Hui Si Kwok

Pathway-wide base editing charts chemical-genetic interactions in MAPK signaling

This paper uses CRISPR base editing to map chemical-genetic interactions in the MAPK pathway, revealing drug resistance mechanisms and functional hotspots.

Proximity-induced rewiring of oncogenic kinase triggers apoptosis

This paper develops a small molecule, BRD8833, that induces BCR-ABL phosphorylation to disrupt its active site electric field, leading to loss of hyperactivity and apoptosis in BCR-ABL-dependent cancer cells.

A chemical-genetic interaction between PAF1 and ENL/AF9 YEATS inhibition

This study investigates the effects of ENL YEATS domain inhibitors in leukemia models, finding that suppression of ENL target genes is not sufficient to explain their anti-leukemia effects.

Coupling CRISPR Scanning with Targeted Chromatin Accessibility Profiling using a Double-Stranded DNA Deaminase

This paper introduces TDAC-seq, a method combining CRISPR perturbations with chromatin accessibility profiling to study cis-regulatory elements at single-nucleotide resolution.

Asymmetric Engagement of Dimeric CRL3KBTBD4 by the Molecular Glue UM171 Licenses Degradation of HDAC1/2 Complexes

This paper identifies UM171 as a molecular glue that promotes degradation of HDAC1/2 complexes by inducing asymmetric interactions between KBTBD4 and HDAC1.

KBTBD4 Cancer Hotspot Mutations Drive Neomorphic Degradation of HDAC1/2 Corepressor Complexes

This study identifies how KBTBD4 cancer mutations drive neomorphic interactions with HDAC1/2, leading to CoREST degradation and tumor growth, and shows potential therapeutic strategies.

Activity-based CRISPR Scanning Uncovers Allostery in DNA Methylation Maintenance Machinery

This study uses activity-based CRISPR scanning to identify allosteric sites in DNMT1 and UHRF1, revealing gain-of-function mutations that enhance DNA methylation activity.