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We are interested in how immunological responses impact on mechanisms of lung injury and repair.

Macrophages in IPF lungs

Our projects are divided into mechanistic and translational studies. Broadly, the programme has two aims – (1) to understand the contribution of myeloid cells to lung immunopathology and fibrosis and (2) to bring new treatment and improved management to patients with fibrotic lung diseases focusing on idiopathic pulmonary fibrosis (IPF) and fibrotic sarcoidosis.

 

Contribution of myeloid cells to lung immunopathology

This part of our programme focuses on the immunobiology of myeloid cells and underpins our clinical studies.

In the last few years major strides have been made in understanding the biology of macrophages in the lungs. For example, it is now well established that there are two major types of macrophages – that derived from the bone marrow (monocyte-derived macrophages), and those that originate from the yolk sac at birth (resident alveolar macrophages), the latter endowed with self-renewing properties.  However the functions of these macrophages in health, and their contribution to disease are not clear. In addition, although the functional plasticity of the macrophages is evident, the signals that influence the development and activity of these functional subsets are unclear. This part of our programme examines these questions, and provides the basis for potential targeting of the monocyte-macrophage pathway for new therapeutics. Current projects include baseline subtyping of macrophages in health and disease, to transcend current categorization of these cells (eg M1 M2). We use scRNA sequencing and functional typing in murine models of lung fibrosis and human samples from IPF and fibrotic sarcoidosis.  We have a particular interest in understanding how viral infections (eg influenza) impact on lung fibrosis.

 

New treatment and improved management of patients with fibrotic lung diseases.

IPF is a devastating lung disease with a median survival of less than 5 years from diagnosis, worse than many cancers. Current treatment (only two) merely reduces the rate of progression of disease but does not halt worsening and scarcely increased the number of surviving years. The course of disease is punctuated by episodes of accelerated fibrosis (called AE-IPF) which heralds death as patients diagnosed with such episodes have an 80% mortality within 3 months. Major advances have been made over the last decade in understanding the mechanisms of the disease, though very little work has focused on this phase of accelerated fibrosis We are concentrating our efforts on understanding the cause, preventing and improving the outcome from AE-IPF. In recent years, we have shown that levels of monocytes correlated with amount of fibrosis in lungs of IPF patients, and are particularly high in patients with AE-IPF. We  are particularly interested in understanding the role of monocyte in AEIPF and also as biomarkers to detect the onset of this phase of disease. In addition, we have a priority in working in the lungs of IPF patients to understand the role of different groups of lung macrophages in fibrogenesis.

The group also has a major interest in studies on mechanisms of fibrosis in pulmonary sarcoidosis, a T cell mediated granulomatous disease. Studies in this sphere form an integrated research programme embedded within the Oxford Sarcoidosis Clinical Service.

We work closely with our industrial partners at the interface of disease mechanisms and drug development, and with our clinical colleagues at the Oxford Interstitial Lung Disease Service providing a flow through from mechanistic bench science to patient care.

 

Clinical research

Our bench-to-clinic research studies and governance is supported by a network of research nurses led by Simona Fourie and Jennifer McLellan. 

Our team

Selected publications