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In the breast, cancer stem cells and normal stem cells can arise from different cell types and tap into distinct yet related stem cell programs, according to Whitehead Institute researchers. The differences between these stem cell programs may be significant enough to be exploited by future therapeutics.

Upsetting the balance between protein synthesis, misfolding, and degradation drives cancer and neurodegeneration. Recent cancer treatments take advantage of this knowledge with a class of drugs that block protein degradation, known as proteasome inhibitors. Widespread resistance to these drugs limits their success, but Whitehead researchers have discovered a potential Achilles heel in resistance. With such understandings researchers may be able to target malignancy broadly, and more effectively.

According to Whitehead Institute researchers, cells with malfunctioning mitochondria are unable to proliferate due to a shortage of the amino acid aspartate, not because of an energy crisis, as was once thought. Mitochondrial dysfunction plays a role in a host of relatively rare disorders as well as neurodegenerative disorders, including Parkinson’s disease.

Leveraging a novel system designed to examine the double-strand DNA breaks that occur as a consequence of gene amplification during DNA replication, Whitehead Institute scientists are bringing new clarity to the causes of such genomic damage. Moreover, because errors arising during DNA replication and gene amplification result in chromosomal abnormalities often found in malignant cells, these new findings may bolster our understandings of certain drivers of cancer progression.

Scientists have applied a new method of analyzing cell states to identify a gene required for breast stem cells to differentiate. This gene, RUNX1, is deregulated or mutated in some leukemias and breast cancers. The novel approach, known as PEACS, could also be used to screen for drugs that activate or inhibit the expression regulators of stem cell differentiation.