William Cookson

William Cookson is Professor of Genomic Medicine at Imperial College London and Head of Respiratory Sciences for the College. He is Head of the Asmarley Centre for Genomic Medicine at the National Heart and Lung Institute. He won a Joint Wellcome Senior Investigator Award with Professor Miriam Moffatt in 2011, and was elected to the College of NIHR Senior Investigators in 2013.

Professor Cookson initially trained as a respiratory physician, before receiving a D.Phil. in human genetics at Oxford in 1994. He was a Professor of Human Genetics at the University of Oxford between 1998 and 2004. Over the past thirty years he and Miriam Moffatt have developed a successful research group devoted to understanding the genetic causes of asthma (Zhang Y. et al., Nature Genetics 2003; Allen M. et al., Nature Genetics 2003; Moffatt M. et al., Nature 2007; Moffatt M. et al., New England Journal of Medicine 2010).

Many of the genes identified by these studies are concentrated in the airway epithelium, so that asthma is now recognised as a disease of the airway mucosa. Genes identified by the group such as ORMDL3, IL33, TSLP and IL18R1 are the focus for new asthma therapies.

In addition to detailed investigation of the functions of these major asthma genes, the group are also systematically charting inflammatory pathways by gene expression, RNA sequencing, and gene knockdowns in cellular models of inflammation. These studies are the basis for developing new therapies for asthma and mucosal inflammation (genomic pharmacology).

The group have pioneered gene expression mapping to identify the function of loci identified by genome-wide association studies. The resulting comprehensive maps of expression quantitative trait loci (eQTLs) (Dixon A. et al., Nature Genetics 2007, Liang L. et al, Genome Resarch 2013) have aided the systematic detection of genes underlying many complex disorders and have contributed to the 1000 genomes project.

A parallel strand in the group's work has been to understand at the molecular level the interactions between genes and environment, with the realistic hope that this will lead to effective prevention of the disease (Cookson, Nature 1999). Cookson was co-coordinator of the mutinational GABRIEL consortium that made many discoveries about the effects of genes and environment on asthma in Europe (Moffatt M. et al., New England Journal of Medicine 2010; Ege M. et al., New England Journal of Medicine 2011).

In the face of a prevailing wisdom that the airways of normal individuals are completely sterile, the group were first to use DNA sequencing to show that the airways contain a characteristic microbiota, and that this bacterial community is disturbed in patients with asthma and COPD (Hilty et al., PLoSOne 2010).

Studies of the airway microbiome are now a central part of the group's research, as they apply culture-independent sequencing methods to other lung diseases, including pulmonary fibrosis, cystic fibrosis and bronchiectasis. They have systematically cultured and genome-sequenced the prinicpal commensal airway bacteria, idenifying more than 50 new species, and are exploring how they interact with the airway mucosa to regulate immunity and protect against infection (Cuthbertson et al., bioRxiv 2022).

During the COVD pandemic, the number of cases of acute asthma and COPD went down by half, across the globe (Cookson W. et al., AmJRCCM 2022). This is attributable to reduced transmission of respiratory viruses and bacteria, following non-pharmaceutical interventions such as social distancing.

The public health implications are enormous (for example protecting asthmatic children in schools from rhinovirus infection). A prime driver of the group is now to find new ways of treating and preventing asthma, including antivirals, inhaled antimicrobials and vaccines.

The group are developing large-scale genomic studies of lung and pleural cancer, in collaboration with G.M. Lathrop at McGill Genome Centre in Canada, and aided by a £5mn grant from the Department of Health. They are currently sequencing multiple lung cancers to identify mutations and gene expression patterns driving disease appearance and outcomes. At the same time the group are investigating how the lung microbiome alters the growth and response to therapy of these aggressive cancers.