Publications

Journal article

Khor YH, Luppi F, Adegunsoye A, Collins BF, Farrand E, Montesi SB, Newton CA, Cottin V, Johannson KA, Kaul B, Kolb M, Kreuter M, Molyneaux PL, Wijsenbeek MS, Antoniou K, Behr J, Bendstrup E, Collard HR, Corte TJ, Drake WP, Ferrara G, Hariri LP, Hogaboam CM, Jenkins RG, Kaminski N, Kazerooni EA, Keane MP, Kondoh Y, Lee JS, Luo F, Maher TM, Martinez FJ, Moodley Y, Richeldi L, Sebastiani M, Sime PJ, Stowasser S, Tomassetti S, Wells A, Ryerson CJ, Podolanczuk AJet al., 2026,

Acute exacerbation in fibrotic interstitial lung disease: An International Working Group Report.

, Am J Respir Crit Care Med

Acute exacerbations (AEs) occur both in patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic interstitial lung disease (fILD). These events confer high morbidity and mortality, with a lack of proven effective therapeutic interventions. The objective of this state-of-the-art document is to summarize latest evidence since the 2016 international working group report on AE-IPF, expanding it across the spectrum of all fILDs. A comprehensive literature review on the epidemiology, associated and risk factors, prognosis, and management of AE-fILD is summarized. In addition to revising the AE definition and diagnostic criteria for broad application across different fILDs, a conceptual framework for acute respiratory worsening (ARW) has been proposed to encompass a variety of acute respiratory deteriorations, both related and unrelated to AE. This allows structured evaluation in both clinical and research settings. The proposed revised definition for AE-fILD is an acute respiratory event characterized by increased respiratory symptoms or signs and associated with radiologic or histologic features consistent with diffuse alveolar damage (with or without superimposed organizing pneumonia) in a patient with known or newly diagnosed fILD. On the other hand, ARW refers to a heterogeneous group of clinical events with acute symptom worsening not attributable to DAD in patients with fILD, such as pulmonary edema, bronchitis, and pneumonia, although severe pneumonia can trigger AE-fILD. Additionally, we discuss considerations for inclusion of AE as a clinical trial endpoint, as well as research priorities for advancing knowledge on the pathogenic mechanisms, event prediction, risk stratification, and development of drugs and supportive treatments.

Journal article

Gao C, Meng X, Chen X, Yang L, Ibrahim T, Toghani A, Yuen ELH, Eilmann N, King F, Li K, Wang L, Sun B, Wang Y, Bozkurt TO, Dong Set al., 2026,

Surface immune signaling unlocks NLR activation through mRNA alternative splicing.

, Science, Vol: 393, Pages: 65-70

Plants activate pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) to combat pathogens. However, how these systems coordinate immune activation while preventing autoimmunity remains poorly understood. In this study, we uncovered a regulatory mechanism in which surface immune signaling unlocks nucleotide-binding leucine-rich repeat (NLR) immune receptor activation through mRNA splicing. We identified an N-terminal prodomain in the potato late blight resistance protein Rpi-vnt1.1 that inhibits resistosome formation, preventing potential autoactivation of this NLR. Upon pathogen perception, PTI signaling induced alternative splicing of Rpi-vnt1.1 mRNA, removing this inhibitory element. This primed Rpi-vnt1.1 for activation by the Phytophthora infestans effector AVRvnt1, enabling resistosome assembly and immune signaling. The widespread conservation of N-terminal extensions in coiled coil-type NLRs points to a common regulatory mechanism in preventing potential autoactivation while preserving pathogen sensitivity.

Journal article

Odenkirk MT, Chaparro JM, Montgomery NT, Leaptrot KL, Sherrod SD, May JC, van Eekelen H, Schipper B, Chaura J, Velez GE, Chathiran W, Michel CR, Doenges KA, Reisdorph R, Maeda-Yamamoto M, Valdiviez L, Keshet U, Wells J, Mackell S, Bell D, Tapia Leiva S, Partridge S, Rago D, Ahonen L, Ito Y, Read ML, Evans JC, Gruszczynski MJ, Szalach L, Boyko SC, Watkins S, Ledesma Amaro R, Fiehn O, Reisdorph N, Srichamnong W, Jaramillo-Botero A, de Vos RCH, Hall RD, McLean JA, Broeckling CD, Prenni JEet al., 2026,

Correction to “Multi-laboratory assessment reveals variable ion species profiles in electrospray ionization mass spectrometer”

, Journal of the American Society for Mass Spectrometry, Vol: 37, Pages: 1683-1684, ISSN: 1044-0305

We are requesting a correction of inaccurate author affiliations. Specifically, the correct affiliation for Juliana Chaura, Gabriel Esteban Velez, and Andres Jaramillo-Botero should be iÓMICAS Research Institute, Pontificia Universidad Javeriana, Cali 760031, ColombiaThe correct author list and affiliations are shown in the Author Information with this Correction.

Journal article

Chen H, Peng H, Ellis T, Ledesma Amaro Ret al., 2026,

Programmable cell–cell adhesion in synthetic yeast communities for improved bioproduction

, Nature Chemical Biology, Vol: 22, Pages: 1057-1066, ISSN: 1552-4450

In multicellular systems, engineering-controlled cell–cell adhesion and metabolic interdependence are vital for developing complex functionalities. This study introduces a yeast synthetic toolbox for modular cell–cell adhesion and cocultures, aiming to overcome the limitations of existing approaches that lack genetic specificity and control. First, a model yeast strain 007Δ is created with seven main flocculation and agglutination genes removed, providing a clean background for synthetic adhesion systems. Then, three distinct adhesion pair systems—Strategy 1, Strategy 2.1 and Strategy 2.2—are established involving yeast flocculation and agglutination proteins and yeast surface display systems. In addition, a quantitative assessment is conducted on the adhesive specificity and strength, alongside the capability of synthetic adhesion to generate patterns. Finally, we successfully demonstrate enhanced bioproduction of the high-value food antioxidant, resveratrol, utilizing synthetic cocultures coupled with cell adhesion systems. We anticipate that this toolkit will emerge as a valuable resource for diverse applications in synthetic biology and biomanufacturing.

Journal article

Sun M, Ye B, Zhao Y, Ledesma-Amaro R, Eshboev F, Gao AX, Wang Pet al., 2026,

5'-End Translationalization: Iterative Assembly of Leaderless Polycistronic Amplifiers for Context-Independent Expression in the Food-Grade Bacterium Corynebacterium glutamicum.

, J Agric Food Chem, Vol: 74, Pages: 19859-19870

Corynebacterium glutamicum is a crucial food-grade (GRAS) bacterial chassis widely utilized for the industrial production of amino acids and nutraceuticals. However, the efficient production of recombinant proteins and secondary metabolites in this host remains limited by context dependence and low translational efficiency. To overcome this, we introduce a 5'-end translationalization strategy. By repurposing passive 5' untranslated regions (5'UTRs) into actively translated fore-cistrons, we converted conventional monocistronic designs into context-independent, leaderless polycistronic designs (PCDs). This assembly of concatenated fore-cistrons functions as a translational amplifier, largely decoupling protein output from mRNA abundance. We validated this platform by optimizing two biomanufacturing paradigms: achieving a 4.07-fold enhanced secretion of OmlA, a porcine vaccine antigen, and boosting biosynthesis of the food-grade pigment indigoidine to 1.20 g/L (a 7.33-fold increase over baselines). Together, this framework establishes a versatile, portable toolkit to overcome translational bottlenecks, enabling robust hyperproduction of recombinant proteins and engineered metabolites in biotechnology.

Journal article

Downey DG, Schulze I, Eich A, Singh D, Larbig M, Vit O, Nicolas LB, Chotirmall SH, Chalmers JDet al., 2026,

Safety and antimicrobial efficacy of CSL787, a novel nebulized IgG therapy, in patients with bronchiectasis: results from a randomized phase 1 trial.

, Am J Respir Crit Care Med, Vol: 212, Pages: 1643-1646

Journal article

Denning DW, Rogers TR, Takazono T, Su X, Lagrou K, White PL, James DA, Bafadhel M, Lopez JB, Bulpa P, Chotirmall SH, Gago S, Ortega JG, Halpin DMG, Han MK, Hurst JR, Imbert S, Janssens W, Kosmidis C, Mathioudakis AG, Ray A, Roche N, Sun Y, Tiew PY, Vogelmeier CF, Wilkinson TM, Vestbo Jet al., 2026,

Diagnostic criteria for invasive pulmonary aspergillosis in COPD patients.

, Am J Respir Crit Care Med, Vol: 212, Pages: 1913-1928

Over 400 million people have chronic obstructive pulmonary disease (COPD), with exacerbations representing a major health burden. Although the overall incidence of invasive pulmonary aspergillosis (IPA) in patients with COPD with hospitalised exacerbation is only 1 to 4%, certain factors substantially increase this frequency. Risk factors compromising defences against Aspergillus spp in COPD patients include systemic or high-dose inhaled corticosteroids, comorbidities including bronchiectasis, diabetes, and cardiovascular disease, and prolonged courses of antibiotics. An international group of experts met to develop criteria for diagnosing IPA based on existing literature and consensus in non-ventilated COPD patients. The preliminary diagnostic recommendations were further evaluated by additional experts using the Delphi methodology. A hospitalized exacerbation of COPD with two or more of the above clinical risk factors should prompt 1) a CT scan of the chest, 2) sending a respiratory sample (sputum, induced sputum or bronchoscopy sample) for direct microscopy for fungi, high volume fungal culture and preferably Aspergillus PCR, and if a bronchoscopy sample is obtained then also Aspergillus antigen (galactomannan), 3) a serum sample for galactomannan and Aspergillus IgG. The combination of a high-risk COPD patient, with compatible imaging abnormalities and any two positive tests (two samples or different tests on the same respiratory sample) for Aspergillus is sufficient to establish the diagnosis of IPA with enough confidence to initiate antifungal therapy and/or enroll the patient in a clinical or epidemiological study of IPA in COPD. Additional studies are required to augment performance data for most assays in COPD and validate the proposed diagnostic criteria.

Journal article

Yu Y, Lu R, Sun M-L, Lin L, Ledesma-Amaro R, Wang K, Ji X-J, Huang Het al., 2026,

Single cell oil enriched in ricinoleic acid biosynthesis from glucose via metabolically rewired oleaginous yeast.

, Metab Eng, Vol: 96, Pages: 80-91

Ricinoleic acid, an industrially high-value hydroxy fatty acid traditionally sourced from castor seed oil. However, plant-based production is plagued by challenges such as inherent toxicity, environmental risks, and unstable supply. Microbial biosynthesis provides a safer and more sustainable alternative, eliminating the need for land cultivation, shortens production cycles, and mitigates the toxicity risks associated with castor seed harvesting. Furthermore, microbial production of ricinoleic acid in the form of single cell oil (SCO) confers significant advantages over free fatty acid, including enhanced stability and reduced cytotoxicity. In this study, the oleaginous yeast Yarrowia lipolytica was metabolically rewired via a multi-pronged strategy: boosting the synthesis of oleoyl-CoA (the precursor of ricinoleic acid), mimicking plant acyl editing to refine phosphatidylcholine pool precursors, promoting the assembly of ricinoleic acid into storage triacylglycerols, and suppressing competing degradation pathways. Employing this integrated engineering approach, the final engineered strain YY-20 accumulated 729.4 mg/L of ricinoleic acid in shake flask cultures, accounting for 28.3% of total fatty acids. More notably, fed-batch fermentation in a bioreactor achieved a record-high ricinoleic acid titer of 6.0 g/L (comprising 26.1% of total fatty acids), accompanied by 22.8 g/L of SCO and a lipid content of 37.3% dry cell weight. These results demonstrate the efficacy of coordinated lipid pathway engineering in establishing Y. lipolytica as a robust microbial cell factory for hydroxy fatty acid production. The high SCO titer and efficient ricinoleic acid synthesis underscore the potential of this platform for the scalable industrial biomanufacturing of ricinoleic acid and other high-value unusual fatty acids.

Journal article

Davies JC, Bakkeheim E, Chansard A, Drevinek P, Dubois C, Matthews J, Sheremet M, Smith Cet al., 2026,

Perspective of the European Cystic Fibrosis Society on Improving Global Cystic Fibrosis Care.

, Pediatr Pulmonol, Vol: 61

INTRODUCTION: Outcomes for people with the inherited disease, cystic fibrosis, have improved greatly over the last few decades, but one result of this is a widening gap between regions with high income and well-resourced healthcare systems and low/middle income countries. The gap stretches from newborn screening programs, provision of standard diagnostics and genetic testing through to access to standard of care therapies. METHODS AND RESULTS: This paper describes the various initiatives of the European Cystic Fibrosis Society: our Patient Registry, a Twinning Program linking centers from different regions and our Educational Program. CONCLUSIONS: The European Cystic Fibrosis Society recognizes this as a major issue and seeks through these programs to support colleagues, patients and families in low/middle income countries.

Journal article

Hull RC, Liu Y, Cao Z, Xuan KTL, de Lima Headley DA, Richardson H, Hennayake C, Lind H, McIntosh E, Pollock J, Hughes C, Viligorska K, Choi H, Gao Y, Chotirmall SH, Shoemark A, Robertson K, Burgel P-R, Vendrell M, Xu X, Qu J-M, Song Y, Guan W-J, Chen R, Singh S, Talwar D, Mohan BVM, Tripathi SK, Swarnakar R, Trivedi S, Goeminne PC, Shteinberg M, De Soyza A, Altenburg J, Haworth CS, Sibila O, Polverino E, Loebinger MR, Ringshausen FC, Mertsch P, Lorent N, Dimakou K, Mendez R, Mclaughlin AM, Borrill Z, Lord R, Finch S, Blasi F, Burr L, Crisafulli M, Keating R, Middleton PG, Long MB, Aliberti S, Morgan L, Dhar R, Chalmers JD, Xu J-F, EMBARC, EMBARC India, Australian bronchiectasis registry and BE-Chinaet al., 2026,

Comorbid diabetes disease severity and microbial changes in patients with bronchiectasis: a combined analysis of data from the EMBARC, EMBARC-India, Australian, and BE-China registries.

, Lancet Respir Med, Vol: 14, Pages: 620-632

BACKGROUND: Bronchiectasis and diabetes commonly coexist and are associated with immune dysfunction and increased susceptibility to infection. Although diabetes is associated with worse prognosis in cystic fibrosis-related bronchiectasis, data are scarce for its impact on non-cystic fibrosis bronchiectasis. This study aimed to characterise the impact of diabetes on clinical outcomes and microbial and inflammatory profiles in patients with bronchiectasis. METHODS: This analysis comprised data from the European Bronchiectasis Registry (EMBARC), Respiratory Research Network of India (EMBARC-India), Chinese Bronchiectasis Registry (BE-China), and Australian Bronchiectasis Registry (ABR); 30 263 patients with CT-confirmed bronchiectasis in 33 countries were included in the analysis: 16 963 from EMBARC (Jan 12, 2015, to April 12, 2022), 2361 from EMBARC-India plus additional Asian countries (June 1, 2015, to Sept 1, 2017), 10 324 from BE-China (Jan 10, 2020, to March 31, 2024), and 615 from the ABR (March 7, 2016, to Sept 11, 2018). Clinical data were compared between patients with and without diabetes. Long-term outcome data were available in EMBARC and EMBARC-India. Microbiome and inflammatory profiles were characterised in a sub-cohort of EMBARC patients by sputum 16S rRNA sequencing (n=433) and serum Olink (n=479). FINDINGS: 2487 (8·2%) of 30 263 patients with bronchiectasis had diabetes. Patients with diabetes had a higher prevalence of comorbidities than those without diabetes, including cardiovascular disorders (53·5% vs 21·8%, p<0·0001), asthma (27·5% vs 21·0%, p<0·0001), and chronic obstructive pulmonary disease (34·3% vs 19·0%, p<0·0001). Patients with diabetes had more severe disease than those without diabetes, with higher Bronchiectasis Severity Index scores (8 [IQR 5-12] vs 7 [4-10], p<0·0001) and UK Medical Research Council (MRC) dyspnoea scores (p<0·0001) and

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