The Regulatory Roles of Wnt Signaling in Thymocyte Development

The Wnt signaling pathway has versatile roles in development, differentiation and oncogenesis. My research focuses on the role of Wnt signaling and the pathway’s effector transcription factors, TCF-1 (T cell factor-1) and LEF-1 (lymphoid enhancer-binding factor 1), in T cell development. TCF-1 and LEF-1 deficiency in thymocytes blocks their development to mature T cells, leading to decreased thymic cellularity. Using gene targeting, gene complementation and in vitro approaches, I am investigating the influence of Wnt signaling on CD4 vs CD8 lineage choice and defining a possible synergistic activity between the Wnt and T cell receptor signaling pathways during thymocyte selection.

Berga-Bolaños R, Zhu WS, Steinke FC, Xue HH, Sen JM. Cell-autonomous requirement for TCF1 and LEF1 in the development of Natural Killer T cells. Mol Immunol. 2015 Dec;68(2 Pt B):484-9. doi: 10.1016/j.molimm.2015.09.017. PubMed PMID: 26490636; PubMed Central PMCID: PMC4636915.

Berga-Bolaños R, Sharma A, Steinke FC, Pyaram K, Kim YH, Sultana DA, Fang JX, Chang CH, Xue HH, Heller NM, Sen JM. β-Catenin is required for the differentiation of iNKT2 and iNKT17 cells that augment IL-25-dependent lung inflammation. BMC Immunol. 2015 Oct 19;16:62. doi: 10.1186/s12865-015-0121-0. PubMed PMID: 26482437; PubMed Central PMCID: PMC4615569.

Steinke FC, Xue HH. From inception to output, Tcf1 and Lef1 safeguard development of T cells and innate immune cells. Immunol Res. 2014 Aug;59(1-3):45-55. doi: 10.1007/s12026-014-8545-9. Review. PubMed PMID: 24847765.

Steinke FC, Yu S, Zhou X, He B, Yang W, Zhou B, Kawamoto H, Zhu J, Tan K, Xue HH. TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4(+) T cell fate and interact with Runx3 to silence Cd4 in CD8(+) T cells. Nat Immunol. 2014 Jul;15(7):646-56. doi: 10.1038/ni.2897. Epub 2014 May 18. PubMed PMID: 24836425; PubMed Central PMCID: PMC4064003.

Yu S, Zhou X, Steinke FC, Liu C, Chen SC, Zagorodna O, Jing X, Yokota Y, Meyerholz DK, Mullighan CG, Knudson CM, Zhao DM, Xue HH. The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy. Immunity. 2012 Nov 16;37(5):813-26. doi:10.1016/j.immuni.2012.08.009. Epub 2012 Oct 25. Erratum in: Immunity. 2014 Jan 16;40(1):166. PubMed PMID: 23103132; PubMed Central PMCID: PMC3501598.