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One or more keywords matched the following properties of Kee, Barbara Lynne
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overview Transcriptional Control of Innate and Adaptive Lymphoid Development and Transformation The execution of an effective immune response with minimal immune-mediated disease requires appropriate control of the development and function of adaptive and innate components of the immune system. B and T lymphocytes are the cells that mediate adaptive immunity; they are highly antigen specific but require substantial expansion and activation prior to promoting an effective immune response. In contrast, natural killer (NK) cells, innate-like T lymphocytes, and the recently identified innate lymphoid cells (ILCs) are lymphocytes that function in innate immunity; they acquire their effector properties during their development and are poised to rapidly confront invading pathogens. All immune system cells develop from a common hematopoietic stem cell (HSC) whose differentiation pathway is controlled in part by the activation and repression of lineage specific gene programs. Our laboratory is interested in understanding how these transcriptional programs are wired and how alterations in these pathways lead to disease such as autoimmunity, asthma and acute leukemia. The E protein class of basic helix-loop-helix (bHLH) transcription factors and their antagonists, the ID proteins, play fundamental roles in the choice between adaptive and innate lymphoid differentiation and they control the precise effector functions exhibited by these cells. Failure to properly control the activity of these proteins leads to immune deficiencies and cancer. The E protein E2A is required for development of B and T lymphocytes due to direct regulation of critical transcriptional networks that specify these lineages from HSCs and multipotent progenitors. Despite a severe T lymphocyte immune deficiency in E2A-deficient mice, the mice develop a disease similar to T lymphocyte acute lymphoblastic leukemia (T-ALL), and the human disease is characterized by recurrent mutations that affect E protein function. We identified a transcriptional cascade involving the transcription factors Notch1 and LEF1 as being critical for leukemia cell survival and we are working toward an understanding of how these transcription factors contribute to both immune deficiency and leukemogenesis. ID2 and ID3 control the development and effector fate of innate lymphoid cells including NK cells, ILCs and NKT cells. Our laboratory has focused on understanding how ID protein expression is regulated in innate lymphoid cells and how the targets of the E protein transcription factors control adaptive and innate lymphoid cell differentiation. Our recent studies led to the identification of ETS1 as a critical regulator of ID2 that promotes NK cell and ILC differentiation, and we are working toward an understanding of how ETS1 and ID2 cooperate to control NK cell maturation and effector function.
One or more keywords matched the following items that are connected to Kee, Barbara Lynne
Item TypeName
Concept Basic Helix-Loop-Helix Transcription Factors
Academic Article E2A proteins: essential regulators at multiple stages of B-cell development.
Academic Article Id3 inhibits B lymphocyte progenitor growth and survival in response to TGF-beta.
Academic Article Transcription factor regulation of B lineage commitment.
Academic Article Growth factor independent 1B (Gfi1b) is an E2A target gene that modulates Gata3 in T-cell lymphomas.
Academic Article Notch1 promotes survival of E2A-deficient T cell lymphomas through pre-T cell receptor-dependent and -independent mechanisms.
Academic Article Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity.
Academic Article Inhibitor of DNA binding 3 limits development of murine slam-associated adaptor protein-dependent "innate" gammadelta T cells.
Academic Article E proteins and the regulation of early lymphocyte development.
Academic Article differential roles for the E2A activation domains in B lymphocytes and macrophages.
Academic Article Inhibitors of DNA binding proteins restrict T cell potential by repressing Notch1 expression in Flt3-negative common lymphoid progenitors.
Academic Article Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2.
Academic Article E2A proteins promote development of lymphoid-primed multipotent progenitors.
Academic Article E and ID proteins branch out.
Academic Article Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development.
Academic Article E2A transcription factors limit expression of Gata3 to facilitate T lymphocyte lineage commitment.
Academic Article ID'ing innate and innate-like lymphoid cells.
Academic Article Transcription factor ID2 prevents E proteins from enforcing a naïve T lymphocyte gene program during NK cell development.
Academic Article Cutting Edge: Lymphomyeloid-Primed Progenitor Cell Fates Are Controlled by the Transcription Factor Tal1.
Academic Article E Protein Transcription Factors as Suppressors of T Lymphocyte Acute Lymphoblastic Leukemia.
Academic Article Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T-ALL.
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  • Basic Helix Loop Helix Transcription Factors