There are three major ongoing projects in our laboratory: 1. Transcription factors that establish and maintain T-cell specific gene expression. TCF-1 imposes T cell identity early in T cell development, but the mechanisms employed are uncertain, and are the focus of intense investigation in our laboratory. We're using conditional alleles of TCF-1 to determine whether TCF-1 controls expression of a common set of T cell genes throughout development, or if TCF-1 instead plays different roles in mature T cells. 2. The development and function of innate lymphoid cells. Innate lymphoid cells have transcriptional programs that appear to mirror those of T cells. The comparison of innate lymphocyte cell development with T cell development provides an opportunity to understand the factors that underlie the shared as well as the unique features and functions of these apparently closely related cell lineages. We have identified the earliest known precursors committed to innate cell lineages, and are characterizing the functions of transcription factors expressed in these early innate lymphocyte precursors. 3. Transcription factors in thymic epithelial cells. Distinct transcription factors are expressed in fetal thymic epithelial cells, and in different subtypes of thymic epithelial cells. We are using knockout mice to determine the functions of these factors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011633-05
Application #
10014741
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Johnson, John L; Georgakilas, Georgios; Petrovic, Jelena et al. (2018) Lineage-Determining Transcription Factor TCF-1 Initiates the Epigenetic Identity of T Cells. Immunity 48:243-257.e10
Das, Arundhoti; Harly, Christelle; Yang, Qi et al. (2018) Lineage specification in innate lymphocytes. Cytokine Growth Factor Rev 42:20-26
Smith, Michelle J; Reichenbach, Dawn K; Parker, Sarah L et al. (2017) T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and continued thymic microenvironment interaction. JCI Insight 2:
Zhang, Kangning; Xu, Xingyuan; Pasha, Muhammad Asghar et al. (2017) Cutting Edge: Notch Signaling Promotes the Plasticity of Group-2 Innate Lymphoid Cells. J Immunol 198:1798-1803
Larsen, Brian M; Bhandoola, Avinash (2017) A novel role for p53 in self-tolerance. Blood 130:388-389
Nish, Simone A; Zens, Kyra D; Kratchmarov, Radomir et al. (2017) CD4+ T cell effector commitment coupled to self-renewal by asymmetric cell divisions. J Exp Med 214:39-47
Morgado-Palacin, Isabel; Day, Amanda; Murga, Matilde et al. (2016) Targeting the kinase activities of ATR and ATM exhibits antitumoral activity in mouse models of MLL-rearranged AML. Sci Signal 9:ra91
Harly, Christelle; Bhandoola, Avinash (2016) A doppelgänger of T cell development. Cell Cycle 15:479-80
Manna, Sugata; Bhandoola, Avinash (2016) Intrathymic Injection. Methods Mol Biol 1323:203-9
Yang, Qi; Ge, Moyar Q; Kokalari, Blerina et al. (2016) Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice. J Allergy Clin Immunol 137:571-8

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