Publications by authors named "Josolyn Chan"

Modern mass spectrometers routinely allow deep proteome coverage in a single experiment. These methods are typically operated at nanoflow and microflow regimes, but they often lack throughput and chromatographic robustness, which is critical for large-scale studies. In this context, we have developed, optimized, and benchmarked LC-MS methods combining the robustness and throughput of analytical flow chromatography with the added sensitivity provided by the Zeno trap across a wide range of cynomolgus monkey and human matrices of interest for toxicological studies and clinical biomarker discovery.

View Article and Find Full Text PDF

Remdesivir (GS-5734; VEKLURY) is a single diastereomer monophosphoramidate prodrug of an adenosine analog (GS-441524). Remdesivir is taken up by target cells and metabolized in multiple steps to form the active nucleoside triphosphate (GS-443902), which acts as a potent inhibitor of viral RNA-dependent RNA polymerases. Remdesivir and GS-441524 have antiviral activity against multiple RNA viruses.

View Article and Find Full Text PDF
Article Synopsis
  • Antisense oligonucleotides (ASOs) are rapidly emerging as important drugs, and their effective quantification is essential for drug development.
  • A new branched DNA method was developed to improve the sensitivity of ASO quantification compared to traditional methods like hybridization immunoassays.
  • This new method demonstrated significantly better sensitivity, achieving a lower limit of quantification (LLOQ) of 31.25 pg/ml in plasma, indicating its superiority in precision and accuracy while reducing interference from hemolysis.
View Article and Find Full Text PDF

Ionizing radiation (IR) not only activates DNA damage response (DDR) in irradiated cells but also induces bystander effects (BE) in cells not directly targeted by radiation. How DDR pathways activated in irradiated cells stimulate BE is not well understood. We show here that extracellular vesicles secreted by irradiated cells (EV-IR), but not those from unirradiated controls (EV-C), inhibit colony formation in unirradiated cells by inducing reactive oxygen species (ROS).

View Article and Find Full Text PDF