研究领域
Asthma and allergy and major public health problems and their prevalence are increasing. Professor Arshad’s research covers 4 linked areas; (i) epidemiology, genetic, epigenetic and environmental risk factors in asthma and allergy, (ii) Prevention of asthma and allergy, (iii) pathogenetic mechanisms in the development and persistence of asthma and allergy and (iv) prevalence and diagnosis of food allergy. His research aims to improve the understanding of the development and persistence of asthma and allergic disease and test novel strategies for primary prevention.
(i) Epidemiology, natural history, genetic and environmental risk factors and epigenetic mechanisms in the origins and progression of asthma and allergy: Professor Arshad recruited the Isle of Wight birth cohort and has overseen regular assessments of these children from birth to 18 years of age. The birth cohort participants are being assessed currently at 26 years. He oversees a programme of studies investigating gene-gene and gene-environment interactions and epigenetic regulation in the development of asthma and allergy, using the longitudinally collected cohort data and samples. These studies have been supported by several project grants from the National Institute of Health, USA. There is close collaboration with national and international groups working in this area. He holds joint grants and publications with Professor Karmaus, an epidemiologist from the University of South Carolina and Professor Ewart, a geneticist at Michigan State University. He also collaborates with investigators leading other UK birth cohorts in the STELAR project that has been funded by the Medical Research Council. Other collaborations include European network of birth cohorts such as GALEN, CHICO and MeDALL (funded by the EU).
A further project relates to the recruitment of children born to the participants of the Isle of Wight birth cohort (now aged 26) into a study investigating genetic, epigenetic, and environmental exposures in the development of asthma and allergic disease. Specifically, he is investigating if certain environmental factors influence genetic expression via epigenetic mechanism (e.g. DNA methylation), if the effect on immune responses can be passed on to the subsequent generation and what factors inhibit or reverse this process. Another aim is to predict disease development using epigenentic markers.
(ii) Primary and secondary prevention of asthma and allergy: His translational studies in this research area are funded by the National Institute of Health Research. The Isle of Wight primary prevention study was the first to test the effectiveness of a strict food and house dust mite allergen avoidance regime during infancy aimed at preventing allergic disease in high risk children. Contrary to findings of single allergen reduction strategies that have little or no clinical effect, the use of multifaceted interventions started from birth reduced allergic sensitisation and asthma by 25% to 50% (compared to control group). Another ongoing project, as part of the Respiratory Biomedical Research Unit, is investigating the effect of house-dust mite sub-lingual immunotherapy for primary prevention of asthma and allergy in high risk children. The first results of this randomised controlled trial showed a significant reduction of allergen sensitisation in the treated group at 18 months. Assessment at 3 years has just completed and 6 year assessment will commence in June 2016.
(iii) Understanding the mechanism of development and persistence of asthma. (a) Early life immune responses and development of allergic disease: As part of the Respiratory Biomedical Research Unit, 300 infants at high and 60 infants at low heredity risk of allergy were recruited from birth. In collation with LA Jolla Institute of Allergy and Immunology, we are investigating epigenetic markers associated with immune response genes that lead to the dwevelopment of asthma (b) Causes of persistence and remission of adolescent asthma: Asthma is a chronic inflammatory disorder of the conducting airways with distinct structural and functional abnormalities. In a Medical Research Council funded programme grant, adolescents from the birth cohort, with persistent and remitted asthma, were recruited and further characterized to assess airway function, bronchial responsiveness and atopy. Bronchial brushings and biopsies were obtained for immunohistochemistry and tissue engineering studies investigating activation of the EMTU and tissue remodelling in vivo and in vitro. Recently, we have won a 5 year project grant from NIH, in collaboration with University of Bristol (UK) and Memphis (USA) to study epigenetic factors in adolescent asthma.
(iv) Food/Nut allergy: Professor Arshad has investigated the prevalence, natural history and diagnosis of food allergy, particularly peanut and brazil nut allergies over two decades in collaboration with Professor Tara Dean adn Dr Carina Venter of Portsmouth University. Further studies are planned to investigate the role of component resolved diagnosis in food allergy and role of opral immunobiology as a novel treatment of food allergy.
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Multi-generational cohorts in asthma and allergy - Arshad, Hasan, Karmaus, Wilfried, Zhang, Hongmei and Holloway, John W. Published:2016Publication:Journal of Allergy and Clinical ImmunologyPage Range:1-22
Tetanus vaccination is associated with differential DNA-methylation: Reduces the risk of asthma in adolescence - Janjanam, Vimala Devi, Mukherjee, Nandini, Lockett, Gabrielle A., Rezwan, Faisal I., Kurukulaaratchy, Ramesh, Mitchell, Frances, Zhang, Hongmei, Arshad, Hasan, Holloway, John and Karmaus, Wilfried Published:2016Publication:VaccineVolume:34, (51)Page Range:6493-6501doi:10.1016/j.vaccine.2016.10.068
Dietary variety and food group consumption in children consuming a cows' milk exclusion diet - Maslin, Kate, Dean, Tara, Arshad, Syed Hasan and Venter, Carina Published:2016Publication:Pediatric Allergy and ImmunologyVolume:27, (5)Page Range:471-477doi:10.1111/pai.12573PMID:27062104
DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis - Joubert, Bonnie R., Felix, Janine F., Yousefi, Paul, Bakulski, Kelly M., Just, Allan C., Breton, Carrie, Reese, Sarah E., Markunas, Christina A., Richmond, Rebecca C., Xu, Cheng-Jian, Küpers, Leanne K., Oh, Sam S., Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A., Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A., Duijts, Liesbeth, Sharp, Gemma C., Jankipersadsing, Soesma A., Nilsen, Roy M., Vaez, Ahmad, Fallin, M. Daniele, Hu, Donglei, Litonjua, Augusto A., Fuemmeler, Bernard F., Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M., Ren, Jie, Tost, Jörg, Gonzalez, Juan R., Peters, Marjolein J., Håberg, Siri E., Xu, Zongli, van Meurs, Joyce B., Gaunt, Tom R., Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P., Eng, Celeste, Baccarelli, Andrea A., Benjamin Neelon, Sara E., Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H., Wu, Michael C., Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W., Barcellos, Lisa F., Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W., Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M., Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K., DeMeo, Dawn L., Burchard, Esteban G., Ladd-Acosta, Christine, Snieder, Harold, Nystad, Wenche, Koppelman, Gerard H., Relton, Caroline L., Jaddoe, Vincent W.V., Wilcox, Allen, Melén, Erik and London, Stephanie J. Published:2016Publication:The American Journal of Human GeneticsVolume:98, (4)Page Range:680-696doi:10.1016/j.ajhg.2016.02.019
DNA methylation and genetic polymorphisms of the Leptin gene interact to influence lung function outcomes and asthma at 18 years of age - Mukherjee, Nadini, Lockett, Gabrielle A., Merid, Simon K., Melén, Eric, Pershagen, Göran, Holloway, John, Arshad, Syed Hasan, Ewart, Susan, Zhang, Hongmei and Karmaus, Wilfried Published:2016Publication:International Journal of Molecular Epidemiology and GeneticsVolume:7, (1)Page Range:1-17
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