Littman Laboratory: T Cell Development and Retroviral Pathogenesis

Takeshi Egawa
Special Fellow of the Leukemia & Lymphoma Society
Ph.D. Osaka University Graduate School of Medicine 2002
M.D. Osaka University 1994
Takeshi.Egawa@nyumc.org

I am interested in figuring out gene regulation governing cell fate decisions of blood cells. To attain this goal, I utilize T cell development as a model system and study functions of transcriptional regulators that play important roles in thymocyte differentiation.

During my postdoctoral training in the Littman laboratory, I have focused on functions of the Runx family of transcription factors and a BTB-POZ protein, ThPOK. Runx proteins play an important role in regulation of CD4/CD8 coreceptor expression and, among the three Runx proteins, Runx3 function is critically important for generation of the cytotoxic lineage of T cells, whereas ThPOK is essential for helper T cell development. Through mouse genetics, I have demonstrated that ThPOK functions as a commitment factor for the helper T cell differentiation pathway through inhibition of Runx activity.

During cytotoxic T cell differentiation, Runx proteins, Runx3 in particular, are required for epigenetic silencing of the Cd4 gene. Epigenetic gene silencing is considered to be an important process for gene regulation in cell differentiation and cancerous transformation. Because Runx proteins have also been shown to be important for development of hematopoietic, mesenchymal and neuronal cells and their aberrant functions are linked to cancers, I believe that studies of Runx-mediated gene regulation should contribute to better understanding of gene regulation linked to normal cell differentiation and cancer development. Towards this goal, I am currently developing systems to understand how Runx proteins regulate gene silencing and what other molecules participate in establishment of epigenetic gene regulation, in cooperation with Runx.

Selected Publications

Egawa T, Littman DR. (2008). ThPOK acts late in specification of the helper T cell lineage and suppresses Runx-mediated commitment to the cytotoxic T cell lineage.
Nat. Immunol. 9, 1131-9.

Egawa T, Kreslavsky T, Littman DR, von Boehmer H. (2008). Lineage diversion of T cell receptor transgenic thymocytes revealed by lineage fate mapping.
PLoS ONE. 3, e1512.

Egawa T, Tillman RE, Naoe Y, Taniuchi I, Littman DR. (2007). The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells.
J. Exp. Med. 204, 1945-57.

Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, Levy DE, Leonard WJ, Littman DR. (2007). IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat. Immunol. 8, 967-74.

Grueter B, Petter M, Egawa T, Laule-Kilian K, Aldrian CJ, Wuerch A, Ludwig Y, Fukuyama H, Wardemann H, Waldschuetz R, Möröy T, Taniuchi I, Steimle V, Littman DR, Ehlers M. (2005). Runx3 regulates integrin alpha E/CD103 and CD4 expression during development of CD4-/CD8+ T cells. J. Immunol. 175, 1694-1705.

Egawa, T., Eberl, GE., Taniuchi, I., Benlagha, K., Bendelac, A., Littman, DR. (2005). Genetic Evidence Supporting Selection of the V-alpha14i NKT Cell Lineage from Double Positive Thymocyte Precursors. Immunity 22, 705-16.

Tokoyoda, K., Egawa, T., Sugiyama, T., Choi, B.I., Nagasawa, T. (2004). Cellular Niches Controlling B Lymphocyte Behavior within Bone Marrow during Development. Immunity 20, 707-718.

Ara, T., Tokoyoda, Sugiyama, T., Kawabata, K., Egawa, T., Nagasawa, T. (2003) Long-Term Hematopoietic Stem Cells Require Stromal Cell-Derived Factor-1 for Colonizing Bone Marrow during Ontogeny. Immunity 19, 257-267.

Egawa, T., Albrecht, B., Favier, B., Sunshine, M.J., Mirchandani, K., O'Brien, W., Thome, M., Littman, D.R. (2003). Requirement for CARMA1 in Antigen Receptor-Induced NF-kB Activation and Lymphocyte Proliferation. Curr. Biol. 13, 1252-1258.

Taniuchi, I., Osato, M., Egawa, T., Sunshine, M.J., Bae, S.C., Komori, T., Ito, Y., Littman, D.R. (2002). Differential Requirements for Runx Proteins in CD4 Repression and Epigenetic Silencing during T Lymphocyte Development. Cell 111, 621-633.

Egawa, T., Kawabata, K., Kawamoto, H., Amada, K., Okamoto, R., Fujii, N., Kishimoto, T., Katsura, Y., & Nagasawa, T. (2001). The earliest stages of B cell development require a chemokine stromal cell derived factor 1 / pre-B-cell growth stimulating factor. Immunity 15, 323-334.