Brigham and Women's Hospital
Smith Building, Room 524
One Jimmy Fund Way
Boston, MA 2115
T lymphocytes (T cells) not only play a central role in adaptive immunity but also are pathogenic in many autoimmune diseases. Better understanding of how the differentiation and activation of T cells is regulated can lead to novel treatments for infectious and autoimmune diseases.
Two lines of research are being conducted in my laboratory.
We have previously identified several transcription factors that are critical for the differentiation and function of T cells. These transcription factors include GATA-3, Ets-1, and c-maf. The focus of this line of research is to understand the mechanism of action of these proteins and to identify their downstream target genes.
Recent genome-wide association studies have shown that a non-synonymous single nucleotide polymorphism (SNP) in the ptpn22 gene is strongly associated with an increased risk of several autoimmune diseases, including SLE, rheumatoid arthritis, and autoimmune diabetes. The ptpn22 encodes a hematopietic non-receptor protein tyrosine phosphatase, namely PTPN22, and the non-synonymous SNP leads to a gain of function variant of PTPN22. We are investigating the physiological function of PTPN22 and the pathogenic mechanism of the non-synonymous SNP in the context of SLE and rheumatoid arthritis.
Zamisch, M., L. Tian, R. Grenningloh, Y. Xiong, K. F. Wildt, M. Ehlers, I. C. Ho, and R. Bosselut. 2009. The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus. J Exp Med 206:2685.
Ho, I. C., T. S. Tai, and S. Y. Pai. 2009. GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation. Nat Rev Immunol 9:125.
Strempel, J. M., R. Grenningloh, I. C. Ho, and D. Vercelli. 2010. Phylogenetic and functional analysis identifies Ets-1 as a novel regulator of the Th2 cytokine gene locus. J Immunol 184:1309.
Lin, B. S., P. Y. Tsai, W. Y. Hsieh, H. W. Tsao, M. W. Liu, R. Grenningloh, L. F. Wang, I. C. Ho, and S. C. Miaw. 2010. SUMOylation attenuates c-Maf-dependent IL-4 expression. Eur J Immunol 40:1174.
Grenningloh, R., T. S. Tai, N. Frahm, T. C. Hongo, A. T. Chicoine, C. Brander, D. E. Kaufmann, and I. C. Ho. 2011. Ets-1 maintains IL-7 receptor expression in periphaerl T cells. J Immunol 186:969.
Last Update: 1/6/2014