Journal ArticleSLAS discovery : advancing life sciences R & D · June 2023
We report a comprehensive drug synergy study in acute myeloid leukemia (AML). In this work, we investigate a panel of cell lines spanning both MLL-rearranged and non-rearranged subtypes. The work comprises a resource for the community, with many synergisti ...
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Journal ArticleACS chemical biology · April 2023
Gene transcription does not only require writers of active histone modifications; on-site opposition by erasers is essential for many genes. Here, we propose the concept of dynamic opposition of histone modifications to explain this conundrum. We highlight ...
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Journal ArticleTrends in biotechnology · March 2023
Enhanced ascorbate peroxidase 2 (APEX2) is a protein generated with directed evolution by Lam et al. that has transformed our understanding of subcellular entities and phenomena. The rapid kinetics of this engineered protein highlights the power of directe ...
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Journal ArticleNature biotechnology · April 2022
The ability to control translation of endogenous or exogenous RNAs in eukaryotic cells would facilitate a variety of biotechnological applications. Current strategies are limited by low fold changes in transgene output and the size of trigger RNAs (trRNAs) ...
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Journal ArticleNature methods · January 2022
Evolution occurs when selective pressures from the environment shape inherited variation over time. Within the laboratory, evolution is commonly used to engineer proteins and RNA, but experimental constraints have limited the ability to reproducibly and re ...
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Journal ArticleMolecular systems biology · March 2021
Our understanding of complex living systems is limited by our capacity to perform experiments in high throughput. While robotic systems have automated many traditional hand-pipetting protocols, software limitations have precluded more advanced maneuvers re ...
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Journal ArticleACS chemical biology · June 2020
SWI/SNF (BAF) complexes are a diverse family of ATP-dependent chromatin remodelers produced by combinatorial assembly that are mutated in and thought to contribute to 20% of human cancers and a large number of neurologic diseases. The gene-activating funct ...
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Journal ArticleCell · February 2020
Due to the rapid emergence of antibiotic-resistant bacteria, there is a growing need to discover new antibiotics. To address this challenge, we trained a deep neural network capable of predicting molecules with antibacterial activity. We performed predicti ...
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Journal ArticleMolecular cell · January 2019
Recent studies have indicated that nucleosome turnover is rapid, occurring several times per cell cycle. To access the effect of nucleosome turnover on the epigenetic landscape, we investigated H3K79 methylation, which is produced by a single methyltransfe ...
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Journal ArticleScience (New York, N.Y.) · March 2018
Proximity, or the physical closeness of molecules, is a pervasive regulatory mechanism in biology. For example, most posttranslational modifications such as phosphorylation, methylation, and acetylation promote proximity of molecules to play deterministic ...
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Journal ArticleNature communications · September 2017
Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to s ...
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Journal ArticleNature genetics · February 2017
The opposition between Polycomb repressive complexes (PRCs) and BAF (mSWI/SNF) complexes has a critical role in both development and disease. Mutations in the genes encoding BAF subunits contribute to more than 20% of human malignancies, yet the underlying ...
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Journal ArticleACS chemical biology · March 2015
The DOT1L lysine methyltransferase has emerged as a validated therapeutic target in MLL-rearranged (MLLr) acute leukemias. Although S-adenosylmethionine competitive inhibitors have demonstrated pharmacological proof-of-principle in MLLr-leukemia, these com ...
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Journal ArticlePloS one · January 2013
Adhesion-based microfluidic cell separation has proven to be very useful in applications ranging from cancer diagnostics to tissue engineering. This process involves functionalizing microchannel surfaces with a capture molecule. High specificity and purity ...
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Journal ArticleLab on a chip · September 2012
To isolate clinically and biologically relevant cell types from a heterogeneous population, fluorescent or magnetic tagging together with knowledge of surface biomarker profiles represents the state of the art. To date, it remains exceedingly difficult to ...
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Journal ArticleNature communications · January 2012
Selective inhibition of protein methyltransferases is a promising new approach to drug discovery. An attractive strategy towards this goal is the development of compounds that selectively inhibit binding of the cofactor, S-adenosylmethionine, within specif ...
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