A5011633404- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Nanowire Synthesis and Applications
- Hippo pathway signaling and YAP/TAZ
- Silicon Carbide Semiconductor Technologies
- Innovative Microfluidic and Catalytic Techniques Innovation
- 3D Printing in Biomedical Research
- Viral Infectious Diseases and Gene Expression in Insects
- Estrogen and related hormone effects
- PI3K/AKT/mTOR signaling in cancer
- Genetic factors in colorectal cancer
- Wnt/β-catenin signaling in development and cancer
- Immune Cell Function and Interaction
- Clusterin in disease pathology
- Cancer Mechanisms and Therapy
- Asthma and respiratory diseases
- Cancer, Stress, Anesthesia, and Immune Response
- CRISPR and Genetic Engineering
- Extracellular vesicles in disease
- RNA modifications and cancer
- RNA Research and Splicing
- Molecular Biology Techniques and Applications
- Immune cells in cancer
London Cancer
2019-2024
University College London
2019-2024
Cancer Institute (WIA)
2019-2020
Imperial College London
2015
Cancer cells are regulated by oncogenic mutations and microenvironmental signals, yet these processes often studied separately. To functionally map how cell-intrinsic cell-extrinsic cues co-regulate cell fate, we performed a systematic single-cell analysis of 1,107 colonic organoid cultures (1) colorectal cancer (CRC) mutations, (2) fibroblasts macrophages, (3) stromal ligands, (4) signaling inhibitors. Multiplexed revealed stepwise epithelial differentiation phenoscape dictated combinations...
Abstract We recently described a low-affinity second-generation CD19 chimeric antigen receptor (CAR) CAT that showed enhanced expansion, cytotoxicity, and antitumor efficacy compared with the high-affinity (FMC63-based) CAR used in tisagenlecleucel, preclinical models. Furthermore, demonstrated an excellent toxicity profile, vivo long-term persistence phase 1 clinical study. To understand molecular mechanisms behind these properties of T cells, we performed systematic vitro characterization...
We present SIGNAL-seq (Split-pool Indexing siG-Nalling AnaLysis by sequencing): a multiplexed splitpool combinatorial barcoding method that simultaneously measures RNA and post-translational modifications (PTMs) in fixed single cells from 3D models. PTM measurements are equivalent to mass cytometry gene detection is analogous split-pool scRNA-seq. By measuring both mRNA ligand-receptor pairs PTMs cells, can uncover inter- intra-cellular regulation of tumour microenvironment plasticity.
Cancer cells are regulated by oncogenic mutations and microenvironmental signals, yet these processes often studied separately. To functionally map how cell-intrinsic cell-extrinsic cues co-regulate cell-fate in colorectal cancer (CRC), we performed a systematic single-cell analysis of 1,071 colonic organoid cultures 1) CRC mutations, 2) fibroblasts macrophages, 3) stromal ligands, 4) signalling inhibitors. Multiplexed revealed stepwise epithelial differentiation landscape dictated...
Here, we present a comprehensive protocol for the generation and functional characterization of chimeric antigen receptor (CAR) T cells their products by mass cytometry in reproducible scalable manner. We describe production CAR from human peripheral blood mononuclear cells. then detail three-step staining with metal-labeled antibodies subsequent analysis. This allows simultaneous cell intracellular signaling, activation, proliferation, cytokine production, phenotype single assay.
Abstract Patient-derived organoids (PDOs) can model personalized therapy responses, however current screening technologies cannot reveal drug response mechanisms or study how tumor microenvironment cells alter therapeutic performance. To address this, we developed a highly-multiplexed mass cytometry platform to measure post translational modification (PTM) signaling in >2,500 colorectal cancer (CRC) PDOs and cancer-associated fibroblasts (CAFs) clinical therapies at single-cell...
Organoids are powerful biomimetic tissue models. Despite their widespread adoption, methods to analyse cell-type specific post-translational modification (PTM) signalling networks in organoids absent. Here we report multivariate single-cell analysis of and organoid co-cultures. Simultaneous measurement 28 PTMs >1 million single small intestinal cells by mass cytometry reveals cell-state stem, Paneth, enteroendocrine, tuft, goblet cells, enterocytes. Integrating PTM with Thiol-reactive...
Abstract Pathological activation of the PI3K/AKT pathway is among most frequent defects in human cancer and also cause rare overgrowth disorders. Yet, there currently no systematic understanding quantitative flow information within signaling how it perturbed by disease-causing mutations. Here, we develop scalable, single-cell approaches for analyses signal processing PI3K pathway, enabling precise calculations its transfer different growth factors. Using genetically-engineered cell models...
Abstract Technical limitations have prevented understanding of how growth factor signals are encoded in distinct activity patterns the phosphoinositide 3-kinase (PI3K)/AKT pathway, and this is altered by oncogenic pathway mutations. We introduce a kinetic, single-cell framework for precise calculations PI3K-specific information transfer different factors. This features live-cell imaging PI3K/AKT reporters multiplexed CyTOF measurements RAS/ERK signaling markers over time. Using framework, we...
Abstract Colorectal cancer (CRC) is a devastating disease that kills ~700,000 people worldwide annually. Current immunotherapies struggle against both microsatellite stable (MSS) and the immunosuppressive CRC tumor microenvironment (TME). Despite these challenges, infiltrating γδ T cells confer prognostic benefit to patients can kill via antibody independent cytotoxicity (AIC) antibody-dependent cellular (ADCC). We hypothesized be exploited as an ‘off-the-shelf’ anti-CRC biotherapeutic but...
Abstract Patient-derived human organoids have the remarkable capacity to self-organise into more complex structures. However, what extent gastric can recapitulate stomach physiological functions remain unexplored. Here, we report how region-specific self-assemble multi-regional assembloids showing functional response drugs targeting ATPase H+/K+ pump. The show preserved fundus, body, and antrum regional identity, gastric-specific crosstalk pathways arise. increased complexity...
Abstract We recently described a low-affinity second-generation CD19 chimeric antigen receptor (CAR) CAT that showed enhanced expansion, cytotoxicity, and anti-tumour efficacy compared to the high-affinity (FMC63 based) CAR used in Tisagenlecleucel, pre-clinical models. Furthermore, demonstrated an excellent toxicity profile, vivo long-term persistence Phase I clinical study. To understand molecular mechanisms behind these properties of T-cells, we performed systematic vitro characterization...
<h3>Introduction</h3> Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy, accounting for approximately 15% of cases liver cancer. Although new treatments have increased survival many other cancers, including more hepatocellular carcinoma, treatment strategies and patients with ICC seen little improvement. Our previous studies suggest that mitogen-activated protein kinase (MAPK) signalling plays a central role in regulation cell proliferation human ICC....