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Many questions on the activity of the Ras proto-oncogene are unanswered due to the lack of tools for detecting active Ras in living cells. Here, we used protein design and structure prediction algorithms to develop biosensors that detect the activity and environment of endogenous Ras.
Mapping higher-order RNA structures and intermolecular RNA–RNA interactions throughout the transcriptome is critical for understanding RNA functions. We developed KARR-seq, a chemical-assisted RNA proximity capture and sequencing technology that enables sensitive and accurate detection of the RNA structurome and functional RNA–RNA interactions.
An integrated wearable and wireless ultrasound device enables the continuous monitoring of physiological information from tissues in moving individuals.
Expression profiles of single live cells are generated from Raman microscopy using deep learning, enabling us to track expression dynamics along cell reprogramming or differentiation.
We developed synthetic serum markers that can be expressed in the brain but are transported into the blood, enabling minimally invasive monitoring of gene expression in the brain with a simple blood test.
Repetitive DNA sequences known as tandem repeats (TRs) are linked to dozens of monogenic diseases and to cancer. We developed a computational method to characterize TRs using PacBio HiFi sequencing. This software can be used to discover and profile pathogenic repeat expansions and to catalog genetic and epigenetic variation in TR regions.
Chimeric antigen receptor (CAR) T cells in the solid tumor microenvironment enter a partially dysfunctional state called T cell exhaustion. Interleukin (IL)-10-producing CAR T cells retain their metabolic fitness, resist T cell exhaustion and display unprecedented antitumor activity indicated by high cure rates and durable responses in mice. Clinical studies of IL-10-producing CAR T cells are underway.
pA regulator is an RNA-based, non-immunogenic regulation system of gene expression that achieves up to 900-fold induction by using an inducer drug within the clinically safe dose range.
We developed luciferase-based splicing reporters to evaluate 718 RNA-binding proteins (RBPs) for the ability to activate exon inclusion. Our screen detected RBPs with no previously characterized roles in splicing and utilized RBP domains displaying potent exon activation to develop programmable splicing modulators with improved strength, generalizability and size over previous versions.
The protracted timeline of maturation is a major bottleneck in generating adult-like neurons from human pluripotent stem cells. We identify a combination of four chemicals that promotes neuronal maturation by repressing epigenetic factors that inhibit it and stimulating activity-dependent factors that promote it.
Thousands of cellular mRNAs contain the methyl modification m6A, which plays critical roles in mRNA processing and gene expression. We developed GEMS, a genetically encoded m6A sensor that provides a simple readout for m6A methylation in living cells and offers a platform for achieving m6A-coupled effector protein expression.
Two DNA nanodevices, RatiNa and pHlicker, provide precise mapping of sodium levels in acidic organelles and potassium activity at a single-organelle resolution.
