Lars Michael Steinmetz

Time-resolved single-cell screening reveals the dynamic regulatory architecture of human cardiogenesis

This study uses time-resolved single-cell CRISPR screening and a multiome atlas to uncover dynamic gene regulatory networks in human cardiogenesis, identifying stage-specific regulators and CHD-linked gene functions.

PHAROS: turning single-cell perturbation models into target-directed drug-combination screens

PHAROS uses a pretrained single-cell perturbation model to predict and prioritize effective drug combinations without retraining, showing success in cell lines and patient-derived tumors.

Image-based transposon screening reveals a flavin reductase that restrains intracellular Salmonella replication in macrophages

The paper uses image-based transposon screening to identify a flavin reductase that promotes Salmonella replication in macrophages by reducing oxidative and nitrosative stress.

Nuclear size is genetically controlled and influences cell fate

The paper identifies regulators of nuclear-to-cell size ratio and shows nuclear size influences gene expression and cell fate.

Cell organization and disturbance-mapping using image activated cell-profiling (CODIAC)

CODIAC profiles spatial protein localization and abundance changes using image-enabled sorting and machine learning, detecting perturbation effects on the spatial proteome.

Mapping enhancer-gene regulatory interactions from single-cell data

The paper introduces scE2G models to predict enhancer-gene regulatory interactions from single-cell data and demonstrates their performance across multiple cell types and perturbations.

Damaging RBM20 E-rich domain variants are not rescued by gene replacement

The paper investigates E-rich domain variants of RBM20, showing they reduce protein abundance and cause splicing defects, but are not rescued by RBM20 overexpression.

Study design and rationale of Boxed-Breathing-Heart: a translational ex vivo study evaluating virus-mediated gene delivery for gene therapy in normothermic machine-perfused human hearts

The paper describes an ex vivo study using normothermic machine-perfused human hearts to evaluate AAV-mediated gene delivery for cardiac gene therapy.

Ubiquitin selective ribosome profiling reveals systematic principles of co-translational quality control

The paper introduces UbSeRP to map co-translational ubiquitination across the translatome, revealing RQC substrates, biophysical features predicting RQC, and aging-related changes in CTU.

Multimodal phenotyping defines variant-to-function maps for RBM20 in dilated cardiomyopathy

The paper develops a deep mutational scanning framework to map variants to molecular functions in RBM20, identifying functional hotspots and therapeutic strategies for dilated cardiomyopathy.

PerturbPlan: An analytical framework for designing Perturb-seq experiments

PerturbPlan provides an analytical framework to design single-cell CRISPR screens by calculating statistical power and enabling interactive experiment planning.

Disruption of RBM20 causes atrial electrophysiological disturbances

This study examines the effects of RBM20-R636Q mutation on atrial electrophysiology and evaluates SGLT inhibitors as potential therapeutics for atrial remodeling and arrhythmias.

Genome-scale mapping of variant, enhancer and gene function in primary human CD4+ T cells

The paper maps variant, enhancer, and gene function in primary human CD4+ T cells by combining Perturb-seq of regulatory elements and genes, identifying CRE-gene pairs and linking variants to disease-related programs.

Sarcomeric Remodelling in Human Heart Failure unraveled by single molecule long read sequencing

The paper uses single molecule long-read sequencing to analyze transcriptomes in heart failure patients and controls, identifying novel isoforms and convergent isoform changes across different cardiomyopathy types.

Improved cloning-free one-step CRISPR-Cas12a-assisted tagging of mammalian genes using PCR generated reagents (PCR tagging)

The paper improves CRISPR-Cas12a-assisted gene tagging in mammalian cells by enhancing HDR efficiency and reducing off-target integrations through modified cassettes and repair pathway modulation.

Innate immune responses to Plasmodium falciparum disrupt the blood-brain barrier

The paper investigates how innate immune responses to Plasmodium falciparum contribute to blood-brain barrier disruption in cerebral malaria using an in vitro model.

A systematic survey of distal element-gene regulatory interactions with Direct-Capture Targeted Perturb-seq

This study identifies most distal element-gene interactions have small effect sizes (<10%) using DC-TAP-seq, revealing limitations in prior CRISPR screens and suggesting new model requirements.

Mutational scanning by multiplexed genome editing of the essential transcription termination factor Nrd1.

The paper develops a CRISPR-based platform to scan mutations in essential genes, applying it to Nrd1 to identify critical residues in its CTD-interacting domain.

Enhancer-targeting CRISPR screens at coronary artery disease loci suggest shared mechanisms of disease risk

The paper identifies causal genetic mechanisms at CAD GWAS loci using CRISPR screens and chromatin analysis, revealing enhancer-gene links and ancestry/sex-specific risk factors.

Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model

This study shows that Plasmodium falciparum egress products disrupt BBB endothelial junctions and activate JAK-STAT signaling, leading to increased permeability and suggesting therapeutic targets.

CAMK2D causes heart failure in RBM20 cardiomyopathy

This study identifies CAMK2D overactivation as the cause of heart failure in RBM20 cardiomyopathy and shows pharmacological inhibition can reverse cardiac dysfunction.

Somatic epimutations enable single-cell lineage tracing in native hematopoiesis across the murine and human lifespan

This paper introduces EPI-clone, a method using DNA methylation to trace clonal lineages in hematopoiesis without genetic engineering, showing clonal complexity declines with age in mice and expands in humans.

A CRISPR/Cas9-based enhancement of high-throughput single-cell transcriptomics

The paper introduces scCLEAN, a CRISPR/Cas9-based method to enhance single-cell transcriptomics by improving library complexity and isoform detection.

Perturbation-driven transcriptional heterogeneity impacts cell fitness

The paper maps cellular states in yeast using a single-cell transcriptome atlas generated from genetic perturbations and identifies regulators of transcriptional heterogeneity.

Cohesin-mediated 3D contacts tune enhancer-promoter regulation

This study uses CRUDO to show that cohesin and 3D contacts influence enhancer-promoter regulation, with distal enhancers showing stronger cohesin dependence.

Functional phenotyping of genomic variants using multiomic scDNA-scRNA-seq

This paper introduces SDR-seq, a multiomic scDNA-scRNA-seq method to link genotypes with gene expression, showing variants affect expression in iPSCs and B-cell lymphoma.

Genome-scale analysis of interactions between genetic perturbations and natural variation

The paper identifies gene-perturbation interactions across genetic backgrounds in yeast using CRISPRi and combinatorial DNA barcode sequencing, revealing 460 genes with variable effects and 234 interacting loci.

Dissecting quantitative trait nucleotides by saturation genome editing

The paper develops MAGESTIC 3.0, a CRISPR-based system for genome-wide variant installation in yeast, revealing missense variants and multiple causal variants in quantitative trait loci across environmental conditions.

Integration of genetic and epigenetic data pinpoints autoimmune specific remodelling of enhancer landscape in CD4+ T cells

The paper integrates genetic and epigenetic data to identify autoimmune-specific enhancer dysregulation in CD4+ T cells and its role in disease pathogenesis.

An encyclopedia of enhancer-gene regulatory interactions in the human genome

ENCODE-rE2G, a classifier trained on K562 CRISPR perturbations, maps 13,455,443 enhancer-gene interactions across 352 biosamples, matching or exceeding prior models on CRISPR, eQTL, and GWAS benchmarks.