A5090099805- RNA Interference and Gene Delivery
- Synthesis and bioactivity of alkaloids
- Synthesis and Biological Evaluation
- Hippo pathway signaling and YAP/TAZ
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Prostate Cancer Treatment and Research
- Cancer therapeutics and mechanisms
- Lipid Membrane Structure and Behavior
- FOXO transcription factor regulation
- Protein Degradation and Inhibitors
Canada's Michael Smith Genome Sciences Centre
2024
University of British Columbia
2020-2024
Therapy-induced neuroendocrine prostate cancer (t-NEPC) is a highly aggressive subtype of with poor patient survival. Emerging evidence indicates that t-NEPC can develop when adenocarcinoma cells acquire stem-like cell signaling in the presence androgen receptor inhibition, followed by redifferentiation toward lineage and subsequent progression. Whether controlled core pluripotency stem genes (e.g., LIN28 SOX2) remains unknown. Here, we report transcription LIN28B isoform SOX2 were...
Lin28 is a pluripotency factor that regulates cancer cell stem-like phenotypes to promote development and therapy-resistant tumor progression. It acts through its cold shock domain zinc knuckle (ZKD) interact with the Let-7 pre-microRNA block biosynthesis. Chemical inhibition of from interacting presents therapeutic strategy for therapy. Herein, we present computer-aided small molecules by in silico screening 18 million compounds ZINC20 library, followed biological validation 163 predicted...
Clinically used topoisomerase II (TOP2) inhibitors are poison that induce DNA damage to cause cancer cell death. However, they can also destroy benign cells and thereby show serious side effects, including cardiotoxicity drug-induced secondary malignancy. New TOP2 with a different mechanism of action (MOA), such as catalytic inhibitors, needed more effectively control tumor growth. We have applied computer-aided drug design develop new group small molecule derivatives our previously...
When formulating mRNA into lipid nanoparticles (LNP), various copy numbers of are encapsulated, leading to a distribution loading levels within the LNPs. It is unclear whether level affects functional delivery message. Here we show that depending on level, LNPs exhibit distinct mass densities and can be fractionated via ultracentrifugation. Upon fractionation, investigated if influence LNP sizing, composition, morphology. We further conducted