Biology subjects

Chen, J. W.

Publications and source records attributed to Chen, J. W..

2 recordsLinked to original sources

bioRxiv2020

STAMPede: A Precision Oncology Catalogue of Solid Tumors

Molecular profiling of tumor specimens is a key contributor in the application of precision medicine toward patient care in oncology. The presence of genetic mutational data may provide insight into the etiology of the cancer and inform about the available therapeutic options for patients diagnosed with various cancer types. However, the ability to centrally organize, structure, and visualize this genetic data can be hindered by the lack of necessary computational infrastructure. Here we present a somatic tumor data visualization portal titled STAMPede that utilizes tumor sequencing data from an in-house solid tumor oncology sequencing panel at Stanford Health Care. STAMPede is intended to provide Stanford healthcare providers and clinical researchers an easy to navigate web-based portal to query and display gene-, variant-, and cancer-level summary statistics.

genomics↗

bioRxiv2020

Obtusaquinone is a cysteine modifying compound that targets Keap1 for degradation

We have previously identified the natural product Obtusaquinone (OBT) as a potent antineoplastic agent with promising in vivo activity in glioblastoma and breast cancer through the activation of oxidative stress; however, the molecular properties of this compound remained elusive. We used a multidisciplinary approach comprising medicinal chemistry, quantitative mass spectrometry-based proteomics, functional studies in cancer cells, pharmacokinetic analysis, as well as mouse xenograft models to develop and validate novel OBT analogs and charaterize the molecular mechanism of action of OBT. We here show that OBT and analogs, which have improved pharmacological properties, bind to cysteine residues with particular affinity to cysteine-rich Keap1, a member of the CUL3 ubiquitin ligase complex. This binding promotes an overall stress response and results in ubiquitination and proteasomal degradation of Keap1 and downstream activation of the Nrf2 pathway.

cancer biology↗