Publications by authors named "Jenni K Durieux"
Article Synopsis
- NAD is essential for many cellular processes, and GNE-618 is an NAMPT inhibitor that decreases NAD levels, leading to cell death in lab models.
- Cells with NAPRT1 can survive NAMPT inhibition by converting nicotinic acid to NAD, but this protection is only effective if the nicotinic acid is present before NAD is depleted.
- Tumor cells are particularly vulnerable to GNE-618 because they cannot produce NAD through de novo synthesis, and higher NAMPT levels correlate with greater sensitivity to the inhibitor, suggesting a potential method for identifying effective treatments.
Oncogenic mutations in the mitogen activated protein kinase (MAPK) pathway are prevalent in human tumors, making this pathway a target of drug development efforts. Recently, ATP-competitive Raf inhibitors were shown to cause MAPK pathway activation via Raf kinase priming in wild-type BRaf cells and tumors, highlighting the need for a thorough understanding of signaling in the context of small molecule kinase inhibitors. Here, we present critical improvements in cell-line engineering and image analysis coupled with automated image acquisition that allow for the simultaneous identification of cellular localization of multiple MAPK pathway components (KRas, CRaf, Mek1 and Erk2).
View Article and Find Full Text PDF