Interstitial and Inflammatory Lung Disease

Principal Investigators

Interstitial lung diseases

The Interstitial lung diseases (ILDs) encompass a diverse group of disorders that damage the lung parenchyma, often driven by chronic inflammation and fibrosis, with the most common of these conditions including idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis and sarcoidosis. ILD is also associated with rheumatological conditions, including rheumatoid arthritis or scleroderma. Our research programmes focus on:

• defining molecular mechanisms (Chambers)
• computer-based CT analysis for disease stratification (Jacob)
• biomarker discovery and early-phase clinical trials for targeted therapies (Porter)
• advanced molecular imaging techniques (Groves)

They are supported by grants obtained from major funding agencies, including the Medical Research Council (UKRI/MRC), The Wellcome Trust, The Chan Zuckerberg Initiative (CZI) Asthma + Lung UK, The Rosetrees Trust and through collaborative funding obtained from industry partners.

Molecular mechanisms underlying the pathogenesis of ILD 

Our fundamental research programme, led by Professor Rachel Chambers, focusses on defining the signalling pathways, transcriptional responses and metabolic networks underlying the development of the maladaptive tissue injury response to acute and chronic lung injury. Our research approach integrates fundamental studies in patient-derived cells, advanced disease model systems, including ex-vivo precision-cut lung slices and lung organoids, through to early translational studies in humans. Recent work identified a critical role for the mTORC1 signalling node and metabolic reprogramming in pathological fibrogenesis with important implications for the development of future therapeutic strategies for IPF and other fibrotic conditions.

Biomarker and early-phase clinical trials for targeted therapies 

Led by Professor Joanna Porter, this programme focuses on biomarker discovery and early-phase clinical trials to advance targeted therapies for interstitial lung disease (ILD). Key research areas include leukocyte trafficking, inflammation, and the impact of aberrant glycosylation on immune regulation. Our preclinical work aims to refine patient stratification and enable precision medicine. 

Professor Porter also directs a regional NHS ILD specialty centre at University College London Hospitals and chairs the NIHR National Strategy Group for early-phase ILD research. 

We integrate molecular data, histology, molecular and cross-sectional imaging (with Professor Ashley Groves and Dr Joe Jacobs), and remote monitoring (with Prof. Hurst) to enhance disease profiling, patient stratification, and therapeutic targeting.

Computer-based CT analysis for disease stratification  

The Satsuma Lab led by Dr Joe Jacob develops advanced computer-based image analysis techniques to quantify lung fibrosis in its earliest stages (termed interstitial lung abnormalities) to its most advanced stages as seen in diseases such as IPF. The Satsuma lab applies image analysis tools to quantify early fibrosis in lung cancer screening populations such as the UCL SUMMIT study, substantiated by imaging of ex-vivo lungs at 3D microscopic scale resolution (HiP-CT) and allied to modern AI image analysis techniques.

Selected publications

1. Contento G, Wilson JA, Selvarajah B ... Chambers RC (2024). Pyruvate metabolism dictates fibroblast sensitivity to GLS1 inhibition during fibrogenesis. JCI Insight. 9(18):e178453.
2. Mehta P, Sanz-Magallón Duque de Estrada B ... Chambers RC, Porter JC, et al (2024). Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease. Front Immunol. 2024 May 17;15: 1372658.
3. Pakzad A ... Jacob J (2024). Evaluation of automated airway morphological quantification for assessing fibrosing lung disease. Computer Methods in Biomechanics and Biomedical Engineering: Imaging & Visualization.
4. Porter JC, Inshaw J, Solis VJ, et al (2024). Anti-inflammatory therapy with nebulized dornase alfa for severe COVID-19 pneumonia: a randomized unblinded trial. ELife: 12: 12:RP87030.
5. Althobiani MA, Ranjan Y, Russell A-M, Jacob J ... Porter JC, Folarin AA (2024). Home monitoring to detect progression of interstitial lung disease: A prospective cohort study.
6. Porter JC, Ganeshan B, Win T ... Groves AM (2024). [18F]FDG PET/CT Signal Correlates with Neo-angiogenesis Markers in Patients with Fibrotic Interstitial Lung Disease Who Underwent Lung Biopsy: Implication for the Use of PET/CT in Diffuse Lung Diseases. Journal of Nuclear Medicine 65 (3).
7. Stewart I, Jacob J ... Porter JC ... Chambers RC, et al (2023). Residual lung abnormalities following COVID-19 hospitalization: interim analysis of the UKILD Post-COVID study. Am J Respir Crit Care. Med. 207:693-703.
8. Cheung WC ... Hurst JR, Jacob J (2023). Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis. European Radiology. 33:8228-8238.
9. Bintalib HM, Van De Ven A AJM, Jacob J, et al (2023). Diagnostic testing for Interstitial Lung Disease in Common Variable Immunodeficiency: A Systematic Review. Frontiers in Immunology. 14:1190235.
10. Zhao A ... Jacob J (2023). Mortality surrogates in combined pulmonary fibrosis and emphysema European Respiratory Journal. 16:2300127.
11. Chong DLW, Mikolasch TA, Sahota J, Scotton CJ and Porter JC (2023). Investigating the role of platelets and platelet-derived transforming growth factor-β in idiopathic pulmonary fibrosis1 American Journal of Physiology: Lung Cellular and Molecular Physiology.
12. Mikolasch TA, George PM, Sahota J … Porter JC (2023). Multi-center evaluation of baseline neutrophil-to-lymphocyte (NLR) ratio as an independent predictor of mortality and clinical risk stratifier in idiopathic pulmonary fibrosis. EClinicalMedicine 55 Elsevier BV. 
13. Gudmundsson E ... Jacob J (2022). Delineating associations of progressive pleuroparenchymal fibroelastosis in patients with pulmonary fibrosis ERJ Open Res. 9:00637-2022.
14. Guillotin D, Taylor AR, Platé M ... Chambers RC. Transcriptome analysis of IPF fibroblastic foci identifies key pathways involved in fibrogenesis. Thorax 76:73-82, 2021.
15. Woodcock HV, Eley JD, Guillotin D … Chambers RC (2019). The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis. Nature Commun 10:6.

Funding and Grants

Prof. R Chambers
Medical Research Council (MRC) Consortium Award (2015-2025). Experimental Medicine Initiative to Explore New Therapies. MRC/GSK.
Award: £16,000,000.

Prof. J Porter
LifeArc Award (2020-2023): "A single-site, randomised, controlled, parallel design, open-label investigation of an approved nebulised recombinant human DNase enzyme (dornase alpha) to reduce hyperinflammation in hospitalised participants with COVID-19 (The COVASE trial)."
Award: £547,466.

Prof. R Chambers
Chiesi Farmaceutici SpA. Chiesi-UCL Fibrosis Research Collaboration (2021-2025).
Award: £1,162,029.

Prof. R Chambers, Dr J Jacob, Prof. JC Porter
Medical Research Council (MRC) Award (2021-2024). The UK Interstitial Lung Disease Long-COVID19 study (UKILD-Long COVID): understanding the burden of Interstitial Lung Disease in Long COVID.
Award: £530,518.

Prof. JC Porter
Boehringer Ingelheim International GmbH Award (2025-2027). The regulation and environmental impact of MUC1 carrying sialylated core 1 O-linked glycans in idiopathic pulmonary fibrosis; its targeting and biomarker potential.

Prof. JC Porter, Prof. R. Chambers
Medical Research Council (MRC) EMINENT Award (2024-2026). Do autoantibodies to aberrantly glycosylated MUC1 drive extra-articular rheumatoid arthritis, and can GSK assets prevent driver antigen formation?
Award: £314,369. 

Dr J Jacob
Wellcome Career Development Fellowship (2024-2032). Enhancing the characterisation of early respiratory disease to improve population health.
Award: £2,860,000.

Dr J Jacob
Chan Zuckerberg Institute (2024-2027). Developing a three-dimensional computed tomography foundational model to transform diagnosis of early disease in lung cancer screening populations.
Award: $3,800,000. 

Dr J Jacob
Rosetrees Trust (2024-2027). Quantifying the functional effects of vascular and airway changes in lung fibrosis and cystic fibrosis to evaluate disease progression and treatment response.
Award: £210,000.

Facilities and Techniques

• Post COVID ILD – a multicentre UK consortium investigating post COVID lung disease and providing a platform for other clinical studies including the single cell analysis of cells from bronchoalvolear lavage of patients with post COVID ILD (Chambers, Porter) 
• Molecular imaging as a biomarker for patient stratification and treatment response in ILD  
• Early phase clinical Trials in ILD through the NIHR Clinical Research Facility at UCLH 
• Later phase clinical trials in ILD in collaboration with UCLH and NIHR Biomedical Research Collaboration 
• Clinical trials in home monitoring in ILD: device studies, wearable technology for diagnosis and monitoring using non-linear analysis 
• Advanced computational image analysis tools for lung CT scan quantification 
• Hyperpolarised MRI techniques to improve the characterisation of lung disease 
• Experimental Medicine Initiative to Explore New Therapies (EMINENT) consortium (led by Chambers), a collaborative network that brings together investigators from UCL, Cambridge, Glasgow, Newcastle, Imperial College and GlaxoSmithKline (GSK), to conduct experimental medicine studies aimed at enhancing understanding of lung disease 
• Lung tissue pipeline with primary cell cultures, human precision-cut lung slice models and lung organoids 
• Robot assisted relatively non-invasive cryoscopic lung biopsy allows safer access to lung biopsy tissue and integration with multi-omics.