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  • Journal article
    Bui LT, Winters NI, Chung M-I, Joseph C, Gutierrez AJ, Habermann AC, Adams TS, Schupp JC, Poli S, Peter LM, Taylor CJ, Blackburn JB, Richmond BW, Nicholson AG, Rassl D, Wallace WA, Rosas IO, Jenkins RG, Kaminski N, Kropski JA, Banovich NEet al., 2021,

    Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity

    , NATURE COMMUNICATIONS, Vol: 12
  • Journal article
    Hopkinson NS, Jenkins G, Hart N, 2021,

    COVID-19 and what comes after?

    , THORAX, Vol: 76, Pages: 324-325, ISSN: 0040-6376
  • Journal article
    Dhindsa RS, Mattsson J, Nag A, Wang Q, Wain L, Allen R, Wigmore EM, Ibanez K, Vitsios D, Deevi SVV, Wasilewski S, Karlsson M, Lassi G, Olsson H, Muthas D, Monkley S, Mackay A, Murray L, Young S, Haefliger C, Maher TM, Belvisi MG, Jenkins G, Molyneaux PL, Platt A, Petrovski Set al., 2021,

    Identification of a missense variant in SPDL1 associated with idiopathic pulmonary fibrosis

    , Communications Biology, Vol: 4, ISSN: 2399-3642

    Idiopathic pulmonary fibrosis (IPF) is a fatal disorder characterised by progressive, destructive lung scarring. Despite substantial progress, the genetic determinants of this disease remain incompletely defined. Using whole genome and whole exome sequencing data from 752 individuals with sporadic IPF and 119,055 UK Biobank controls, we performed a variant-level exome-wide association study (ExWAS) and gene-level collapsing analyses. Our variant-level analysis revealed a novel association between a rare missense variant in SPDL1 and IPF (NM_017785.5:g.169588475 G > A p.Arg20Gln; p = 2.4 × 10−7, odds ratio = 2.87, 95% confidence interval: 2.03–4.07). This signal was independently replicated in the FinnGen cohort, which contains 1028 cases and 196,986 controls (combined p = 2.2 × 10−20), firmly associating this variant as an IPF risk allele. SPDL1 encodes Spindly, a protein involved in mitotic checkpoint signalling during cell division that has not been previously described in fibrosis. To the best of our knowledge, these results highlight a novel mechanism underlying IPF, providing the potential for new therapeutic discoveries in a disease of great unmet need.

  • Journal article
    Leavy OC, Ma S-F, Molyneaux PL, Maher TM, Oldham JM, Flores C, Noth I, Jenkins RG, Dudbridge F, Wain LV, Allen RJ, Leavy OC, Ma S-F, Molyneaux PL, Maher TM, Oldham JM, Flores C, Noth I, Jenkins RG, Dudbridge F, Wain LV, Allen RJet al., 2020,

    Proportion of idiopathic pulmonary fibrosis risk explained by known Common genetic loci in European populations

    , American Journal of Respiratory and Critical Care Medicine, Vol: 203, Pages: 775-778, ISSN: 1073-449X

    Genome-wide association studies have identified 14 genetic loci associated with susceptibility to idiopathic pulmonary fibrosis (IPF), a devastating lung disease with poor prognosis. Of these, the variant with the strongest association, rs35705950, is located in the promoter region of the MUC5B gene and has a risk allele (T) frequency of 30-35% in IPF cases. Here we present estimates of the proportion of disease liability explained by each of the 14 IPF risk variants as well as estimates of the proportion of cases that can be attributed to each variant. We estimate that rs35705950 explains 5.9-9.4% of disease liability, which is much lower than previously reported estimates. Of every 100,000 individuals with the rs35705950_GG genotype we estimate 30 will have IPF, whereas for every 100,000 individuals with the rs35705950_GT genotype 152 will have IPF. Quantifying the impact of genetic risk factors on disease liability improves our understanding of the underlying genetic architecture of IPF and provides insight into the impact of genetic factors in risk prediction modelling.

  • Journal article
    George PM, Barratt SL, Condliffe R, Desai SR, Devaraj A, Forrest I, Gibbons MA, Hart N, Jenkins RG, McAuley DF, Patel BV, Thwaite E, Spencer LGet al., 2020,

    Respiratory follow-up of patients with COVID-19 pneumonia

    , Thorax, Vol: 75, Pages: 1009-1016, ISSN: 0040-6376

    The COVID-19 pandemic has led to an unprecedented surge in hospitalised patients with viral pneumonia. The most severely affected patients are older men, individuals of black and Asian minority ethnicity and those with comorbidities. COVID-19 is also associated with an increased risk of hypercoagulability and venous thromboembolism. The overwhelming majority of patients admitted to hospital have respiratory failure and while most are managed on general wards, a sizeable proportion require intensive care support. The long-term complications of COVID-19 pneumonia are starting to emerge but data from previous coronavirus outbreaks such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) suggest that some patients will experience long-term respiratory complications of the infection. With the pattern of thoracic imaging abnormalities and growing clinical experience, it is envisaged that interstitial lung disease and pulmonary vascular disease are likely to be the most important respiratory complications. There is a need for a unified pathway for the respiratory follow-up of patients with COVID-19 balancing the delivery of high-quality clinical care with stretched National Health Service (NHS) resources. In this guidance document, we provide a suggested structure for the respiratory follow-up of patients with clinicoradiological confirmation of COVID-19 pneumonia. We define two separate algorithms integrating disease severity, likelihood of long-term respiratory complications and functional capacity on discharge. To mitigate NHS pressures, virtual solutions have been embedded within the pathway as has safety netting of patients whose clinical trajectory deviates from the pathway. For all patients, we suggest a holistic package of care to address breathlessness, anxiety, oxygen requirement, palliative care and rehabilitation.

  • Journal article
    John AE, Graves RH, Pun KT, Vitulli G, Forty EJ, Mercer PF, Morrell JL, Barrett JW, Rogers RF, Hafeji M, Bibby LI, Gower E, Morrison VS, Man Y, Roper JA, Luckett JC, Borthwick LA, Barksby BS, Burgoyne RA, Barnes R, Le J, Flint DJ, Pyne S, Habgood A, Organ LA, Joseph C, Edwards-Pritchard RC, Maher TM, Fisher AJ, Gudmann NS, Leeming DJ, Chambers RC, Lukey PT, Marshall RP, Macdonald SJF, Jenkins RG, Slack RJet al., 2020,

    Translational pharmacology of an inhaled small molecule alpha v beta 6 integrin inhibitor for idiopathic pulmonary fibrosis

    , Nature Communications, Vol: 11, ISSN: 2041-1723

    The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and disease-related end points. Here, we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy.

  • Journal article
    Molyneaux PL, Smith JJ, Saunders P, Chua F, Wells AU, Renzoni EA, Nicholson AG, Fahy WA, Jenkins RG, Maher TMet al., 2020,

    Bronchoalveolar lavage is safe and well tolerated in individuals with idiopathic pulmonary fibrosis: an analysis of the PROFILE study

    , American Journal of Respiratory and Critical Care Medicine, Vol: 203, Pages: 136-139, ISSN: 1073-449X
  • Journal article
    Leavy O, Ma S-F, Molyneaux P, Maher T, Oldham J, Flores C, Noth I, Jenkins G, Dudbridge F, Wain L, Allen Ret al., 2020,

    Proportion of idiopathic pulmonary fibrosis risk explained by known genetic loci

    Genome-wide association studies have identified 14 genetic loci associated with susceptibility to idiopathic pulmonary fibrosis (IPF), a devastating lung disease with poor prognosis. Of these, the variant with the strongest association, rs35705950, is located in the promoter region of the MUC5B gene and has a risk allele (T) frequency of 30-35% in IPF cases. Here we present estimates of the proportion of disease liability explained by each of the 14 IPF risk variants as well as estimates of the proportion of cases that can be attributed to each variant. We estimate that rs35705950 explains 5.9-9.4% of disease liability, which is much lower than previously reported estimates. Of every 100,000 individuals with the rs35705950_GG genotype we estimate 30 will have IPF, whereas for every 100,000 individuals with the rs35705950_GT genotype 152 will have IPF. Quantifying the impact of genetic risk factors on disease liability improves our understanding of the underlying genetic architecture of IPF and provides insight into the impact of genetic factors in risk prediction modelling.

  • Journal article
    Liebeck MW, Praeger CE, Saxl J, 2019,

    The classification of 3/2-transitive permutation groups and 1/2-transitive linear groups

    , Proceedings of the American Mathematical Society, Vol: 147, Pages: 5023-5037, ISSN: 1088-6826

    A linear group G ≤ GL(V ), where V is a finite vector space, is called 12-transitive if all the G-orbits on the set of nonzero vectors have the same size. We complete the classification of all the 12-transitive linear groups. As a consequence we complete the determination of the finite 32-transitive permutation groups – the transitive groups for which a point-stabilizerhas all its nontrivial orbits of the same size. We also determine the (k +12)-transitive groups for integers k ≥ 2.

  • Journal article
    Liebeck MW, Schul G, Shalev A, 2017,

    Rapid growth in finite simple groups

    , Transactions of the American Mathematical Society, Vol: 369, Pages: 2765-8779, ISSN: 1088-6850

    We show that small normal subsets A of finite simple groups growvery rapidly – namely, |A2| ≥ |A|2− , where > 0 is arbitrarily small.Extensions, consequences, and a rapid growth result for simple algebraicgroups are also given.

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