Publications by authors named "Alison L Stewart"
Article Synopsis
- Prokaryotic Cas1-Cas2 complexes help bacteria develop immunity against mobile genetic elements (MGEs) by integrating their DNA into CRISPR sites, but the exact process of this adaptation isn't fully understood.
- * In E. coli, the chaperone protein DnaK was found to inhibit the binding and integration of MGE DNA by Cas1-Cas2, thereby preventing unwanted self-targeting during the naive adaptation phase.
- * Deleting DnaK or mutating its binding domain enhances naive adaptation, indicating its role in regulating when Cas1-Cas2 can target MGE DNA and avoiding potential harm from the bacteria's own DNA.*
Novel therapeutic approaches are urgently required for multiple myeloma (MM). We used a phenotypic screening approach using co-cultures of MM cells with bone marrow stromal cells to identify compounds that overcome stromal resistance. One such compound, BRD9876, displayed selectivity over normal hematopoietic progenitors and was discovered to be an unusual ATP non-competitive kinesin-5 (Eg5) inhibitor.
View Article and Find Full Text PDFEfforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function.
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