Professor of Allergy and Respiratory Genetics, Associate Dean, Research
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Professor John Holloway is Professor of Allergy and Respiratory Genetics within Medicine at the University of Southampton.
John Holloway graduated with a B.Sc. in Biochemistry from Otago University, New Zealand in 1992. He undertook research based at both the University of Southampton and the Malaghan Institute (Wellington, New Zealand) into the genetic basis of asthma graduating with a Ph.D. from Otago University in 1997. In 1997 Professor Holloway returned to Southampton and together with Professor Stephen Holgate continued his research into the genetic basis of allergies and asthma. He now heads the Respiratory Genetics Group, based in the Human Development and Health and Clinical and Experimental Sciences Schools. The Respiratory Genetics Group undertakes a number of research projects into the genetic basis of allergy, asthma and other respiratory diseases. Research highlights include the identification of the gene ADAM33 as an asthma susceptibility gene (Nature 2002; 418:426) as a result of a collaborative project with Genome Therapeutics Corporation (Waltham, MA, USA) and Schering-Plough. More recently his work has focused on the genetic and epigenetic basis for the role of early life in determining susceptibility to these conditions.
Professor Holloway was appointed to a personal chair in the Faculty of Medicine in 2011. As well as his on-going research, he contributes to Clinical Pharmacology and Molecular Cell Biology teaching as part of the Bachelor of Medicine program.
Details of Professor Holloway's publications can be found here.
Qualifications
BSc (Hons), Biochemistry, University of Otago 1992 PhD, University of Otago 1997 PG Cert (Academic Practice), University of Southampton 2006
Appointments held
Postdoctoral Research Fellow in Respiratory Cell & Molecular Biology and Human Genetics Divisions, University of Southampton. 1997-2001
Senior Research Fellow Human Genetics, and Infection, Inflammation & Repair Divisions, University of Southampton 2002-2004
Lecturer, Infection, Inflammation & Repair Division, School of Medicine, University of Southampton. 2005 – 2008
Reader, Infection, Inflammation and Immunity and Human Genetics Divisions, School of Medicine, University of Southampton. 2008 – 2011
Professor of Allergy and Respiratory Genetics, Human Development and Health, Faculty of Medicine, University of Southampton. 2011 - present
Associate Dean Enterprise and International, Faculty of Medicine 2013 - 2015
Associate Dean Research, Faculty of Medicine 2015 - present
Research
Responsibilities
Publications
Teaching
Contact
Research interests
Professor Holloway’s interests are in the role of genetics and epigenetics in the developmental origins of allergy and respiratory disease.
Exploring the mechanisms of prenatal programming of respiratory disease
Disordered growth during early life has been shown to result in chronic diseases such as diabetes and coronary disease in later life. Environmental factors such as unbalanced nutrition before birth result in metabolic and structural adaptations that lead to persistent modifications to offspring phenotype, i.e. fetal programming. There is evidence that respiratory disease is also influenced by fetal programming. Asthma has been linked epidemiologically with markers of fetal growth such as anthropometric measurements at birth. Reduced fetal growth and duration of gestation are associated with impaired lung development in children. Airway function at birth is also a significant predictor of asthma, adult lung function, and possibly COPD. In collaboration with Dr Christopher Torrens we are investigating the effects of maternal under-nutrition on lung development in a maternal protein restriction model. We have shown that there are persistent alterations in gene and miRNA expression in response to maternal protein restriction demonstrating that in utero environmental exposures result in altered lung development and persistent phenotypic changes.
Epigenetic mechanisms underlying atopy and asthma susceptibility
It is believed that a genetic predisposition, along with exposure to environmental factors, alters the risk for asthma and atopy. Research over the previous decade has provided some insight into the role of specific DNA polymorphisms, however, little is known about the epigenome, which is considered to establish when and where the blueprint of the DNA is expressed. 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 (pregnancy, infancy, or both) are epigenetic marks established? Addressing these questions will critically impact the prevention and treatment of asthma and allergies. In partnership with Professor Wilfried Karmaus and Assoc. Professor Hongmei Zhang (University of Memphis), Professor Susan Ewart and Professor Linda Mansfield (Michigan State University) and Professor Hasan Arshad, we are attempting to answer these questions in the Isle of Wight longitudinal birth cohort by examining genome-wide DNA methylation in women of the cohort and recruiting their children as the second generation in this cohort.
In collaboration with Professor Seif Shaheen (QMUL) we are undertaking a pilot study of genome wide DNA methylation in match samples of blood, buccal, nasal, and lung epithelial DNA in children with and without atopy. By examining the correlation of methylation patterns between these tissue sources, this should establish the validity of analysing methylation in DNA derived from these sources in large epidemiological cohorts in relation to asthma in the future.
Gene-environment interactions in the early life origins of asthma
In collaboration with colleagues at the University of Bristol (Professor John Henderson), and Queen Mary’s University of London (Professor Seif Shaheen), we are studying how relevant gene polymorphisms in the mother and child modify effects of prenatal and postnatal exposure to tobacco smoke, paracetamol and antioxidants on childhood lung function, wheezing, asthma and bronchial hyper-responsiveness, in a large population-based birth cohort. Confirmation of interactions between oxidant/antioxidant exposures and gene variants which influence antioxidant function and xenobiotic toxicity would provide stronger evidence that the effects of the environmental risk factors are causal, and may provide insights into mechanisms. By increasing our understanding of the early life influences on lung development we hope to devise new strategies aimed at the primary prevention of lung disease in children and the optimisation of their respiratory health. This work has provided evidence that prenatal paracetamol (acetaminophen) exposure may predispose the developing infant to subsequent development of asthma through mechanisms dependent on oxidative stress (Shaheen et al. JACI 2010). We are now hoping to extend our studies of prenatal gene-environmental interactions in lung development by examining the effects of prenatal nutrition.
BMBS COST Action BM1201: Developmental Origins of Chronic Lung Disease
Professor Holloway is Vice-chair (Chair Dr Susanne Kraus-Etschman, CPC Munich) of the BMBS COST Action network: Developmental origins of Chronic Lung Disease. Chronic lung diseases (CLD) are a major cause of death in the Western world but curative therapies do not exist. Recent studies indicate that the risk to develop CLD is modified by early exposures during critical developmental windows. This concept opens unique opportunities for the pre- or early postnatal modification of later disease risks, but the underlying molecular mechanisms are largely unexplored. To close this gap, a highly cross-disciplinary approach involving scientists from basic and clinical research is required. Several European institutions study early origins of CLD with adequate national funding, but these efforts are not integrated and lack a comprehensive platform for synergistic collaboration. This COST Action will allow the creation of a coordinated and highly translational research program. This will bring forward a novel understanding of CLD pathogenesis and build the prerequisites for the successful development of early interventions and/or innovative therapies.
The Holloway laboratory also participates in a number of national and international consortia investigating the genetics of allergy and respiratory disease. Further details can be found at http://www.respiratorygenetics.org.uk/
2004 Athanasios Konstantinidis PhD 2006 Julie Cakebread PhD 2007 Helen North PhD 2008 Shane Sanassay PhD 2010 Ahmed Abdemotelb PhD 2010 Mathew Rose-Zerilli PhD 2012 Shelley Davis PhD 2014 Ali Ziyab PhD (University of South Carolina) 2015 Todd Everson PhD (University of South Carolina)
Member of Faculty Leadership team Chair Research Management Committee Chair web strategy group Member Joint Research Strategy Board
University of Southampton
Member Research and Enterprise Executive Group Member of Research and Academic Systems Board, member of Research Integrity Group, Member Open Access Group
National and International responsibilities
Member Asthma UK Research Review Panel Vice Chair BMBS COST Action BM1201 Developmental Origins of Chronic Lung Disease Editorial board member, Allergy (European Journal of Allergy and Clinical Immunology) Faculty Member Respiratory Pharmacology Section Faculty of 1000
Johnson, L., Shah, I., Loh, A. X., Vinall, L. E., Teixeira, A. S., Rousseau, K., ... Swallow, D. M. (2013). MUC5AC & inflammatory mediators associated with respiratory outcomes in the British 1946 birth cohort. Respirology, 18(6), 1003-1010. DOI: 10.1111/resp.12092
Yang, I. A., Savarimuthu, S., Kim, S. T., Holloway, J. W., Bell, S. C., & Fong, K. M. (2007). Gene-environmental interaction in asthma. Current Opinion in Allergy and Clinical Immunology, 7(1), 75-82.
Rose-Zerilli, M. J., Holgate, S. T., & Holloway, J. (2009). Genetics of asthma and bronchial hyperresponsiveness. In R. Panwankar, S. T. Holgate, & L. J. Rosenwasser (Eds.), Allergy Frontiers: Epigenetics , Allergens and Risk Factors (pp. 161-188). Tokyo, Japan: Springer.
BM4 and BM5: Contributes to Molecular Cell Biology teaching in years 1-3 of the Bachelor of Medicine program giving lectures, taking tutorials and organising symposia and practical classes
Personal Tutor
Postgraduate Taught: Lectures on MSc Allergy and MSc Medical Genomics courses and on the Integrated PhD Infection and immunity pathway
Professor John Holloway Faculty of Medicine University of Southampton Duthie Building Mailpoint 808 Southampton General Hospital Tremona Road Southampton SO16 6YD
