Abstract

This is a new application from Dr. Leonard Freedman who proposes to investigate the role of vitamin D3 inducible genes in cell differentiation. Specifically, a select set of genes that are under direct transcriptional induction by the vitamin D receptor (VDR) will be characterized for their ability to induce differentiation of the human myeloid leukemic cell U937 to the monocyte/macrophage pathway.
Four specific aims are proposed: 1) identify which of the vitamin D3 inducible genes in U937 cells are direct targets for the VDR and characterize a select set of these genes for their ability to induce U937 differentiation; 2) examine whether the VDR target genes characterized under the first aim cooperate to synergize U937 differentiation in the absence of the hormone, 3) examine the generality of the differentiation inducing effects of the VDR target genes in other myeloid and in nonmyeloid cells, 4) explore the mechanism for the transcriptional activation of the VDR target genes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK052621-04
Application #
6177973
Study Section
Endocrinology Study Section (END)
Program Officer
Margolis, Ronald N
Project Start
1997-05-27
Project End
2001-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
4
Fiscal Year
2000
Total Cost
$227,070
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Liu, Yan; Asai, Takashi; Nimer, Stephen D (2010) Myelodysplasia: battle in the bone marrow. Nat Med 16:30-2
Wang, Lan; Huang, Gang; Zhao, Xinyang et al. (2009) Post-translational modifications of Runx1 regulate its activity in the cell. Blood Cells Mol Dis 43:30-4
Nimer, Stephen D (2008) MDS: a stem cell disorder--but what exactly is wrong with the primitive hematopoietic cells in this disease? Hematology Am Soc Hematol Educ Program :43-51
Nimer, Stephen D (2008) Is it important to decipher the heterogeneity of ""normal karyotype AML""? Best Pract Res Clin Haematol 21:43-52
Morales, Monica; Liu, Yan; Laiakis, Evagelia C et al. (2008) DNA damage signaling in hematopoietic cells: a role for Mre11 complex repair of topoisomerase lesions. Cancer Res 68:2186-93
Jankovic, Vladimir; Ciarrocchi, Alessia; Boccuni, Piernicola et al. (2007) Id1 restrains myeloid commitment, maintaining the self-renewal capacity of hematopoietic stem cells. Proc Natl Acad Sci U S A 104:1260-5
Mulloy, James C; Jankovic, Vladimir; Wunderlich, Mark et al. (2005) AML1-ETO fusion protein up-regulates TRKA mRNA expression in human CD34+ cells, allowing nerve growth factor-induced expansion. Proc Natl Acad Sci U S A 102:4016-21
Scandura, Joseph M; Boccuni, Piernicola; Massague, Joan et al. (2004) Transforming growth factor beta-induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation. Proc Natl Acad Sci U S A 101:15231-6
Ward, J O; McConnell, M J; Carlile, G W et al. (2001) The acute promyelocytic leukemia-associated protein, promyelocytic leukemia zinc finger, regulates 1,25-dihydroxyvitamin D(3)-induced monocytic differentiation of U937 cells through a physical interaction with vitamin D(3) receptor. Blood 98:3290-300
Yang, W; Rachez, C; Freedman, L P (2000) Discrete roles for peroxisome proliferator-activated receptor gamma and retinoid X receptor in recruiting nuclear receptor coactivators. Mol Cell Biol 20:8008-17

Showing the most recent 10 out of 13 publications