Aim 1 will 1 examine whether Pax-3 and genes that are regulated by oxidative or hypoxic stress compete for transcription factor binding and transcription regulation.
Aim 2 will examine whether the adapter factor, p300/CBP, which regulates oxidative and hypoxia-responsive genes, participates in the regulation of Pax-3.
Aim 3 will test whether overexpression of factors that regulate both developmental control and stress-responsive genes protects embryos from the altered gene expression, apoptosis, and NTD associated with excess glucose.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK058300-04
Application #
6643452
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Jones, Teresa L Z
Project Start
2000-09-01
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2005-08-31
Support Year
4
Fiscal Year
2003
Total Cost
$249,750
Indirect Cost
Name
Joslin Diabetes Center
Department
Type
DUNS #
071723084
City
Boston
State
MA
Country
United States
Zip Code
02215
Jung, Jin Hyuk; Iwabuchi, Kumiko; Yang, Zhihong et al. (2016) Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine. Sci Rep 6:28452
Sanders, Kaitlyn; Jung, Jin Hyuk; Loeken, Mary R (2014) Use of a murine embryonic stem cell line that is sensitive to high glucose environment to model neural tube development in diabetic pregnancy. Birth Defects Res A Clin Mol Teratol 100:584-91
Loeken, Mary R (2014) Opportunities and challenges for repair of macrovascular disease using circulating blood-derived progenitor cells. Diabetes Metab Res Rev 30:554-5
Wei, Dan; Loeken, Mary R (2014) Increased DNA methyltransferase 3b (Dnmt3b)-mediated CpG island methylation stimulated by oxidative stress inhibits expression of a gene required for neural tube and neural crest development in diabetic pregnancy. Diabetes 63:3512-22
Lee, Hyung-Yul; Wei, Dan; Loeken, Mary R (2014) Lack of metformin effect on mouse embryo AMPK activity: implications for metformin treatment during pregnancy. Diabetes Metab Res Rev 30:23-30
Loeken, Mary R (2014) Intersection of complex genetic traits affecting maternal metabolism, fetal metabolism, and neural tube defect risk: looking for needles in multiple haystacks. Mol Genet Metab 111:415-7
Loeken, Mary R (2012) A new role for pancreatic insulin in the male reproductive axis. Diabetes 61:1667-8
Wu, Y; Viana, M; Thirumangalathu, S et al. (2012) AMP-activated protein kinase mediates effects of oxidative stress on embryo gene expression in a mouse model of diabetic embryopathy. Diabetologia 55:245-54
Zabihi, Sheller; Loeken, Mary R (2010) Understanding diabetic teratogenesis: where are we now and where are we going? Birth Defects Res A Clin Mol Teratol 88:779-90
Chappell Jr, James H; Wang, Xiao Dan; Loeken, Mary R (2009) Diabetes and apoptosis: neural crest cells and neural tube. Apoptosis 14:1472-83

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