A5024725594- PI3K/AKT/mTOR signaling in cancer
- Chromatin Remodeling and Cancer
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Genetic factors in colorectal cancer
- Cancer Research and Treatments
- Inflammatory Bowel Disease
- Cancer Mechanisms and Therapy
- Digestive system and related health
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
University of Cambridge
2024-2025
Lymphatic Education & Research Network
2023-2025
Cancer Research UK Cambridge Center
2024
Loss-of-function mutations in the tumour suppressor APC are an initial step intestinal tumorigenesis
Organoids, combined with genetic editing strategies, have the potential to offer rapid and efficient investigation of gene function in many models human disease. However, date, efficiency organoids use non-viral electroporation methods has only been up 30%, implications for subsequent need selection, including turnaround time exhaustion or adaptation organoid population. Here, we describe an method intestinal using a ribonucleoprotein-based CRISPR approach. Editing efficiencies 98% target...
Cancer driver mutations are defined by their high prevalence in cancers and presumed rarity normal tissues. However, recent studies show that positive selection epithelia can increase the of some cancer drivers. To determine true cancer-driving potential, it is essential to evaluate how frequent these tissues what phenotypes. Here, we explore bioavailability somatic variants quantifying age-related mutational burdens human colonic epithelium using immunodetection FFPE samples (N = 181...
In the progression from Inflammatory Bowel Disease to associated cancer, clonal mutational landscape shifts selection of mutations in inflammatory genes cancer-driver mutations1-4. How prevalence and expansion either type mutated clones could be impacted by cellular environment which they arise, how this affects neoplastic outcome colitis is unknown. Here, we combine vivo lineage tracing, in-silico modelling, profiling spatial transcriptomics a mouse model colitis-associated tumorigenesis...
Abstract Normal aged tissues are thought to exist as a patchwork of mutant clones. However, the relevance driver mutations in normal tissue terms cancer initiation has not been well described. Here, we sought quantitative understanding how different drivers achieve an age-related mutational footprint human colonic epithelium and relate clonal behaviours they generate risk. Metanalysis contemporary multiregional sampling studies colorectal tumours revealed many weak or moderate trunk present...
Mutant clones increasingly occupy normal human tissues with age but have unknown implications for subsequent cancer risk. In part, this is because the presence of such inferred and not directly observed in situ preventing identification conferred cellular properties likely to impact Here, an immuno-screen colorectal driver events identified PTEN, SMAD4 ARID1A deficient colon FFPE surgical resection samples (N=182 patients). Age-related changes clone size frequency positive biases dynamics...
Abstract Organoids are currently one of the most widely used ex vivo models in epithelial biology. Combined with genetic editing strategies, organoids offer a promise rapid and efficient investigation gene function many human disease. However, to date, efficiency use non-viral electroporation methods has been only up 30%, implications for subsequent need selection including turnaround time exhaustion or adaptation organoid population. Here, we describe an method intestinal using...