My primary research interest is the propagation of lung injury in critically unwell patients. To date, this has predominantly focused upon the role of microvesicles in acute respiratory distress syndrome. I am primarily interested in cellular communication and the transfer of inflammatory cargo/milieu between alveolar and pulmonary cells. We are also currently exploring the role of microvesicles in COVID-19 induced ARDS and multi-organ failure.
Most recently, we have demonstrated a dynamic production of microvesicles from multiple intra-alveolar cells early in the inflammatory course of acute lung injury (ALI) particularly from alveolar macrophages. When instilled into murine lungs, these microvesicles induced lung injury via a TNF dependent mechanism. We found that TNF is released within microvesicles via an unconventional endoplasmic reticulum/Golgi-independent route (similar to IL-1β), despite being a classical, golgi-dependant cytokine. Interestingly, we demonstrated that this switch in cellular TNF trafficking is mediated via acid sphingomyelinase.
We also characterised microvesicle populations within bronchoalveolar lavage taken from COPD patients and found that neutrophil-derived microvesicles strongly correlated with disease severity. We have similarly characterised microvesicles populations in bronchoalveolar lavage fluid taken from patients post lung tranplantation with Primary Graft Dysfunction (PGD) and in patients with Acute Respiratory Distress Syndrome (ARDS).
I have presented our work to the worldwide scientific and intensive care communities. I have been awarded a number of international and national prizes including European Respiratory Society Young Investigator Abstract Grant in Lung Transplantation (2020), the British Association of Lung Research Early Career Investigator Award (2019), the American Thoracic Society International Trainee Scholarship Award (2014 and 2018), Original Research prize at an NIHR Clinical Research event (2018) and Royal Society of Medicine: Anaesthesia Section Prize (2018).
My PhD was jointly funded as a Clinical Research Training Fellowship by the Medical Research Council and the British Journal of Anaesthesia. Our current work is funded by the Academy of Medical Sciences and Chelsea and Westminster Health Charity. We are collaborating with Professor Wolfgang Kübler (Charite University, Berlin) and this work has been funded by a European Respiratory Society Research Training Fellowship.
My clinical time is spent at Imperial College NHS Trust (Hammersmith Hospital) within the departments of Intensive Care Medicine and Anaesthesia.
et al., 2022, Clinical and Survival differences during separate COVID-19 surges: investigating the impact of the Sars-CoV-2 alpha variant in critical care patients, Plos One, Vol:17, ISSN:1932-6203
et al., 2022, Recommended reading from the Imperial College, London fellows, American Journal of Respiratory and Critical Care Medicine, Vol:205, ISSN:1073-449X, Pages:1470-1473
et al., 2022, Microvesicle-mediated communication within the alveolar space: mechanisms of uptake by epithelial cells and alveolar macrophages, Frontiers in Immunology, Vol:13, ISSN:1664-3224
et al., 2022, Patient outcomes following transfer between intensive care units during the COVID-19 pandemic, Anaesthesia, Vol:77, ISSN:0003-2409, Pages:398-404
et al., 2021, Secreted extracellular cyclophilin a is a novel mediator of ventilator induced lung injury., American Journal of Respiratory and Critical Care Medicine, Vol:204, ISSN:1073-449X, Pages:421-430