Takeshi Egawa, M.D., Ph.D.

Associate Professor
Pathology and Immunology
Immunobiology

Immunology Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-747-2516

  • 314-362-8776

  • 314-362-8740

  • 314-362-8888

  • 8118

  • CSRB 7719

  • tegawa@WUSTL.EDU

  • lymphocyte development, adaptive immunity, transcription factors, cytokines, oncogenesis

  • Gene regulation for lymphocyte development and adaptive immune responses

Research Abstract:

My laboratory’s main interest is understanding molecular mechanisms by which the development of lymphocytes, their clonal expansion and effector functions are regulated. We approach these questions by using mouse genetics, pathogen infection models, tumor transplantation combined with checkpoint blockade.

1) Cell fate choices, lineage commitment and maintenance of lymphocytes.
Developing cells differentiating to a specific lineage acquire gene expression profiles linked to their professional functions as they lose developmental plasticity. These changes in gene expression take place at developmental checkpoints at which developing precursor cells choose one fate over the other. These include bifurcations between myeloid and lymphoid, B and T, Th1 and Th2 lineages, CD8 effector and memory cells etc. Currently, our research focuses on T cell differentiation during chronic viral infection or in the tumor microenvironment and defines the molecular mechanisms that induces so-called "T cell exhaustion" and restore functions of "exhausted" T cells.

2) Elucidation of gene regulatory pathways for durable clonal expansion of lymphocytes.
Clonal expansion is a hallmark feature of adaptive immunity. Lymphocyte precursors and activated lymphocytes robustly proliferate during the development or an immune response to establish diverse repertoire and also to amplify the magnitude of immune responses. While such rapid cell proliferation is required for host protection against infection or cancers, it is a metabolically demanding process and concurrently harbors the risk of oncogenesis due to replication stress. In particular, developing lymphocytes and germinal center B cells elevate endogenous DNA damage due to rearrangement of antigen receptors and somatic hypermutation of immunoglobulin, respectively. Our goal is to elucidate gene regulatory mechanisms that allow lymphocytes to achieve requisite clonal expansion and simultaneously protect them from oncogenic transformation.

Selected Publications:

Etzensperger R, Kadakia T, Tai X, Alag A, Guinter TI, Egawa T, Erman B, Singer A. (2017). Identification of lineage-specifying cytokines that signal all CD8+-cytotoxic-lineage-fate `decisions` in the thymus. Nat. Immunol. 18:1218-1227. PMID: 28945245.

Iwata A, Durai V, Tussiwand R, Briseño CG, Wu X, Grajales-Reyes GE, Egawa T, Murphy TL, Murphy KM. (2017). Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF-IRF4 transcription factor complex. Nat Immunol. 18:563-572. PMID: 28346410.

Inoue T, Shinnakasu R, Ise W, Kawai C, Egawa T, Kurosaki T. (2017). The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help. J. Exp. Med. 214:1181-1198. PMID: 28351982.

Chou C, Verbaro DJ, Tonc E, Holmgren M, Cella M, Colonna M, Bhattacharya D, Egawa T. (2016). The Transcription Factor AP4 Mediates Resolution of Chronic Viral Infection through Amplification of Germinal Center B Cell Responses. Immunity. 45:570-582. PMID: 27566940.

Ebihara T, Song C, Ryu SH, Plougastel-Douglas B, Yang L, Levanon D, Groner Y, Bern MD, Stappenbeck TS, Colonna M, Egawa T, Yokoyama WM. (2015). Runx3 specifies lineage commitment of innate lymphoid cells. Nat Immunol. 16:1124-33. PMID: 26414766.

Kim B, Sasaki Y, & Egawa T. (2015). Restriction of Nonpermissive RUNX3 Protein Expression in T Lymphocytes by the Kozak Sequence. J. Immunol. 195:1517-23. PMID: 26170388.

Chou C., Pinto A.K., Curtis J.D., Persaud S.P., Cella M., Lin C.C., Edelson B.T., Allen P.M., Colonna M., Pearce E.L., Diamond M.S., & Egawa T. (2014). cMyc-induced expression of the transcription factor AP4 sustains CD8+ T cell activation to protect against microbial infection. Nat Immunol. 2014; 15:884-93. PMID: 25029552.

Henson, D.M., Chou, C, Sakurai, N. & Egawa, T. (2014). A Silencer-Proximal Intronic Region Is Required for Sustained CD4 Expression in Postselection Thymocytes. J. Immunol. 192:4620-4627. PMID: 24729613.

Satpathy, A.T., Briseo, C.G., Cai, X., Michael, D.G., Chou, C., Hsiung, S., Bhattacharya, D., Speck, N.A., Egawa, T. (2014). Runx1 and Cbfβ regulate the development of Flt3+ dendritic cell progenitors and restrict myeloproliferative disorder. Blood. 123:2968-2977. PMID: 24677539.

Egawa T* and Littman DR*. Transcription factor AP4 modulates reversible and epigenetic silencing of the Cd4 gene. (2011). Proc Natl Acad Sci U S A. Sep 6;108:14873-8. PMID: 21873191. (* co-corresponding authors)

Last Updated: 10/31/2017 7:37:33 PM

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