A5067420727- 3D Printing in Biomedical Research
- Cardiac Imaging and Diagnostics
- Cancer Cells and Metastasis
- Advanced MRI Techniques and Applications
- Spectroscopy Techniques in Biomedical and Chemical Research
- Nanoplatforms for cancer theranostics
- Cancer, Hypoxia, and Metabolism
- Ultrasound and Hyperthermia Applications
- RNA Interference and Gene Delivery
- Nanoparticle-Based Drug Delivery
- Tissue Engineering and Regenerative Medicine
- Cardiomyopathy and Myosin Studies
- Hepatocellular Carcinoma Treatment and Prognosis
- Renal cell carcinoma treatment
- Congenital heart defects research
- Photodynamic Therapy Research Studies
- Genomics and Rare Diseases
- Radiomics and Machine Learning in Medical Imaging
- Pancreatic and Hepatic Oncology Research
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Medical Imaging Techniques and Applications
- Photoacoustic and Ultrasonic Imaging
- Lung Cancer Treatments and Mutations
- Cell Image Analysis Techniques
Institute of Cancer Research
2021-2023
The Francis Crick Institute
2019-2022
University College London
2014-2022
Breast Cancer Now
2022
Transnational Press London
2020
CAB International
2019
The Honourable Society of Lincoln's Inn
2013-2015
Medical Research Council
2014
British Heart Foundation
2014
Royal Brompton & Harefield NHS Foundation Trust
2014
Highlights•ACSS2 expression positively correlates with tumor stage and patient survival•Hypoxia low lipid availability synergistically stimulate ACSS2 expression•Acetate is a major source of carbon for synthesis during metabolic stress•ACSS2 required growth xenografts harboring copy-number gainsSummaryA functional genomics study revealed that the activity acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell under low-oxygen lipid-depleted conditions. Comparative metabolomics lipidomics...
Mutant Pik3ca gives rise to venous malformations.
Highlights•Inducible disruption of PI3-kinase p110α interaction with RAS was modeled in mice•Blocking RAS/p110α established lung tumors causes partial regression•Blocking binding has effects similar to deletion on tumor regression•Coordinate MEK inhibition is required for major regression Kras mutant cancerSummaryRAS proteins directly activate PI3-kinases. Mice bearing a germline mutation the domain subunit PI3-kinse are resistant development RAS-driven tumors. However, it unknown whether...
The magnetic properties and safety of dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) have facilitated their clinical use as MRI contrast agents stimulated research on applications for SPIONs in particle imaging hyperthermia. wider potential SPIONs, however, has been limited by rapid removal from circulation via the reticuloendothelial system (RES). We explored possibility extending SPION circulatory time using fucoidan, a seaweed-derived food supplement, to inhibit RES...
Deubiquitylating enzymes (DUBs) play an essential role in targeted protein degradation and represent emerging therapeutic paradigm cancer. However, their potential pancreatic ductal adenocarcinoma (PDAC) has not been explored. Here, we develop a DUB discovery pipeline, combining activity-based proteomics with loss-of-function genetic screen patient-derived PDAC organoids murine models. This approach identifies USP25 as master regulator of growth maintenance. Genetic pharmacological...
Abstract Magnetic hyperthermia (MH) harnesses the heat‐releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility localized MH vivo, SPIONs are injected intratumorally their fate tracked by Zirconium‐89‐positron emission tomography, histological analysis, electron microscopy. Experiments show that an average 49% (21–87%, n = 9) retained...
Abstract Background MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though therapies are typically designed with target tissue in mind, delivery rarely assessed due lack translatable non-invasive imaging approaches. In this preclinical study, we demonstrate 89 Zr-oxine labelling and PET-CT as potential clinical solution for non-invasively tracking biodistribution. Future implementation...
Diffuse interstitial fibrosis is present in diverse cardiomyopathies and associated with poor prognosis. We investigated whether magnetic resonance imaging-based T1 mapping could quantify the induction pharmacological suppression of diffuse cardiac murine pressure-overload hypertrophy.Mice were subjected to transverse aortic constriction or sham surgery. The angiotensin receptor blocker losartan was given half animals. Cine-magnetic imaging performed at 7 28 days showed hypertrophy...
Alginate hydrogels are cross-linked polymers with high water content, tuneable chemical and material properties, a range of biomedical applications including drug delivery, tissue engineering, cell therapy. However, their similarity to soft often renders them undetectable within the body using conventional bio-medical imaging techniques. This leaves much unknown about behaviour in vivo, posing challenge therapy development validation. To address this, we report novel, fast, simple method...
Significance: Tumor detection and margin delineation are essential for successful tumor resection. However, postsurgical positive rates remain high many cancers. Raman spectroscopy has shown promise as a highly accurate clinical spectroscopic diagnostic modality, but its capabilities severely limited by the need pointwise application. Aim: We aim to extend diagnostics develop multimodal computer vision-based system capable of both identification suspicious lesions precise disease margins....
Targeted drug delivery systems aim to increase therapeutic effect within the target tissue or organ, while reducing off-target toxicity associated with systemic delivery. Magnetic targeting has been shown be an effective strategy by manipulating therapeutics inside body using a magnetic field and iron oxide carrier. However, range of current magnets limits this method small animal experiments superficial parts human body. Here we produce clinically translatable magnet designs capable...
Mineralisation of radio-metals onto the surface iron oxide nanoparticles simplifies radiolabelling, enabling quantification their bio-distribution with nuclear imaging.
Illustration of adipose-derived stem cells with tri-modal imaging capabilities for evaluating the efficiency cell delivery to tumours.
Abstract Cell-based therapies are promising treatments for various kidney diseases. However, the major hurdle in initiating therapeutic responses is inefficiency of injection routes to deliver cells parenchyma. Systemic injection, such as intravenous only delivers a small proportion kidney. Whereas direct delivery, renal artery requires surgical procedures. A minimally invasive was therefore developed enhance cell delivery In this study, luciferase expressing human adipocyte derived stem...
Theranostics, the combination of diagnosis and therapy, has long held promise as a means to achieving personalised precision cancer treatments.However, despite its potential, theranostics yet realise significant clinical translation, largely due complexity overriding toxicity concerns existing theranostic nanoparticle strategies.Methods: Here, we present an alternative nanoparticle-free approach based on simultaneous Raman spectroscopy photodynamic therapy (PDT) in integrated platform for...
Early measurements of tissue viability after myocardial infarction (MI) are essential for accurate diagnosis and treatment planning but challenging to obtain. Here, manganese, a calcium analogue clinically approved magnetic resonance imaging (MRI) contrast agent, is used as an biomarker in the first hours experimental MI. Safe Mn
Abstract Optical imaging in clinical and preclinical settings can provide a wealth of biological information, particularly when coupled with targetted nanoparticles, but optical scattering absorption limit the depth resolution both animal human subjects. Two new hybrid approaches are presented, using penetrating power X-rays to increase imaging. Foremost, we demonstrate excitation by quantum-dots (QD) emitting near-infrared (NIR), X-ray system map distribution QDs at whole mouse. We elicit...
The design, synthesis and formulation of non‐viral gene delivery vectors is an area renewed research interest. Amongst the most efficient systems are lipopolyplexes, in which cationic peptides co‐formulated with plasmid DNA lipids. One advantage lipopolyplex that they have potential to be targeted specific cell types by attaching peptide targeting ligands on surface, thus increasing both transfection efficiency selectivity for disease targets such as cancer cells. In this paper, we...
The protein kinase PKN2 is required for embryonic development and knockout mice die as a result of failure in the expansion mesoderm, cardiac neural tube closure. In adult, cardiomyocyte PKN1 (in combination) are adaptation to pressure-overload. specific role contractile cardiomyocytes during its adult heart remain be fully established. We used with cardiomyocyte-directed or global haploinsufficiency assess function using high resolution episcopic microscopy, MRI, micro-CT echocardiography....
Abstract Ras proteins are one of the most prevalent oncogenic drivers human cancer and lung, pancreatic colon cancers frequently harbor mutated forms KRAS gene. The role is executed via direct interaction with, activation of, a number downstream effectors including PI 3-kinases, Raf kinases, RalGDS Tiam1. Previously our laboratory has demonstrated that disruption 3-kinase by K-Ras, mutation two key residues (T208D K227A) in binding domain p110alpha ( p110alpha-RBD), prevents tumor...