Elucidating the role of  tissue-resident immune cells in alveolar epithelial regeneration and lung fibrosis

Potential applicants with at least a 2:1 in their first degree, are invited to email Prof Ho to discuss this project. 

The lung is a distinct organ in terms of regeneration and self-renewal. In the steady-state, cell turnover is low, but after injury, it possesses tremendous ability to regrow its epithelium - a whole new lung segment can regenerate after partial pneumonectomy. Yet, in chronic lung disease e.g. idiopathic pulmonary fibrosis (IPF), regeneration is rare or occurs abnormally. The project examines the role of tissue-resident immune cells (innate lymphoid cells, Tregs, resident alveolar macrophages) in maintaining steady-state quiescence and coordinating appropriate repair after injury of the alveolar epithelium. The work will focus on the use of spatial transcriptomics to examine the in situ changes in tissue resident immune cells in the lungs,  its co-localisation with regenerating alveolar epithelium and alveolar progenitor cells during injury and regeneration/repair. There will be an emphasis on functional studies using alveolar organoids.

Contact details: Ling-pei.ho@imm.ox.ac.uk

See our Spotlight video - https://youtu.be/Dj0uNQgA1Fs

My research group studies how immunological responses impact on mechanisms of lung injury, regeneration and repair. Our projects are divided into mechanistic and translational studies. We have two aims – (1) to understand the contribution of immune cells to chronic progressive lung fibrosis and alveolar regneration (2) to use this knowledge to bring new treatment and improved management to patients with fibrotic lung diseases,focusing on idiopathic pulmonary fibrosis (IPF) and fibrotic sarcoidosis. 

We focus on both the lung tissue and blood in human studies, and longitudinal murine studies. In the lungs, we have developed methods (with mathematicians) to map out the spatial organisation of immune cells using mathematical tools, single cell imaging mass cytometry and single cell transcriptomics. 

Dr Jeongmin Woo 

Dr Neda Hasan

Mr Chaitanya Vuppusetty (Lab manager)

Dr Praveen Weeratunga 

Dr Harry Tian Hu

Dr Vishal Nathwani 

Dr Sabrina Zulfikar 

Dr Leila Bagha

Affiliates

Prof Daisy Yuejuan Zheng

Dr Andrew Achaiah

Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs.   Weeratunga P, Denney L, Bull J, Repapi E,  Sergeant M, Etherington E,  Vuppussetty C, Turner G,  Clelland C, Woo JM, Cross A, Issa F, de Andrea CE,  Bermejo IM, Sims D,  McGowan S,  Zurke YX, Ahern DJ, Gamez EC, Whalley J, Richards D, Klenerman P, Monaco C, Udalova IA, Dong T, Antanaviciute A, Ogg G, Knight JC, Byrne HM,  Taylor S, Ho L.P. Nature Comms 2023; 14, 7216.

Immune mechanisms of granuloma formation in sarcoidosis and tuberculosis. Weeratunga P, Moller DR and Ho LP. J Clin Invest 2024 134 (1):e175264

Temporo-spatial cellular atlas of the regenerating alveolar niche in idiopathic pulmonary fibrosis. Weeratunga P, Hunter B, Sergeant M, Bull J, Clelland C, Denney D, Vuppusetty C, Burgoyne R, Woo JM, Hu T, Borthwick L, Shaw J, Antanavicuete A, Filby A, Byrne HM, Fisher A and Ho L.P. MedRxv 2024; https://doi.org/10.1101/2024.04.10.24305440

COVID-19 therapeutics: Challenges and directions for the future. Robinson PC, Liew DFL, Tanner HL, Grainger JR, Dwek RA, Reisler RB, Steinman L, Feldmann M, Ho L.P., Hussell T, Moss P, Richards D, Zitzmann N. Proc Natl Acad Sci U S A. 2022;119:e2119893119.

Multi-modal characterization of monocytes in idiopathic pulmonary fibrosis reveals a primed type I interferon immune phenotype. Fraser E, Denney L, Blirando K, Vuppusetty C, Antanviciute A, Zheng Y, Repapi E, Iotchkova V, Ashley N, St Noble V, Benamore R, Hoyles R, Clelland C, Rastick JM, Hardman CS, Alham NK, Rigby RE, Rehwinkel J, Ho L.P. Frontiers Immunology 2021;12:623430.

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity. COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium. Cell. 2022;185(5):916-938.e58. 

Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Monk P, Marsden R, Tear V, Brookes J, Batten TTN, Mankowski M, Gabbay F, Davies D, Holgate S, Ho L.P, Clark T, Djukanovic R, and Wilkinson T. Lancet Respiratory Medicine. 2020, 12;S2213

Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19.  Mann E, Menon M, Knight S, Konkel J, Jagger C, Shaw T, Krishnan S, Rattray M, Ustianowski A, Bakerly ND, Dark P, Lord G, Simpson A, Felton T, Ho L.P, NIHR Respiratory TRC, Feldmann M, CIRCO, Grainger J, Hussell T. Science Immunology. 2020, 5;51

Immune mechanisms in fibrotic pulmonary sarcoidosis. Weeratunga P, Moller DR, Ho L.P. Eur Respir Rev 2023; 31 (166).

Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury.Cross, A. R., C. E. de Andrea, M. Villalba-Esparza, M. F. Landecho, L. Cerundolo, P. Weeratunga, R. E. Etherington, L. Denney, G. Ogg, L. P. Ho, I. S. Roberts, J. Hester, P. Klenerman, I. Melero, S. N. Sansom and F. Issa (2023).  J Clin Invest Insight 2023; 8(2):e157837

M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza. SL Cole, J Dunning, WL Kok, KH Benam, A Benlahrech, E Repapi, F Martinez, L Drumright, TJ Powell, M Bennett, R Elderfield, MOSAIC Investigators, T Dong, J McCauley, EFY Liew, S Taylor, W Barclay, V Cerundolo, PJ Openshaw, AJ McMichael and L.P Ho. J Clin Invest Insight 2017; 6;2:e91868

Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial. Fisher BA, et al. Lancet Respir Med. 2022;10(3):255-266. 

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study. PHOSP-COVID Collaborative Group. Lancet Respir Med. 2022:S2213-2600(22)00127-8.

Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences. F Martinez, L Helming, R Mueller, A Varin, B Melgert, C Draijer, B Thomas, M Fabbri, A Crawshaw, L.P Ho, N Ten Hacken, V Jiménez, N Kootstra, J Hamann, D Greaves, M Locati, A Mantovani and S Gordon. Blood 2013; 28;121(9):e57-69.

Gene-set Analysis of Lung Samples Provides Insight into Pathogenesis of Progressive, Fibrotic Pulmonary Sarcoidosis. HE Lockstone, Sanderson S, Kulakova N, Baban D, Leonard A, Kok WL, McGowan S, McMichael AJ, Ho LP. Am J Respir Crit Care Med. 2010;181(12):1367-75.