Brian B. Liau

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.

Systematic Targeting of Protein Complexes with Molecular COUPLrs

The paper introduces molecular COUPLrs to systematically target protein complexes, identifying new glue classes and their interactions in cancer cell lines.

Oxidized protein states define metastatic fitness in lung cancer

The paper identifies oxidative protein states as drivers of metastatic fitness in lung cancer by linking ROS-regulated protein modifications to mitochondrial function and metastasis.

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.

Genetic landscape of DNMT3A R882H reveals mechanism of aberrant oligomerization

This study identifies two mechanisms that rescue DNMT3A R882H activity by analyzing combinatorial mutations and showing R882H promotes aberrant oligomerization.

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.

DNA methylation insulates genic regions from CTCF loops near nuclear speckles

The paper investigates how DNA methylation affects CTCF-mediated chromatin loops and gene expression by using DNMT1 inhibition and targeted protein degradation.

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.

DrugMap: A quantitative pan-cancer analysis of cysteine ligandability

DrugMap quantitatively analyzes cysteine ligandability across 416 cancer cell lines, revealing redox state, conformational changes, and mutations as drivers of variability, and identifies covalent inhibitors targeting NFκB1 and SOX10.

CTCF/cohesin organize the ground state of chromatin-nuclear speckle association

This study identifies CTCF and cohesin as essential for chromatin-nuclear speckle association, showing their role in gene inducibility and relevance to disease.

Identification of chemotherapy targets reveals a nucleus-to-mitochondria ROS sensing pathway

The paper identifies a nucleus-to-mitochondria ROS sensing pathway involving CHK1 and SSBP1 that mediates resistance to platinum-based chemotherapies in ovarian cancers.

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.

Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery

The paper develops LIMe-Hi-C to study how Polycomb repressive complex 2 and lamina association regulate heterochromatin sub-compartments.

Profiling the Landscape of Drug Resistance Mutations in Neosubstrates to Molecular Glue Degraders

This study identifies drug resistance mutations in neosubstrates of molecular glue degraders using CRISPR-suppressor scanning and reveals common resistance mechanisms.