Michael Boutros

TCF4 and CtBP1 Repress LEF1 to Maintain a TCF4-centric Transcriptional Program in Colon Cancer.

This study shows TCF4 represses LEF1 to maintain a TCF4-driven transcriptional program in colon cancer, with TCF4 regulating MYC and cell cycle while repressing LEF1's immune-related effects.

WNT-driven immune evasion promotes malignant transformation of BRAF-mutant colorectal cancer

This study shows that WNT signaling enables immune evasion in BRAF-mutant colorectal cancer, promoting tumor progression through changes in T cell phenotypes.

Multi-omics, organoid-based modeling reveals an SRC/mTOR-dependent fetal-like stem cell trajectory in colorectal cancer

The paper identifies a fetal-like stem cell trajectory in colorectal cancer using multi-omics and organoid models, linked to poor prognosis and SRC/mTOR dependency.

Proliferation and differentiation of intestinal stem cells depends on the zinc finger transcription factor BCL11/Chronophage

This study identifies Cph as a key regulator of intestinal stem cell proliferation and differentiation, showing its role in maintaining ISC and EE populations and remodeling progenitor transcriptomes.

Direct detection of CRISPR mutations and transcriptional responses at single cell resolution in vivo

This paper introduces scPT-seq, a method to detect CRISPR mutations and transcriptional responses at single-cell resolution in vivo, revealing clonal markers and lineage dynamics in Drosophila intestine.

Wnt10b signaling regulates replication stress-induced chromosomal instability in human cancer

This study shows Wnt10b signaling prevents replication stress-induced chromosomal instability in cancer cells by suppressing microtubule dynamics and chromosome missegregation.

An organoid platform reveals MEK-PARP co-targeting to enhance radiation response in rectal cancer

The paper uses a patient-derived rectal cancer organoid platform to identify MEK and PARP inhibitors that synergize with radiation to enhance treatment response in locally advanced rectal cancer.

Molecular recording of cellular protein kinase activity with chemical labeling

The paper introduces molecular recorders to track kinase activity in cells and applies them to study PKA activity and neuromodulation.

Secretion and signaling properties of Wnt11 and Wnt3 are determined by their N-terminus

This study shows that the N-terminus of Wnt proteins determines their secretion and signaling properties, with Wnt11's N-terminus enabling Evi/Wls-independent secretion and Frizzled 6 activation.

MEK inhibition induces AXIN1 loss in colorectal cancer by mTOR associated suppression of protein synthesis

This study shows MEK1/2 inhibitors reduce AXIN1 levels in CRC by mTOR-dependent translational repression, not by affecting protein stability.

Class III PI3K is essential for Wingless secretion and Evi/Wls recycling in Drosophila

The paper identifies Vps15 as essential for endocytosis-dependent Wg secretion and reveals divergent post-endocytic fates of Wg and Evi/Wls in Drosophila.

Shape stabilization in budding intestinal organoids by geometrical ratcheting

This study uses 3D reconstructions and simulations to show that geometrical ratcheting stabilizes the shape of budding intestinal organoids through changes in tension and actomyosin reorganization.

Image-based screens identify regulators of endogenous Dvl2 biomolecular condensates

The paper identifies regulators of Dvl2 biomolecular condensates using image-based screens and phosphoproteomics, finding CK1δ/ε inhibition blocks condensate formation and modulates Wnt signaling.

Enhanced in vivo gene knockout with undetectable off-targets using multiplexed Cas12a sgRNAs

The paper presents a Cas12a-based system using multiplexed sgRNAs to achieve efficient and specific gene knockouts in Drosophila with minimal off-target effects.

Restraining Wnt activation and intestinal tumorigenesis by a Rab35 dependent GTPase relay

This study identifies Rab35 as a tumor suppressor that modulates Wnt signaling through a GTPase relay, highlighting its role in restraining intestinal tumorigenesis.

Epithelial cells of the intestine acquire cell-intrinsic inflammation signatures during ageing

This study shows that aged intestinal epithelial cells exhibit a persistent inflammation signature, marked by MHC class II upregulation and increased chromatin accessibility of inflammation-associated loci.

Glyoxal as alternative fixative for single cell RNA sequencing

This study develops and benchmarks glyoxal as a fixative for scRNA-seq, showing it preserves transcriptomes in Drosophila and human cells with high correlation to unfixed samples.

The pleiotropic functions of Pri smORF peptides synchronise leg development regulators

The paper identifies Pri smORF peptides as pleiotropic regulators of leg development in Drosophila, functioning through Ubr3-dependent and -independent mechanisms in patterning and cell survival.

A temperature-tolerant CRISPR base editor mediates highly efficient and precise gene inactivation in vivo

This paper develops a temperature-tolerant CRISPR base editor for efficient and precise gene inactivation in Drosophila, showing high efficiency and minimal byproducts.

The drug-induced phenotypic landscape of colorectal cancer organoids

This study uses image-based profiling and multi-omics integration to identify morphological axes of variation in colorectal cancer organoids and link them to biological mechanisms and drug responses.

Pooled CRISPR screening at high sensitivity with an empirically designed sgRNA library

This study designs an empirically optimized sgRNA library and experimental protocol to enhance the sensitivity and dynamic range of CRISPR screens for gene essentiality.

Multiplexed conditional genome editing with Cas12a in Drosophila

This paper demonstrates efficient Cas12a-based gene editing in Drosophila, enabling temperature-controlled editing, multiplex targeting, and cell-type-specific manipulation.

Allele-specific endogenous tagging and quantitative analysis of beta-catenin in colorectal cancer cells

This study uses genome engineering to fluorescently tag wild-type and mutant beta-catenin alleles in colorectal cancer cells, revealing distinct biophysical properties and showing how Wnt signaling modulates wild-type behavior to resemble the mutant form.

JNK-dependent intestinal barrier failure disrupts host-microbe homeostasis during tumorigenesis

This study shows that JNK signaling disruption in intestinal tumors leads to barrier failure and microbiome imbalance, which can be reversed by JNK inhibition or microbiome depletion.

Modelling asymmetric count ratios in CRISPR screens to decrease experiment size and improve phenotype detection

The paper develops a statistical test to improve hit detection in CRISPR screens by accounting for asymmetric gRNA abundance changes, allowing smaller experiment sizes.

Systematic functional analysis of Rab GTPasesreveals limits of neuronal robustness in Drosophila

This study systematically analyzes Rab GTPase function in Drosophila neurons, revealing that some Rabs are critical for robustness to environmental challenges despite being viable in null mutants.

A large-scale resource for tissue-specific CRISPR mutagenesis in Drosophila

The paper introduces a large-scale CRISPR mutagenesis library in Drosophila for targeted gene disruption, showing high efficiency and revealing new developmentally essential genes.

Gene expression atlas of a developing tissue by single cell expression correlation analysis

The paper develops a new method for analyzing scRNA-seq data based on gene expression correlations to generate a gene expression atlas of the Drosophila wing disc, identifying 824 genes with spatially restricted expression patterns.

Lineage specific core-regulatory circuits determine gene essentiality in cancer cells

The paper identifies lineage-specific core-regulatory circuits in cancer cells and shows their role in gene essentiality and therapeutic vulnerability.

Time-resolved mapping of genetic interactions to model rewiring of signaling pathways

The paper identifies time-dependent genetic interactions in Drosophila cells using RNAi screens and develops an algorithm to analyze rewiring of signaling pathways.