Jacob E. Corn

Proximity determines donor candidacy during DNA double-stranded break homology directed repair

The paper develops RaPID-seq to study homology search during HDR and finds that DSB proximity determines template candidacy, with distant sequences not efficiently searched despite sequence identity.

Epithelial-Mesenchymal Transition Induces FAM134A-mediated ER-phagy to Regulate Procollagen Secretion

The paper shows that EMT activates ER-phagy to regulate procollagen secretion, with FAM134A uniquely mediating this process through a non-canonical mechanism.

Directed evolution of compact RNA-guided nucleases for enhanced activity in mammalian cells

The paper improves the activity of compact RNA-guided nucleases in mammalian cells through directed evolution, resulting in variants with higher editing efficiency and reduced off-target effects.

Predicting cellular functions of human phosphosites

The paper develops predictors to functionally characterize human phosphosites using integrated data, revealing novel functions and connections to DNA repair and cell survival.

SP110 sequestration of SP100 protects against toxic filaments during innate immune signaling

The paper identifies SP110 as a negative regulator of type 1 interferon-driven cell death by counteracting SP100's toxic filament formation through CARD domain interactions.

DCLRE1A orchestrates CAG repeat contraction following Cas12a-induced DNA breaks

This study identifies DCLRE1A as a key factor in CAG repeat contraction following Cas12a-induced DNA breaks and demonstrates its role in enhancing repeat shortening through interactions with repair proteins.

Cis-Regulatory Element and Transcription Factor Circuitry Required for Cell-Type Specific Expression of FOXP3

The paper identifies cis-regulatory elements and transcription factors controlling FOXP3 expression in human Tregs and Tconvs, revealing mechanisms that restrict FOXP3 to Tregs in mice.

Cell-stereotyped DNA repair outcomes are widespread during genome editing

The paper develops scOUT-seq to profile DNA repair outcomes in single cells and finds that repair outcomes vary significantly across cell types and subtypes.

WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2

This study shows WEE1 inhibitors work better with mRNA translation defects by activating GCN2, and suggests ways to reduce off-target effects.

Disruption of nucleolar integrity triggers cellular quiescence through organelle rewiring and secretion

This study identifies a stress response pathway linking nucleolar disruption to cellular quiescence and secretion, revealing its role in cancer progression.

Single-stranded HDR templates with truncated Cas12a binding sequences improve knock-in efficiencies in primary human T cells

This study improves CRISPR-Cas12a knock-in efficiency in human T cells by using single-stranded DNA templates with double-stranded Cas-target-sequences, achieving up to 90% knock-in rates for transgene inserts.

CCAR1 promotes DNA repair via an unanticipated role in alternative splicing

The paper identifies CCAR1 as a splicing fidelity factor that regulates alternative splicing of FANCA and other genes, impacting DNA repair processes.

Engineering of the Endogenous HBD promoter increases HbA2

This study uses CRISPR-Cas9 to edit the endogenous {delta}-globin promoter to increase HbA2 expression in human erythroid cells, showing that multiple transcription factor elements are required for effective upregulation.

TREX1 restricts CRISPR-Cas9 genome editing in human cells

The paper identifies TREX1 as a suppressor of CRISPR-Cas9 HDR efficiency in human cells and shows that TREX1 removal or use of chemically protected templates can enhance HDR.

Adenine base editing is an efficient approach to restore function in FA patient cells without double-stranded DNA breaks

This study demonstrates that adenine base editing can restore FANCA function in FA patient cells without causing DNA breaks, showing promise for therapeutic applications.

Identification of novel HPFH-like mutations by CRISPR base editing that elevates the expression of fetal hemoglobin

This study uses CRISPR base editing to identify novel mutations in the HBG promoter that increase fetal hemoglobin expression without harmful effects.

Suppression of unwanted CRISPR/Cas9 editing by co-administration of catalytically inactivating truncated guide RNAs

This paper introduces dead-RNAs (dRNAs) to suppress unwanted CRISPR/Cas9 off-target and HDR-corrected site cleavage, enabling precise genome editing.

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair

The paper identifies CDC7 inhibition as a method to enhance HDR efficiency in CRISPR-Cas9 gene editing by inducing an early S-phase cell cycle arrest.

ATF4 mediates fetal globin upregulation in response to reduced β-globin

The paper identifies ATF4 as a key regulator of fetal globin re-expression in response to reduced β-globin, providing mechanistic insight into stress-induced globin compensation.

Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq

This paper introduces DISCOVER-Seq, a method to detect CRISPR off-targets in vivo with single-base resolution, applicable to multiple Cas nucleases.

CRISPR-Cas9 interrogation of a putative fetal globin repressor in human erythroid cells.

This study uses CRISPR-Cas9 to test a putative fetal globin repressor region, finding it does not autonomously silence gamma-globin, suggesting it is not a therapeutic target for beta-hemoglobinopathies.

High-level correction of the sickle mutation amplified in vivo during erythroid differentiation

Cas9-mediated correction of the sickle mutation in human hematopoietic stem cells achieves curative levels of editing.

Double Stranded DNA Damage and Genome Editing Trigger Ribosome Remodeling and Translational Shutdown

This study shows that DNA double-strand breaks cause ribosome remodeling and translational shutdown, independent of p53 and preceding transcriptional changes.

Enhancer connectome in primary human cells reveals target genes of disease-associated DNA elements

This paper uses HiChIP to map enhancer-promoter interactions in primary human cells, linking disease-associated DNA variants to their target genes.

CRISPR-Cas9 Genome Editing In Human Cells Works Via The Fanconi Anemia Pathway

This study identifies the Fanconi Anemia pathway as essential for single-stranded template repair in CRISPR-Cas9 genome editing, distinguishing it from double-stranded donor repair.

Discovery of an autoimmunity-associated IL2RA enhancer by unbiased targeting of transcriptional activation

The paper identifies an IL2RA enhancer associated with autoimmunity using CRISPRa and shows it affects gene activation timing without blocking expression.

Efficient Correction of the Sickle Mutation in Human Hematopoietic Stem Cells Using a Cas9 Ribonucleoprotein Complex

This study corrects the sickle mutation in human hematopoietic stem cells using a Cas9 RNP/ssDNA donor approach, showing long-term therapeutic editing in mice.