Extracellular vesicles in the propagation of lung injury in critical care and perioperative patients

Our goal is to translate insights from EV biology into new strategies to predict, prevent, or treat organ complications in high-risk surgical and ICU populations.

Our research is working toward:

• New biomarkers: EVs carry unique molecular cargo (proteins, lipids, RNAs) that reflect disease state. Analysing EVs from bronchoalveolar lavage or blood may allow earlier, more precise detection of PPCs or AKI.
• Therapeutic targets: We are investigating how acid sphingomyelinase (ASM) drives pro-inflammatory EV release during mechanical ventilation, and whether blocking ASM (with functional inhibitors of ASM e.g. imipramine) can reduce lung injury.
• Risk stratification and personalisation: Understanding EV profiles may help tailor perioperative and ventilatory strategies to reduce the risk of PPCs and other complications.

Our ultimate goal is to reduce the incidence and severity of postoperative and ICU-related complications, leading to shorter hospital stays, fewer readmissions, and better long-term outcomes.

We are currently engaged in a range of basic science, translational, and patient-facing research projects, including:

1. EV-mediated lung inflammation and PPCs
   Investigating how mechanical stretch during ventilation triggers ASM activation and pro-inflammatory EV release from alveolar immune cells.
   Analysing EVs from patients undergoing oesophagectomy, who are at high risk of lung inflammation/injury due to one-lung ventilation.
2.  Acid sphingomyelinase (ASM) as a therapeutic target
   Exploring how ASM regulates EV production and cargo packaging, with pharmacological inhibition (e.g. imipramine) as a potential protective strategy.
   Studying ASM expression and EV profiles in perioperative BAL fluid samples, linked to real-time clinical outcomes.
3. Extracellular vesicles in AKI
   Identifying how neutrophil- and monocyte-derived EVs contribute to renal endothelial inflammation and damage in critically ill patients.
   Using novel imaging flow cytometry and lipidomic analysis to characterise renal-targeting EVs and their role in AKI pathogenesis.
4.  Ongoing collaborations and clinical data collection
   Embedding EV profiling in large-scale patient cohorts, including those undergoing major surgery and those with COVID-19-related ARDS.
   Working with infectious disease to assess the role of bacterial-derived EVs

• Academy of Medical Sciences (P86239)
• British Journal of Anaesthesia, National Institute of Academic Anaesthesia (P89938)
• Medical Research Council (P54008)

Internal 

Professor Fan Chung

External

• Professor Wolfgang Kuebler
• Professor Pallav Shah

Imperial College NHS Trust

Koh MW, Baldi RF, Soni S, Handslip R, Tan YY, O'Dea KP, Malesevic M, McAuley DF, O'Kane CM, Patel BV, Takata M, Wilson MR. Secreted Extracellular Cyclophilin A is a Novel Mediator of Ventilator Induced Lung Injury. Am J Respir Crit Care Med. 2021 Apr 13. doi: 10.1164/rccm.202009-3545OC.

Soni S, Garner J, O;dea K, Koh, M, Tirlapur N, Srikanthan K, Tenda R, Faelkady A, Singh S, Wilson MR, Kemp S, Usmani O, Shah P, Takata M. Intra-alveolar neutrophil-derived microvesicles are associated with disease severity in COPD. Am J Physiol Lung Cell Mol Physiol. 2021 Jan 1;320(1): L73-L83.

 Chia G, Barrett H, Patel P, Soni S. One hundred eighteen days on a ventilator: a COVID-19 success story against all odds. BMJ Case Rep. 2021 Mar 29;14(3):e239631.

Chaggar RS, Shah SV, Berry M, Saini R, Soni S, Vaughan D. The Video Classification of Intubation (VCI) score: a new description tool for tracheal intubation using videolaryngoscopy: A pilot study. Eur J Anaesthesiol. 2021 Mar 1;38(3):324-326.

Stephens JR, Wong JLC, Broomhead R, Stümpfle R, Waheed U, Patel P, Brett SJ, Soni S. Raised serum amylase in patients with COVID-19 may not be associated with pancreatitis. Br J Surg. 2021 Apr 30;108(4):e152-e153.

Gasparini M, Khan S, Patel J, Parekh D, Bangash M, Stumpfle R, Shah A, Baharlo B and Soni S. Renal impairment and its impact on clinical outcomes in critically ill patients with COVID-19: a UK multicentre observational study. Anaesthesia 2021.

Stephens J, Stumpfle R, Patel P, Brett S, Broomhead R, Baharlo B and Soni S. Analysis of critical care severity of illness scoring systems in patients with COVID-19: a retrospective analysis of three UK intensive care units. Crit Care Med 2021.

Soni S, Shah S, Chaggar R, Saini R, James E, Elliot J, Stephens J, McCormack T, Hartle A. Surgical cancellation rates due to peri-operative hypertension: Implementation of multi-disciplinary guidelines across primary and secondary care. Anaesthesia 2020;75(10):1314-1320

O'Dea KP, Tan YY, Shah S, V Patel B, C Tatham K, Wilson MR, Soni S, Takata M. Monocytes mediate homing of circulating microvesicles to the pulmonary vasculature during low grade systemic inflammation. Journal of extracellular vesicles. 2020; 5;9(1):1706708 2nd senior author

Soni S, Tirlapur N, O'Dea KP, Takata M, Wilson MR. Microvesicles as new therapeutic targets for the treatment of the acute respiratory distress syndrome (ARDS). Expert Opin Ther Targets. 2019;23(11):931-941

Oakley C, Koh M, Baldi R, Soni S, O'Dea K, Takata M, Wilson M. Ventilation following established ARDS: a preclinical model framework to improve predictive power. Thorax. 2019;74(12):1120-1129.

Soni S, O'Dea KP, Tan YY, Cho K, Abe E, Romano R, Cui J, Ma D, Sarathchandra P, Wilson MR, Takata M. Danger signals redirect cytokine trafficking and promote novel membrane TNF signalling via microvesicles. FASEB J. 2019:fj201802386R.

Soni S, Wilson MR, O'Dea KP, Yoshida M, Katbeh U, Woods SJ, Takata M. Alveolar macrophage-derived microvesicles mediate acute lung injury. Thorax. 2016 Nov;71(11):1020-1029.