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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.

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Diamond Blackfan anemia (DBA), a rare inherited bone marrow failure syndrome is typically treated with glucocorticoids that cause a host of often dangerous side effects. Using a mouse model, Whitehead scientists have determined that combining the drug fenofibrate with glucocorticoids could allow for dramatically lower steroid doses in the treatment of DBA and other erythropoietin-resistant anemias. These promising results are the foundation for a clinical trial that will begin soon.

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A novel approach that allows real-time imaging of the immune system’s response to the presence of tumors—without the need for blood draws or invasive biopsies—offers a potential breakthrough both in diagnostics and in the ability to monitor efficacy of cancer therapies.

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Candida albicans causes potentially lethal infections in immunocompromised individuals. Now, using a modified CRISPR-Cas system, Whitehead researchers can edit the fungus’s genome systematically—an approach that could help identify potential drug targets.

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A team of Whitehead Institute scientists has discovered that during division, stem cells distinguish between old and young mitochondria and allocate them disproportionately between daughter cells.

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Whitehead Institute scientists have for the first time identified a protein that appears to be a nutrient sensor for the key growth-regulating mTORC1 metabolic pathway.

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Long known for its ability to help organisms successfully adapt to environmentally stressful conditions, the highly conserved molecular chaperone heat-shock protein 90 (HSP90) also enables estrogen receptor-positive (ER+) breast cancers to develop resistance to hormonal therapy.

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Induced neural stem cells (iNSCs) hold promise for therapeutic transplantation, but their potential in this capacity has been limited by failed efforts to maintain such cells in their multi-potent NSC state. Now, Whitehead Institute scientists have created iNSCs that remain in the multi-potent state—without ongoing expression of reprogramming factors. This allows the iNSCs to self-renew repeatedly to generate cells in quantities sufficient for therapy.

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An exhaustive effort to sequence the mouse Y chromosome reveals a surprisingly large and complex biological beast, at the same time providing remarkable insight into a heated battle for supremacy between mammalian sex chromosomes.

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A team of Whitehead Institute scientists has discovered the surprising manner in which an enigmatic protein known as SUUR acts to control gene copy number during DNA replication. It’s a finding that could shed new light on the formation of fragile genomic regions associated with chromosomal abnormalities.

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Scientists have long theorized that the way in which the roughly three meters of DNA in a human cell is packaged to fit within a nuclear space just six microns wide, affects gene expression. Now, Whitehead Institute researchers present the first evidence that DNA structure does indeed have such effects—in this case finding a link between chromosome structure and the expression and repression of key genes.

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Cells rely on the mechanistic target of rapamycin complex 1 (mTORC1) pathway—which senses the availability of nutrients—to coordinate their growth with existing environmental conditions. The lab of Whitehead Member David Sabatini has identified a family of proteins that negatively regulate the branch upstream of mTORC1 that senses amino acids, the building blocks of proteins.

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Deploying sophisticated high-throughput sequencing technology, dubbed ψ-seq, a team of Whitehead Institute and Broad Institute researchers collaborated on a comprehensive, high-resolution mapping of ψ sites that confirms pseudouridylation, the most common post-transcriptional modification, does indeed occur naturally in mRNA.

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Induced pluripotent stem cells (iPSCs) can acquire serious genetic and epigenetic abnormalities that lower the cells’ quality and limit their therapeutic usefulness. Now Whitehead Institute researchers have identified a cocktail of reprogramming factors that produces very high quality iPSCs.

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Long associated with enabling the proliferation of cancer cells, the ancient cellular survival response regulated by Heat-Shock Factor 1 (HSF1) can also turn neighboring cells in their environment into co-conspirators that support malignant progression and metastasis. implications for the diagnosis, prognosis, and management of cancer patients.

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A team of Whitehead Institute researchers is bringing new levels of efficiency and accuracy to one of the most essential albeit tedious tasks of bench science: pipetting. Dubbed “iPipet,” the system converts an iPad or any tablet computer into a “smart bench” that guides the execution of complex pipetting protocols.

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Embryonic stem cell (ESC) research has been hampered by the inability to transfer research and tools from mouse ESC studies to their human counterparts, in part because human ESCs are “primed” and slightly less plastic than the mouse cells. Now researchers in the lab of Whitehead Institute Founding Member Rudolf Jaenisch have discovered how to manipulate and maintain human ESCs into a “naïve” or base pluripotent state similar to that of mouse ESCs without the use of any reprogramming factors.

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The protein CENP-A, which is integrated into human DNA at the centromere on each chromosome, has a vital role in cell division. Work from Whitehead Institute Member Iain Cheeseman’s lab describes how the vital and tightly controlled replenishment of CENP-A progresses.

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A signaling pathway once thought to have little if any role during embryogenesis is a key player in the formation of the front-most portion of developing vertebrate embryos. Moreover, signals emanating from this region—referred to as the “extreme anterior domain” (EAD)—orchestrate the complex choreography that gives rise to proper facial structure.

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Whitehead Institute scientists have genetically and enzymatically modified red blood cells to carry a range of valuable payloads—from drugs, to vaccines, to imaging agents—for delivery to specific sites throughout the body.