A5090637134- Tracheal and airway disorders
- Tissue Engineering and Regenerative Medicine
- Airway Management and Intubation Techniques
- Esophageal and GI Pathology
- Electrospun Nanofibers in Biomedical Applications
- Congenital Diaphragmatic Hernia Studies
- Dysphagia Assessment and Management
- Neonatal Respiratory Health Research
- Voice and Speech Disorders
- Teratomas and Epidermoid Cysts
- Trauma Management and Diagnosis
- Lung Cancer Treatments and Mutations
- SARS-CoV-2 and COVID-19 Research
- Nasal Surgery and Airway Studies
- Cystic Fibrosis Research Advances
- Neuroendocrine Tumor Research Advances
- Vascular Anomalies and Treatments
- Head and Neck Surgical Oncology
- Salivary Gland Tumors Diagnosis and Treatment
- COVID-19 Clinical Research Studies
- Wnt/β-catenin signaling in development and cancer
- Sarcoidosis and Beryllium Toxicity Research
- Cancer Cells and Metastasis
- Reconstructive Surgery and Microvascular Techniques
- Pituitary Gland Disorders and Treatments
University College London
2016-2025
Great Ormond Street Hospital
2016-2025
Great Ormond Street Hospital for Children NHS Foundation Trust
2014-2024
The Royal Free Hospital
2023
Roland Hill (United Kingdom)
2023
The University of Adelaide
2021
NIHR Great Ormond Street Hospital Biomedical Research Centre
2021
Ormond (United States)
2021
Cancer Institute (WIA)
2021
CRUK Lung Cancer Centre of Excellence
2021
It is not fully understood why COVID-19 typically milder in children
Rationale: Stem cell–based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital stenosis and upper tumors. Clinical experience demonstrates that restoration of mucociliary clearance in the lungs after transplantation tissue-engineered grafts is critical, preclinical studies showing seeding scaffolds autologous mucosa improves regeneration. High epithelial cell–seeding densities are required...
Abstract Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in people over 85 years age remains high. Here we investigate differences cellular landscape and function paediatric (<12 years), adult (30–50 years) older (>70 ex vivo cultured nasal epithelial cells response infection SARS-CoV-2. We show that cell tropism SARS-CoV-2, expression ACE2 TMPRSS2 subtypes, differ between groups. While ciliated are viral replication centres...
In 2010, a tissue-engineered trachea was transplanted into 10-year-old child using decellularized deceased donor repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report child's clinical progress, tracheal epithelialization costs over 4 years. A chronology of events derived from notes determined reference per procedure. Serial tracheoscopy images, lung function tests anti-HLA blood samples were compared. Epithelial morphology T cell, Ki67 cleaved...
Abstract Tracheal replacement for the treatment of end-stage airway disease remains an elusive goal. The use tissue-engineered tracheae in compassionate cases suggests that such approach is a viable option. Here, stem cell-seeded, decellularized tracheal graft was used on basis girl with critical stenosis after conventional reconstructive techniques failed. represents first cell-seeded manufactured to full good manufacturing practice (GMP) standards. We report important preclinical and...
Patients with large tracheal lesions unsuitable for conventional endoscopic or open operations may require a replacement but there is no present consensus of how this be achieved. Tissue engineering using decellularized synthetic scaffolds offers new avenue airway reconstruction. Decellularized human donor have been applied in compassionate-use clinical cases naturally derived extracellular matrix (ECM) demand lengthy preparation times. Here, we compare clinically detergent-enzymatic method...
Human lung cancers, including squamous cell carcinoma (SCC) are a leading cause of death and, whilst evidence suggests that basal stem cells drive SCC initiation and progression, the mechanisms regulating these processes remain unknown. In this study we show β-catenin signalling regulates progenitor fate subsequent progression. cohort preinvasive SCCs established elevated is positively associated with increased disease severity, epithelial proliferation reduced intercellular adhesiveness. We...
Polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) is a versatile nanocomposite biomaterial with growing applications as bioscaffold for tissue engineering. Integration of synthetic implants host can be problematic but could improved by topographical modifications. We describe optimization POSS-PCU dispersion porogens (sodium bicarbonate (NaHCO3), sodium chloride (NaCl) and sucrose) onto the material surface, principle aim increasing surface porosity, thus...
To audit the accuracy of otolaryngology clinical coding and identify ways improving it.Prospective multidisciplinary audit, using 'national standard audit' methodology supplemented by 'double-reading arbitration'.Teaching-hospital departments.Otolaryngology inpatient day-surgery cases.Concordance between initial performed a coder (first cycle) final clinician-coder team (MDT; second for primary secondary diagnoses procedures, Health Resource Groupings (HRG) assignment.1250 randomly-selected...
Despite surgical advances, childhood tracheal stenosis is associated with high morbidity and mortality. Various scaffold strategies have been developed as the basis for bioengineered substitutes, but there no consensus on which may be superior in vivo. We hypothesized that would difference mortality between three competing rabbits.Pilot preclinical study.Tracheal scaffolds were prepared by methods applied clinically reported: preserved cadaveric ("Herberhold") allografts,...
Current methods to replace damaged upper airway epithelium with exogenous cells are limited. Existing strategies use grafts that lack mucociliary function, leading infection and the retention of secretions keratin debris. Strategies regenerate function clearly desirable would enable new treatments for complex disease.Here, we investigated influence extracellular matrix (ECM) on epithelial cell adherence, proliferation in context bioengineered mucosal grafts. In vitro, primary human bronchial...
The airway epithelium is a protective barrier that maintained by the self-renewal and differentiation of basal stem cells. Increasing age principle risk factor for chronic lung diseases, but few studies have explored age-related molecular or functional changes in epithelium. We retrieved epithelial biopsies from histologically normal tracheobronchial sites pediatric adult donors compared their cellular composition gene expression profile (in laser capture-microdissected whole epithelium,...
The hallmark of epidermolysis bullosa (EB) is fragile attachment epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated the ear, nose, and throat department a tertiary pediatric hospital linked United Kingdom's national unit between 1992 2023. Patients suffered high degree morbidity mortality from laryngotracheal stenosis. Variants laminin subunit alpha-3 (LAMA3) were found 10/15 where genotype was available. LAMA3 encodes laminin-332 heterotrimeric...
Background Development of therapeutic approaches for rare respiratory diseases is hampered by the lack systems that allow medium-to-high-throughput screening fully differentiated epithelium from affected patients. This a particular problem primary ciliary dyskinesia (PCD), genetic disease caused mutations in genes adversely affect movement and consequently mucociliary transport. Primary cell culture basal epithelial cells nasal brush biopsies followed ciliated differentiation at air–liquid...
The primary cause of death in Morquio A syndrome (mucopolysaccharidosis (MPS) IVA) is airway obstruction, brought about by an inexorable and pathognomonic multilevel tortuosity, buckling, obstruction. relative pathophysiological contributions inherent cartilage processing defect versus a mismatch longitudinal growth between the trachea thoracic cage are currently subject debate. Enzyme replacement therapy (ERT) multidisciplinary management continue to improve life expectancy for patients...