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Studying the contribution of the immune system to lung injury, repair and fibrosis.

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About the Research

We work on the mechanisms of lung injury, repair and fibrosis, with a particular focus on how monocytes and macrophages influence these processes. Our current focus is on how monocyte-derived macrophages contribute to lung fibrosis and we have also begun studies on how lung resident cells influence repair and regeneration. We use murine models, single cell genomics, mass and advanced flow cytometry to explore our questions.

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 end stage lung disease idiopathic pulmonary fibrosis (IPF), regeneration is rare or occurs abnormally. The project offered 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 improved bleomycin murine model to examine the in vivo 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. Findings will be tested in the appropriate transgenic mice and human diseased lungs in collaboration

 

Training Opportunities

The group currently use these methods routinely to explore our scientific hypotheses: murine models of lung injury and repair, multi-colour flow cytometry, CYTOF, single cell genomics, immunohistochemistry, and standard qPCR, Western blots and tissue culture.

 

Students will be enrolled on the MRC WIMM DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide-range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

All MRC WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the MRC WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework. The RDM also holds an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

 

Publications

M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza.  Cole SL, Dunning J, Kok WL, Benam KH, Benlahrech A, Repapi E, Martinez FO, Drumright L, Powell TJ, Bennett M, Elderfield R, Thomas C; MOSAIC investigators, Dong T, McCauley J, Liew FY, Taylor S, Zambon M, Barclay W, Cerundolo V, Openshaw PJ, McMichael AJ, Ho LP. JCI Insight. 2017;2(7):e91868.

Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza. Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ; MOSAIC Investigators, Moffatt MF, O'Garra A, Openshaw PJM. Nat Immunol. 2018;19(6):625-635

Epithelial-derived TGF-β1 acts as a pro-viral factor in the lung during influenza A infection.  Denney L, Branchett W, Gregory LG, Oliver RA, Lloyd CM. Mucosal Immunol. 2018;11(2):523-535.

Pulmonary Epithelial Cell-Derived Cytokine TGF-β1 Is a Critical Cofactor for Enhanced Innate Lymphoid Cell Function. Denney L, Byrne AJ, Shea TJ, Buckley JS, Pease JE, Herledan GM, Walker SA, Gregory LG, Lloyd CM.Immunity. 2015;43(5):945-58.

Supervisors