- Skin and Cellular Biology Research
- Cancer Cells and Metastasis
- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Dermatological and Skeletal Disorders
- Wnt/β-catenin signaling in development and cancer
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- Ferroptosis and cancer prognosis
- 3D Printing in Biomedical Research
- Cancer Genomics and Diagnostics
- Cell Image Analysis Techniques
- Metabolomics and Mass Spectrometry Studies
- FOXO transcription factor regulation
- Birth, Development, and Health
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Molecular Biology Techniques and Applications
- Contact Dermatitis and Allergies
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Mast cells and histamine
- Congenital heart defects research
- Digestive system and related health
- RNA regulation and disease
Breast Cancer Now
2016-2023
Institute of Cancer Research
2017-2023
Institute of Cancer Research
2016
Queen Mary University of London
2011-2014
Abstract SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that mutant ( MUT ) cells selectively sensitive poly (ADP-ribose) polymerase inhibitors (PARPi), independent mutation site. display defective response PARPi-induced replication stress occurs via downregulation the cyclin-dependent kinase 2 interacting protein (CINP), leading increased fork origin...
Proteomic analysis of extracellular matrix (ECM) and ECM-associated proteins, collectively known as the matrisome, is a challenging task due to inherent complexity insolubility these proteins. Here we present sequential window acquisition all theoretical fragment ion spectra mass spectrometry (SWATH MS) tool for quantitative matrisomal proteins in both non-enriched ECM enriched tissue without need prior fractionation. Utilising spectral library containing 201 compared performance...
Abstract Here, we show that SOX11, an embryonic mammary marker is normally silent in postnatal breast cells, expressed many oestrogen receptor‐negative preinvasive ductal carcinoma situ (DCIS) lesions. Mature epithelial cells engineered to express SOX11 showed alterations progenitor cell populations, including expanded basal‐like population with increased aldehyde dehydrogenase (ALDH) activity, and mammosphere‐forming capacity. DCIS.com ALDH which a feature of cancer stem cells. The...
The identification of functional driver events in cancer is central to furthering our understanding biology and indispensable for the discovery next generation novel drug targets. It becoming apparent that more complex models are required fully appreciate contributing factors drive tumorigenesis vivo increase efficacy therapies make transition from pre-clinical clinical trials. Here we present a methodology generating uniform reproducible tumor spheroids can be subjected siRNA screening....
SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here, we present a comprehensive mouse reference spectral library (MouseRefSWATH) that permits quantification of up to 10,597 proteins (62.2% proteome) by SWATH-MS. We exploit MouseRefSWATH develop an analytical pipeline for species-specific deconvolution alterations human tumour xenografts (XenoSWATH). This method overcomes challenge high sequence similarity...
Embryonic mammary cells are a unique population comprised of undifferentiated, highly plastic progenitor that create normal tissues. The gland continues to develop after birth from descendants embryonic cells. Here, we establish cell lines mouse organs, immediately they formed during prenatal development, facilitate studies primitive cells, which difficult isolate in sufficient quantities for use functional experiments. We show some can be induced secrete milk, distinguishing feature...
Triple-negative breast cancers (TNBC) are resistant to standard-of-care chemotherapy and lack known targetable driver gene alterations. Identification of novel drivers could aid the discovery new treatment strategies for this hard-to-treat patient population, yet studies using high-throughput accurate models define functions genes in TNBC date have been limited. Here, we employed unbiased functional genomics screening 200 most frequently mutated cancer, spheroid cultures model
The identification of functional driver events in cancer is central to furthering our understanding biology and indispensable for the discovery next generation novel drug targets. It becoming apparent that more complex models are required fully appreciate contributing factors drive tumorigenesis vivo increase efficacy therapies make transition from pre-clinical clinical trials. Here we present a methodology generating uniform reproducible tumor spheroids can be subjected siRNA screening....
Abstract SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here we present a comprehensive mouse reference spectral library (MouseRefSWATH) that permits quantification of up to 10,597 proteins (62.2% proteome) by SWATH-MS. We exploit MouseRefSWATH develop an analytical pipeline for species-specific deconvolution alterations human tumour xenografts (XenoSWATH). This method overcomes challenge high sequence...
Abstract SF3B1 hotspot mutations are highly prevalent in several tumor types, where they lead to a global disruption of canonical splicing and associated with poor clinical outcome. Whilst evidence suggests that spliceosomal inhibitors have therapeutic benefit for specific mutant cancers, recent trials failed report any responses. Here we used myriad vitro vivo techniques identify explore synthetic lethal vulnerability cancers. These included high throughput drug screen an in-house curated...
Abstract Solid tumors display significant histological, genetic and micro-environmental intra-tumor heterogeneity that can change substantially over the course of their evolutionary trajectory. In particular, changes in complexity within breast cancer such as hypoxic nutrient deplete environments are associated with aggressive disease a poor patient outcome. We sought to identify novel driver alterations by employing functional genomics screen 3-dimensional model progression more accurately...