J. G. Doench

Phenotypic screens identify biologic regulators of nanoparticle uptake in diffuse midline glioma

The paper identifies biologic regulators of nanoparticle uptake in diffuse midline glioma using CRISPR screens and functional assays, finding CTNNB1 and pathway members as key modulators.

Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer

This study identifies mSWI/SNF complex activity as a targetable dependency in POU2F3-positive small cell lung cancer, showing that inhibiting mSWI/SNF or BRD9 reduces tumor growth and improves survival.

Targetable leukemia dependency on noncanonical PI3Kγ signaling

This study identifies a targetable dependency on noncanonical PI3Kγ signaling in acute leukemias, showing that PI3Kγ inhibition with eganelisib improves survival when combined with cytarabine.

Vps18 contributes to phagosome membrane integrity in Mycobacterium tuberculosis-infected macrophages.

This study identifies Vps18 as a host factor critical for maintaining phagosomal membrane integrity in Mtb-infected macrophages, showing increased phagosomal damage and reduced antibiotic efficacy in its absence.

Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB

The paper identifies JADE3 as an antiviral activator of the NF-kB pathway through a CRISPR activation screen against influenza A virus.

Host metabolic pathways essential for malaria and related hemoparasites in the infection of nucleated cells

The paper identifies host metabolic pathways essential for malaria and related hemoparasites by combining a metabolic model and CRISPR screen.

High Density Domain-Focused CRISPR Screens Reveal Novel Epigenetic Regulators of HOX/MEIS Activation in Acute Myeloid Leukemia

The paper identifies SGF29 as a novel chromatin regulator of MEIS1 and AML oncogenes, showing its role in leukemogenesis and potential as a drug target.

Germline variation contributes to false negatives in CRISPR-based experiments with varying burden across ancestries

The paper identifies ancestry-related biases in CRISPR experiments caused by germline variants, showing disproportionate effects in cell models from recent African descent.

Molecular Basis for Interferon-mediated Pathogen Restriction in Human Cells

This study identifies RNF213 as essential for IFN-gamma-mediated restriction of intracellular pathogens like Toxoplasma gondii and Mycobacterium tuberculosis through ubiquitination, independent of autophagy.

ESCRT-dependent STING degradation curtails steady-state and cGAMP-induced signaling

The paper identifies an ESCRT complex that degrades STING to suppress its signaling, showing its role in maintaining immune homeostasis.

Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses

This study shows DYRK1A promotes viral entry of SARS-CoV, SARS-CoV-2, and MERS-CoV by regulating ACE2 and DPP4 transcription without its kinase activity.

A living biobank of canine mammary tumor organoids as a comparative model for human breast cancer

This study establishes a canine mammary tumor organoid biobank to model human breast cancer, showing genetic and phenotypic conservation and utility for drug testing and CRISPR screening.

Accounting for small variations in the tracrRNA sequence improves sgRNA activity predictions for CRISPR screening

This study improves sgRNA activity predictions by incorporating tracrRNA sequence variations, showing better performance than existing models on a new dataset.

Base editor scanning charts the DNMT3A activity landscape

The paper uses base editing and a DNA methylation reporter to scan DNMT3A mutations, identifying functional perturbations and revealing a noncanonical DNA affinity role for the PWWP domain.

Leukemia-intrinsic determinants of CAR-T response revealed by iterative in vivo genome-wide CRISPR screening.

This study identifies leukemia-intrinsic resistance mechanisms to CAR-T therapy through in vivo CRISPR screening in a murine B-ALL model, revealing IFNγ/JAK/STAT and antigen processing pathways as key mediators.

A Genome-wide CRISPR Screen Identifies WDFY3 as a Novel Regulator of Macrophage Efferocytosis

This study identifies WDFY3 as a novel regulator of macrophage efferocytosis through a genome-wide CRISPR screen, revealing its role in actin depolymerization and lysosomal acidification.

Regulation of Neuroendocrine Plasticity by the RNA-Binding Protein ZFP36L1

This study identifies ZFP36L1 as an LSD1 target gene that regulates neuroendocrine plasticity in SCLC by destabilizing mRNAs of lineage transcription factors.

A genetic screen identifies a protective type III interferon response to Cryptosporidium that requires TLR3 dependent recognition

This paper identifies a type III interferon response to Cryptosporidium requiring TLR3-dependent recognition, which protects against infection in mice.

Combinatorial G x G x E CRISPR screening and functional analysis highlights SLC25A39 in mitochondrial GSH transport

The paper uses CRISPR screening to identify gene-by-gene and gene-by-environment interactions among mitochondrial transporters, revealing SLC25A39's role in mitochondrial glutathione transport.

Bidirectional genome-wide CRISPR screens reveal host factors regulating SARS-CoV-2, MERS-CoV and seasonal coronaviruses

The paper performs bidirectional CRISPR screens to identify host factors regulating SARS-CoV-2, MERS-CoV, and seasonal coronaviruses, revealing new anti-viral proteins and general coronavirus cofactors.

Phosphate dysregulation via the XPR1:KIDINS220 protein complex is a therapeutic vulnerability in ovarian cancer

The paper identifies XPR1 and KIDINS220 as therapeutic targets in ovarian cancer by showing their role in phosphate dysregulation leading to cell death.

High-throughput CRISPR screens to dissect macrophage-Shigella interactions

This study uses CRISPR screens to identify host factors involved in Shigella-induced inflammation and macrophage survival, revealing potential therapeutic targets.

Illuminating host-mycobacterial interactions with functional genomic screening to inhibit mycobacterial pathogenesis

This study uses CRISPR screens to identify host genes that inhibit mycobacterial growth, revealing potential targets for host-directed tuberculosis therapies.

Non-oncology drugs are a source of previously unappreciated anti-cancer activity

The paper identifies non-oncology drugs with anti-cancer activity across 578 cancer cell lines using PRISM, finding that many drugs selectively inhibit cancer cells based on molecular features.

Agreement between two large pan-cancer CRISPR-Cas9 gene dependency datasets

This study compares two large pan-cancer CRISPR-Cas9 screens, finding high concordance in gene dependencies despite differences in protocols and reagents.

Identification of anti-norovirus genes in mouse and human cells using genome-wide CRISPR activation screening

This study identifies 57 host genes that inhibit murine norovirus replication in mouse or human cells using CRISPR activation screening, revealing novel antiviral mechanisms.