Publications by authors named "Tamara Vital"
Article Synopsis
- Ewing sarcoma is a cancer primarily affecting children and young adults, driven by the fusion protein EWSR1::FLI1, which disrupts normal chromatin function and gene regulation.
- Researchers developed a high-throughput screening platform to identify small molecules that can modify chromatin accessibility, leading to the discovery of MS0621, which suppresses the growth of Ewing sarcoma cells through cell cycle arrest.
- MS0621 was found to interact with both RNA splicing and chromatin regulatory proteins in an RNA-independent manner, suggesting it alters chromatin activity and offers a promising target for future treatments based on chromatin dysregulation mechanisms.
Chromosomal translocation results in development of an Ewing sarcoma breakpoint region 1-Friend leukemia integration 1 (EWS-FLI1) fusion oncogene in the majority of Ewing sarcoma. The persistent dependence of the tumor for this oncoprotein points to EWS-FLI1 as an ideal drug target. Although EWS-FLI1 transcriptional targets and binding partners are evaluated, the mechanisms regulating EWS-FLI1 protein stability remain elusive.
View Article and Find Full Text PDFPhenotypic cell-based screening is a powerful approach to small-molecule discovery, but a major challenge of this strategy lies in determining the intracellular target and mechanism of action (MoA) for validated hits. Here, we show that the small-molecule BRD0476, a novel suppressor of pancreatic β-cell apoptosis, inhibits interferon-gamma (IFN-γ)-induced Janus kinase 2 (JAK2) and signal transducer and activation of transcription 1 (STAT1) signaling to promote β-cell survival. However, unlike common JAK-STAT pathway inhibitors, BRD0476 inhibits JAK-STAT signaling without suppressing the kinase activity of any JAK.
View Article and Find Full Text PDF