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1.  Loss of insulin signaling in vascular endothelial cells accelerates atherosclerosis in apolipoprotein E null mice 
Cell metabolism  2010;11(5):379-389.
Summary
To determine whether insulin action on endothelial cells promotes or protects against atherosclerosis, we generated apolipoprotein E null mice in which the insulin receptor gene was intact or conditionally deleted in vascular endothelial cells. Insulin sensitivity, glucose tolerance, plasma lipids, and blood pressure were not different between the two groups, but atherosclerotic lesion size was more than 2-fold higher in mice lacking endothelial insulin signaling. Endothelium-dependent vasodilation was impaired and endothelial cell VCAM-1 expression was increased in these animals. Adhesion of mononuclear cells to endothelium in vivo was increased 4-fold compared with controls, but reduced to below control values by a VCAM-1 blocking antibody. These results provide definitive evidence that loss of insulin signaling in endothelium, in the absence of competing systemic risk factors, accelerates atherosclerosis. Therefore, improving insulin sensitivity in the endothelium of patients with insulin resistance or type 2 diabetes may prevent cardiovascular complications.
doi:10.1016/j.cmet.2010.03.013
PMCID: PMC3020149  PMID: 20444418
2.  MLL-AF9-Induced Leukemogenesis Requires Co-Expression of the Wild Type Mll Allele 
Cancer cell  2010;17(2):148-159.
SUMMARY
Oncogenic fusion proteins are capable of initiating tumorigenesis but the role of their wild-type counterparts in this process is poorly understood. The mixed lineage leukemia (MLL) gene undergoes chromosomal translocations, resulting in the formation of oncogenic MLL fusion proteins (MLL-FPs). Here we show that menin recruits both wild-type (wt) MLL and MLL-AF9 to the loci of Hox genes to activate their transcription. Wild-type MLL not only catalyzes histone methylation at key target genes but also controls distinct MLL-AF9-induced histone methylation. Notably, the wt Mll allele is required for MLL-AF9-induced leukemogenesis and maintenance of MLL-AF9-transformed cells. These findings suggest an essential cooperation between an oncogene and its wild-type counterpart in MLL-AF9-induced leukemogenesis.
doi:10.1016/j.ccr.2009.12.034
PMCID: PMC2830208  PMID: 20159607
MLL; mixed lineage leukemia; MLL fusion protein; MLL-AF9; menin; histone methylation; Leukemia stem cells; epigenetics

Results 1-2 (2)