Ophir Shalem

SNX13 and SNX14 interorganelle tethers suppress lysosome membrane damage and neurodegeneration

This study identifies SNX13 and SNX14 as proteins that maintain lysosome membrane integrity and prevent neurodegeneration by supporting lipid homeostasis and repair mechanisms.

scRBP infers cell-specific RNA-binding protein regulons from single-cell transcriptomes at gene and isoform resolution

scRBP infers cell-specific RNA-binding protein regulons from single-cell transcriptomes, resolving targets at gene and isoform levels and linking genetic risk to disease.

Exploring transcriptomic and genomic latent variable correction approaches in differential expression analysis.

This paper evaluates combining expression-based surrogate variables and genotype-based principal components in differential expression analysis, finding the combined approach improves replicability and biological recall in ALS datasets.

CRISPR associated enzymes are mislocalized to the cytoplasm in iPSC-derived neurons resulting in KRAB-specific degradation

This study identifies that dCas9-KRAB mislocalizes to the cytoplasm in iPSC-derived neurons, leading to KRAB-specific degradation, and shows that adding a neuronal-specific NLS restores nuclear localization and expression.

Morphology-robust quantification of subcellular organization in complex cells

The paper introduces CellAligner, a framework to robustly compare subcellular protein organization across morphologically distinct cells, improving classification accuracy in neuronal imaging.

Tau Aggregation Results in an Impaired Ability to Counteract Microtubule Destabilization via Specific Combinatorial Tau Phosphorylation Patterns

This study shows that tau phosphorylation patterns influence microtubule stability, with specific phosphorylations impairing tau's ability to counteract destabilization, suggesting phosphorylation may respond to, rather than precede, MT instability.

Intracellular Protein Editing to Enable Incorporation of Non-Canonical Residues into Endogenous Proteins

This paper introduces a protein editing technology that enables site-specific insertion of non-canonical residues into endogenous proteins in live mammalian cells.

CRISPR screen for rAAV production implicates genes associated with infection

The paper uses a CRISPR screen to identify genes affecting rAAV production in HEK 293 cells, finding that heparan sulfate biosynthesis and vesicular trafficking genes influence yield.

High-throughput optimized prime editing mediated endogenous protein tagging for pooled imaging of protein localization

This paper develops a prime editing-based method for pooled endogenous protein tagging and imaging, enabling scalable analysis of subcellular protein localization patterns.

Antisense oligonucleotide depletion of CCDC146 is a broad-spectrum therapeutic strategy for ALS

The paper identifies CCDC146 as a modifier of ALS survival through primary cilia dysfunction and shows ASO targeting of CCDC146 rescues ALS phenotypes in human and mouse models.

The SMC5/6 complex is required for maintenance of genome integrity upon APOBEC3A-mediated replication stress

This study identifies the SMC5/6 complex as essential for genome stability in cells with active APOBEC3A, showing that its loss leads to increased DNA damage and replication stress.

High density SNP array and reanalysis of genome sequencing uncovers CNVs associated with neurodevelopmental disorders in KOLF2.1J iPSCs

The paper identifies CNVs in KOLF2.1J iPSCs linked to neurological disorders, showing they arose in vitro and affect gene expression in neural cells.

Cell environment shapes TDP-43 function: implications in neuronal and muscle disease

The paper compares TDP-43's transcriptional and splicing effects in muscle and neuronal cells, showing tissue-specific roles in disease.

Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia

The paper uses unsupervised machine learning to identify three molecular subtypes in ALS cortex samples, associated with oxidative stress, retrotransposon activation, and glial activation.

Integrated design, execution, and analysis of arrayed and pooled CRISPR genome editing experiments

The paper presents a protocol for designing, executing, and analyzing CRISPR genome editing experiments using CRISPOR and CRISPResso.

High-resolution interrogation of functional elements in the noncoding genome

This paper uses a CRISPR screen to identify noncoding genomic elements that influence drug resistance in melanoma cells.

Improved vectors and genome-wide libraries for CRISPR screening

The paper introduces improved CRISPR screening vectors and libraries to enhance genome-wide loss-of-function studies in human and mouse cells.