Publications by authors named "C E Whitworth"
Purpose: P300 is a lysine acetyltransferase that plays a significant role in regulating transcription and the nuclear acetylome. While P300 has been shown to be required for the transcription of certain early flow responsive genes, relatively little is known about its role in the endothelial response to hemodynamic fluid stress. Here we sought to define the role of P300 in mechanotransduction of fluid shear stress in the vascular endothelium.
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- Mutations in the KRAS protein are common in cancer, with a notable example being the G12C mutation, which has targeted treatments.
- Researchers developed a novel small molecule that can degrade many KRAS mutations, demonstrating more effective and lasting effects compared to traditional inhibition.
- Their findings showed that this approach not only effectively kills cancer cells with KRAS mutations but also spares normal cells, leading to reduction in tumors in animal models.
Somatic activating mutations in are common drivers of vascular and lymphatic malformations. Despite common biophysical signatures of tissues susceptible to lesion formation, including compliant extracellular matrix and low rates of perfusion, lesions vary in clinical presentation from localized cystic dilatation to diffuse and infiltrative vascular dysplasia. The mechanisms driving the differences in disease severity and variability in clinical presentation and the role of the biophysical microenvironment in potentiating progression are poorly understood.
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- Targeted protein degradation is a new approach in drug discovery, but the natural half-life of proteins greatly influences how effective these degraders are, and this relationship hasn’t been thoroughly studied.
- Research shows that short-lived proteins can misleadingly appear to be degraded by agents that actually halt protein synthesis, like GSPT1 degraders and cytotoxic drugs.
- The findings indicate that understanding a target protein's half-life is crucial for selecting targets and designing control experiments to validate the effectiveness of new protein degrading agents.
Article Synopsis
- Microphysiological and organ-on-chip platforms aim to improve human disease models and drug development due to low success rates in clinical interventions.
- Current platforms often depend on animal or synthetic materials that fail to accurately replicate human physiology, especially in diseases influenced by the extracellular matrix.
- The study introduces human cell-derived matrix (hCDM) hydrogels, which enhance the modeling of blood vessels by using components from human fibroblasts, promoting better vascularization and more effective disease modeling.