This grant over the past 24 years has supported a wide range of studies focused broadly on immunoglobulin gene expression. This renewal concentrates on the forkhead transcription factor, Foxp1. Conventional Foxp1 knockout (KO) leads to mid-gestation cardiovascular dysfunction and lethality. RAG2-/- reconstitution studies demonstrated an intrinsic block of B cell development at the pro-B stage. Thymic development in Foxp1-/--reconstituted RAG-/- mice is normal, but peripheral CD4 T cell subsets and functions are deregulated. We propose to generation conditional Foxp1 knockout mice to study the effects of intrinsic Foxp1 deficiency on B cell and T cell development. We propose to identify Foxp1 target genes to define pathways and mechanisms by which Foxp1 contributes to normal and malignant B cell development. These studies hold clinical relevance in that Foxp1 over- expression is a hallmark of the most aggressive and worst prognostic subset of diffuse large B cell lymphoma. Philip W. Cancer is often caused by abnormal expression of transcription factors, which regulate the expression of many additional genes. Diffuse large B cell lymphoma (DLBCL) accounts for ~40% of cancers of white blood cells. The transcription factor, Foxp1, is abnormally high in the most aggressive form of DLBCL and has been termed a """"""""signature gene"""""""" of this malignancy. By understanding more about Foxp1 and the genes deregulated by its over-expression, we can better understand basic mechanisms underlying DLBCL. PHS 398/2590

Public Health Relevance

Cancer is often caused by abnormal expression of transcription factors, which regulate the expression of many additional genes. Diffuse large B cell lymphoma (DLBCL) accounts for ~40% of cancers of white blood cells. The transcription factor, Foxp1, is abnormally high in the most aggressive form of DLBCL and has been termed a signature gene of this malignancy. By understanding more about Foxp1 and the genes deregulated by its over-expression, we can better understand basic mechanisms underlying DLBCL.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031534-28
Application #
8204575
Study Section
Special Emphasis Panel (ZRG1-IMM-B (02))
Program Officer
Mccarthy, Susan A
Project Start
1982-03-01
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2013-12-31
Support Year
28
Fiscal Year
2012
Total Cost
$249,638
Indirect Cost
$75,977
Name
University of Texas Austin
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Warren, Junco S; Tracy, Christopher M; Miller, Mickey R et al. (2018) Histone methyltransferase Smyd1 regulates mitochondrial energetics in the heart. Proc Natl Acad Sci U S A 115:E7871-E7880
Nie, Hui; Rathbun, Gary; Tucker, Haley (2017) Smyd1C Mediates CD8 T Cell Death via Regulation of Bcl2-Mediated Restriction of outer Mitochondrial Membrane Integrity. J Cell Signal 2:
Rhee, Catherine; Edwards, Melissa; Dang, Christine et al. (2017) ARID3A is required for mammalian placenta development. Dev Biol 422:83-91
Rhee, Catherine; Kim, Jonghwan; Tucker, Haley O (2017) Transcriptional Regulation of the First Cell Fate Decision. J Dev Biol Regen Med 1:
Kim, Dongkyoon; Schmidt, Christian; Brown, Mark A et al. (2017) Competitive Promoter-Associated Matrix Attachment Region Binding of the Arid3a and Cux1 Transcription Factors. Diseases 5:
Li, Hanjun; Liu, Pei; Xu, Shuqin et al. (2017) FOXP1 controls mesenchymal stem cell commitment and senescence during skeletal aging. J Clin Invest 127:1241-1253
Li, Shanru; Morley, Michael; Lu, MinMin et al. (2016) Foxp transcription factors suppress a non-pulmonary gene expression program to permit proper lung development. Dev Biol 416:338-46
Woodworth, Mollie B; Greig, Luciano C; Liu, Kevin X et al. (2016) Ctip1 Regulates the Balance between Specification of Distinct Projection Neuron Subtypes in Deep Cortical Layers. Cell Rep 15:999-1012
Huang, Ching-Jung; Das, Utsab; Xie, Weijun et al. (2016) Altered stoichiometry and nuclear delocalization of NonO and PSF promote cellular senescence. Aging (Albany NY) 8:3356-3374
Kim, Peter Geon; Canver, Matthew C; Rhee, Catherine et al. (2016) Interferon-? signaling promotes embryonic HSC maturation. Blood 128:204-16

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