pyaram, K., Sen, J. M., Chang, G. H. Temporal regulation of Wnt/b-catenin signaling is important for invariant NKT cell development and terminal differentiation. Molecular Immunology. 85:47, 2017.
Zhang, P., Kishimoto, Y., Grammatikakis, I., Gottimukkala, K., Cutler, R. G., Zhang, S., Abdelmohsen, K., Bohr, V. A., Sen, J. M., Myriam Gorospe and Mark P. Mattson. Senolytic therapy ameliorates Ab-associated cellular senescence, inflammation and cognitive decline in Alzheimer’s disease model. Nature Neuroscience. In press. 2019.