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., 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
et al., 2021, Raised serum amylase in patients with COVID-19 may not be associated with pancreatitis, British Journal of Surgery, Vol:108, ISSN:0007-1323, Pages:152-153
et al., 2021, One hundred eighteen days on a ventilator: a COVID-19 success story against all odds, Bmj Case Reports, Vol:14, ISSN:1757-790X, Pages:1-4
et al., 2021, The Video Classification of Intubation (VCI) score: a new description tool for tracheal intubation using videolaryngoscopy, European Journal of Anaesthesiology, Vol:38, ISSN:0265-0215, Pages:324-326
et al., 2021, Intra-alveolar neutrophil-derived microvesicles are associated with disease severity in COPD, American Journal of Physiology: Lung Cellular and Molecular Physiology, Vol:320, ISSN:1040-0605, Pages:L73-L83