A5090776417- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Hippo pathway signaling and YAP/TAZ
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Histone Deacetylase Inhibitors Research
- Genomics and Chromatin Dynamics
- Wnt/β-catenin signaling in development and cancer
- PI3K/AKT/mTOR signaling in cancer
- Ubiquitin and proteasome pathways
Dana-Farber Cancer Institute
2022-2024
Harvard University
2022-2024
Broad Institute
2022-2024
Massachusetts Institute of Technology
2022-2024
Cell state plasticity is carefully regulated in adult epithelia to prevent cancer. The aberrant expansion of the normally restricted capability for cell neoplasia poorly defined. Using genetically engineered and carcinogen-induced mouse models intestinal neoplasia, we observed that impaired differentiation a conserved event preceding cancer development. Single-cell RNA sequencing (scRNA-seq) premalignant lesions from patient with hereditary polyposis revealed initiates by adopting an...
Objective Genomic studies of gastric cancer have identified highly recurrent genomic alterations impacting RHO signalling, especially in the diffuse (DGC) histological subtype. Among these are interchromosomal translations leading to fusion adhesion protein CLDN18 and regulator ARHGAP26. It remains unclear how constructs impact activity pathway what is their broader on development. Herein, we developed a model allow us study function this pathogenesis DGC identify potential therapeutic...
Dysregulated Wnt/β-catenin signaling is implicated in the pathogenesis of many human cancers, including colorectal cancer (CRC), making it an attractive clinical target. With aim inhibiting oncogenic Wnt activity, we developed a high-throughput screening AlphaScreen assay to identify selective small-molecule inhibitors interaction between β-catenin and its coactivator BCL9. We identified compound that consistently bound specifically inhibited vivo native β-catenin/BCL9 complex formation CRC...
ABSTRACT Dysregulated epigenetic programs that restrict differentiation, reactivate fetal genes, and confer phenotypic plasticity are critical to colorectal cancer (CRC) development. By screening a small molecule library targeting regulators using our dual reporter system, we found inhibiting histone deacetylase (HDAC) 1/2 promotes CRC differentiation anti-tumor activity. Comprehensive biochemical, chemical, genetic experiments revealed on-target blockade of the HDAC1/2 catalytic domain...
ABSTRACT Cell state (phenotypic) plasticity is a carefully regulated feature of adult epithelial cells that enables adaptive responses to injury, inflammation, and other forms stress. Aberrant expansion the normally restricted capability for cell escape terminal differentiation critical aspect neoplasia. The nongenetic factors specific programs mediate aberrant impaired require deeper characterization understand this elusive cancer pathogenesis. Using genetically engineered...
Abstract Despite the implementation of screening and preventative strategies, colorectal cancer (CRC) remains second most deadly worldwide is responsible for an alarming trend increasing prevalence among younger patients. Inappropriate WNT activation initiating step in sporadic CRC development, typically through deleterious mutations pathway negative regulator Adenomatous polyposis coli (APC). hinders whereas transforming growth factor (TGF-β)/bone morphogenetic protein (BMP) signaling...
Abstract Cell state plasticity – the ability of cells to acquire new states via differentiation programs - is an important feature embryogenesis, allowing for tissue specification during development, and adult homeostasis, enabling adaptive responses physiological cues pathological states. Epigenetic governance gene regulation endow epithelia with restricted cell that enable homeostasis while avoiding properties may facilitate neoplasia. There emerging evidence aberrant expansion normally...