Jay Shendure

The paper introduces OPTIMuS PRIME-Del, a CRISPR-based method for multiplexed, precise deletion of cis-regulatory elements, validated through molecular tagging and scRNA-seq analysis.

The paper identifies chromatin-opening transcription factors in mouse embryonic stem cells using CRISPRa screens, revealing autonomous, opportunistic, and hierarchical mechanisms.

A prime-editing recorder in one mouse embryo yields a dated, zygote-rooted lineage tree of 1.28M cells at E13.5, enabling clonal dominance, sibling-fate and cell-type coupling analyses.

This paper reconstructs whole-organism cell phylogenies with resolved ancestral transcriptional states in zebrafish larvae using a novel computational framework called LEAP.

The paper introduces LAMPRAs to measure how cis-regulatory element composition affects gene expression using synthetic loci.

The paper characterizes regulatory variants in human neurons using lentiMPRA and shows that variant effects are influenced by regulatory element activity and sequence context, not population frequency.

SciPhy estimates time-scaled phylogenies and cell population parameters from sequential genetic lineage tracing data using a Bayesian framework, showing improved accuracy over existing methods.

This paper introduces Shred-seq, a method to scan large-scale deletions in the human genome, revealing essential regions including noncoding sequences and establishing a lower bound for viability.

The paper develops STEAM, an evolution-augmented deep learning model, to predict mammalian enhancer landscapes across species using comparative genomics and single-cell data.

The paper presents a barcoded multiplex strategy to screen enhancer AAVs using single-cell RNA sequencing and taxonomy mapping, but finds significant technical and biological noise complicates accurate expression pattern analysis.

This paper demonstrates that AI-designed receptor modulators can drive efficient human fibroblast-to-muscle transdifferentiation by rewiring extracellular signaling.

The paper systematically perturbs enhancer sequences to study their functional properties and robustness, revealing insights into regulatory sequence space and enhancer activity.

The paper studies the evolutionary changes of mammalian enhancers by analyzing orthologous sequences across multiple species and using deep learning to model functional changes.

This paper uses topic modeling to identify developmental states in medulloblastoma subtypes across multiple datasets and technologies.

The paper identifies active human neural enhancers and CRISPRa gRNAs that upregulate NDD risk genes, providing a resource for cis-regulatory therapy development.

This study profiles 5.3 million cells from 55 rhesus macaques across their lifespan to map age-related changes in brain cell types and identify molecular signatures linked to aging and Alzheimer's disease.

The paper develops a method to discover new effector handles for proteome editing by combining de novo protein design with multiplex screening, identifying handles for degradation and stabilization of target proteins.

The paper describes a method to generate human embryo-like structures by pre-patterning stem cells and mixing them, resulting in models with extended anterior-posterior organization and neural features.

The paper identifies 545 expression-modulating variants in CD4+ T cells linked to autoimmune diseases and shows they regulate genes in a lymphocyte activation network.

This paper introduces ccMPRA, a method that combines Capture-C and MPRA to study promoter interactions and regulatory activity, identifying enhancers and silencers.

The paper develops monoclonal gastruloids from single mouse embryonic stem cells and uses DNA Typewriter to reveal heritable lineage biases in early development.

The paper develops monoclonal embryoids with genetic barcoding to overcome clonal complexity bottlenecks in mosaic organoid screens, enabling more accurate quantification of genetic perturbation effects.

The paper introduces Icebear, a neural network framework for cross-species imputation and comparison of single-cell transcriptomic profiles, revealing evolutionary adaptations of X-chromosome upregulation in mammals.

This paper introduces P3 editing, a method that links protein-protein proximity to CRISPR-Cas9 dual-component guide RNA formation, enabling genome editing triggered by molecular interactions in human cells.

This paper introduces Genome-Shuffle-seq, a method for generating and mapping structural variants in mammalian genomes, and demonstrates its application in mouse embryonic stem cells.

The paper identifies functional cis-regulatory elements in three human cell types using lentiMPRAs and develops predictive models for CRE function.

The paper shows that AAV libraries packaged as pools exhibit extensive chimerism due to length and homology dependence, affecting most genomes.

The paper designs and characterizes diverse genomic parts for precise genome editing and molecular recording in mammalian cells.

The paper describes a CRISPRa screening method combining multiplex perturbations with sc-RNA-seq to identify cell-type-specific regulatory elements and their target genes.

The paper shows that leukemia cells secrete apelin, which promotes clonal expansion of niche endothelial cells and drives leukemogenesis in zebrafish.