Professor John Holloway

Research interests

• Human genetics
• Epigenetics
• Respiratory Disease
• Allergy
• Asthma

Current research

Research interests

Professor Holloway leads an active research team based within Human Genetics and Medical Genomics theme of the School of Human Development & Health, Faculty of Medicine. His core research program focuses on the genetic and epigenetic regulation of allergy and airways disease and aims to connect the basic science of population genetic variability and epigenetic regulation of gene expression with clinical observations. The focus of his research at the basic-science - clinical interface aims to provide molecular insights into the diagnosis, treatment and prevention of common respiratory diseases.

His current research program focuses on genetics, epigenetics and functional genomics of allergic and respiratory diseases such as asthma and COPD. This includes exploring the mechanisms of prenatal programming of respiratory disease; gene-environment interactions in the early life origins of asthma and COPD; characterisation of genetic factors influencing asthma severity; and identification and validation of novel asthma susceptibility genes. This work involves significant international collaboration with major research partners in the Universities of Memphis, South Carolina and Michigan State (USA), Bergen (NOR), and Melbourne (AUS).

A current major focus is NIH funded research programs into the epigenetics of allergy and asthma. It is believed that a genetic predisposition, along with exposure to environmental factors, alters the risk for asthma and atopy. There are four major gaps in our understanding: (1) Do epigenetic modifications alter the risk for allergy and asthma? (2) Is the epigenome, in particular the methylation of CpG sites, vertically transmitted from parents to offspring? (3) What environmental factors impact epigenetic marks? (4) In which developmental periods (pre-conception, pregnancy, infancy, adolescence) are induvial most sensitive to environmentally induce epigenetic changes? Addressing these questions will critically impact the prevention and treatment of asthma and allergies. This work utilises the Isle of Wight longitudinal birth cohort by examining genome-wide DNA methylation in members of the cohort and recruiting their children as the third (F2) generation in this cohort.

Another major project is epigentic analysis in the RHINESSA study. There is emerging evidence that asthma may result from exposures before conception. Supported by animal studies, our preliminary analyses suggest that the environment before conception is important for asthma and allergies, not least the environment of future fathers, and that adolescence may be a particularly important vulnerability period. If true, this will have immense impact on public health strategies. To investigate this the RHINESSA study led by Professor Cecilie Svanes (University of Bergen) is using epidemiological and epigenetic methods to study i) determinants for asthma and allergies that operate before conception, ii) vulnerable life periods, and iii) related epigenetic mechanisms. Epigenome-wide association studies will explore identified risks and vulnerability periods, and give a biological understanding that in turn will guide new epidemiological analyses.

In addition to these activities Prof. Holloway participates in a number of national and international consortia investigating the genetics of allergy and respiratory disease. This includes the Pregnancy and Childhood Epigenetics (PACE) consortium, a collective of research groups pooling data to understand the effect of prenatal / early life environmental exposures on DNA methylation and its relationship to childhood disease, and the UNICORN study which integrates birth cohorts with patient cohorts and randomised controlled trials for joint analyses, offering opportunity for a step change in understanding mechanisms underlying different asthma endotypes.

Research projects