J. S. Weissman

CRISPRi screens identify the lncRNA, LOUP, as a multifunctional locus regulating macrophage differentiation epigenetically and inflammatory signaling through a short, encoded peptide

The paper uses CRISPRi screens to identify the lncRNA LOUP as a regulator of macrophage differentiation and inflammatory signaling through epigenetic and peptide-mediated mechanisms.

Graph-Dynamo: Learning stochastic cellular state transition dynamics from single cell data

This paper introduces Graph-Dynamo, a framework that learns stochastic cellular state transition dynamics from single cell data using graph-based methods and Fokker-Planck equations.

Triaging of -helical proteins to the mitochondrial outer membrane by distinct chaperone machinery based on substrate topology

The paper identifies distinct chaperone machinery for targeting mitochondrial outer membrane -helical proteins based on their topology using CRISPRi screens and biochemical analysis.

FET fusion oncoproteins disrupt physiologic DNA repair and create a targetable opportunity for ATR inhibitor therapy

This study shows FET fusion oncoproteins disrupt DNA repair by inhibiting ATM signaling, making ATR inhibitors a potential therapy for FET rearranged cancers.

Comparative landscape of genetic dependencies in human and chimpanzee stem cells

The paper compares genetic dependencies in human and chimpanzee stem cells, identifying 75 species-specific genes affecting cellular proliferation and supporting the G1-phase length hypothesis in human brain evolution.

MTCH2 is a mitochondrial outer membrane protein insertase

The paper identifies MTCH2 as an insertase required for mitochondrial TA protein insertion and shows its role in controlling TA localization and apoptosis sensitivity.

Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress

The paper shows that nucleotide depletion and DNA replication stress drive cell fate transitions in hematopoietic systems by activating lineage-specific maturation genes.

Lineage Recording Reveals the Phylodynamics, Plasticity and Paths of Tumor Evolution

The paper tracks tumor evolution in a mouse model using lineage tracing and single-cell RNA-seq, revealing plasticity, fitness-associated programs, and stereotypical evolutionary trajectories.

An engineered transcriptional reporter of protein localization identifies regulators of mitochondrial and ER membrane protein trafficking in high-throughput screens

The paper develops HiLITR, a tool to study protein trafficking by linking localization to reporter gene expression, and identifies genes affecting mitochondrial and ER membrane protein trafficking.

OpenCell: proteome-scale endogenous tagging enables the cartography of human cellular organization

The paper maps human protein localization and interactions using genome engineering, imaging, and data science, revealing functional communities and RNA-binding protein subgroups.

Single-cell lineages reveal the rates, routes, and drivers of metastasis in cancer xenografts

The paper uses single-cell lineage tracing and RNA-seq to identify diverse metastatic behaviors and their drivers in lung cancer xenografts in mice.

Genome-wide CRISPRi screening identifies OCIAD1 as a prohibitin client and regulatory determinant of mitochondrial Complex III assembly in human cells

BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2

This study identifies BRD2 as a regulator of ACE2 transcription and shows that BRD2 inhibitors block SARS-CoV-2 infection in human cells and animal models.

Selective Targeting of Ras Mutant Cancers via a New Small Molecule

This paper identifies 249C as a small molecule that selectively targets Ras-mutant cancers by inhibiting V-ATPase, disrupting lysosomal acidification and key survival pathways in Ras-driven tumors.

CRISPR-based functional genomics in human dendritic cells

This study develops a CRISPR/Cas9 method for human dendritic cells, enabling efficient gene knockouts and revealing mechanisms of immune response tuning to microbiome lipopolysaccharides.

Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients

The paper reveals the structural and mechanistic basis of EMC's role in biogenesis of distinct transmembrane proteins through cryo-EM structures and functional studies.

High-content Imaging-based Pooled CRISPR Screens in Mammalian Cells

The paper develops an imaging-based CRISPR screening method called optical enrichment to identify genes affecting nuclear size, identifying 14 hits from 6092 sgRNAs.

Pharmaceutical-grade Rigosertib is a Microtubule-destabilizing Agent

This paper shows pharmaceutical-grade rigosertib, with high purity, causes microtubule destabilization in cells, confirming its mechanism of action against cancer cells.

Conserved function of ether lipids and sphingolipids in the early secretory pathway

The paper identifies hypersensitive mutants in lipid biosynthesis and trafficking genes in sphingolipid-depleted cells and shows coordinate regulation of ether and sphingolipids.

The ER membrane protein complex is required to ensure correct topology and stable expression of flavivirus polyproteins

This study shows the ER membrane protein complex is essential for correct topology and stable expression of flavivirus polyproteins by preventing degradation of NS4A-NS4B.

Chaperone-Mediated Reflux of Secretory Proteins to the Cytosol During Endoplasmic Reticulum Stress

The paper identifies a chaperone-mediated process that refuxes properly folded ER proteins to the cytosol during ER stress, functioning parallel to ERAD.

Identification and characterization of a transporter complex responsible for the cytosolic entry of nitrogen-containing bisphosphonates

The paper identifies SLC37A3 as a transporter required for nitrogen-containing bisphosphonates (N-BPs) to enter the cytosol, revealing their mechanism of action.