Th2 memory in allergic asthma and Tissue resident memory cells
Allergic asthma is a major health problem, which continues to rise in incidence and prevalence. Clinically, patients have intermittent and recurrent exacerbations of asthma associated with allergen exposure, ultimately leading to respiratory tract destruction. To investigate the relapsing, remitting character of clinical disease, we established several models of allergic asthma in mice. We discovered that mice recovered from an initial acute episode of allergic asthma harbour memory CD4 Th2 cells within lung infiltrates for their lifetime and that these cells respond rapidly to allergen during disease exacerbations. In a recent collaboration with Frank Brombacher at the University of Cape Town, we are also working on understanding memory responses to allergen in the context of Tuberculosis. Our efforts in the laboratory for this project are devoted to addressing the involvement of memory Th2 cells in the lung during allergic asthma. Despite current understanding of allergic disease, there are many details of the cellular and molecular pathways that remain unknown. We are using genomic technology to help elucidate and validate genes involved at critical points in the allergic response in lung.
Allergic disease is a chronic immune-mediated inflammatory disease with an enormous impact on health and well being and a high economic burden in Europe. The increasing incidence in the last decades is well documented and parallels the environmental changes of Industrialized countries. Although there appears to be a link between environmental factors and the high prevalence of allergic disease, the underlying mechanisms remain unclear. However, the environment may influence susceptibility to allergic disease through inherited epigenetic modifications of DNA. Environmental exposures such as diet, drugs, toxins and social environment seem to influence the risk of developing allergy in children. These exposures have been linked to methylation and acetylation of specific immune-related genes. Using a experimental model of allergic asthma, we investigate epigenetic changes in lung and immune cells to determine whether known epigenetic modifiers influence the susceptibility of allergic asthma in the offspring. The aim of this work is to gain insights on the interaction between the environment, epigenetic changes and susceptibility to allergic disease. These studies may have significant clinical implications on environmental exposure during pregnancy and ultimately may identify strategies to prevent allergic disease in high-risk children.
Ambrosia artemisiifolia L. (Asteraceae) called common ragweed is an annual Ambrosia herbaceous plant with origins in North America. Although it was first observed in Europe in the mid 19th century, it began to spread in Europe after 1940. It is a highly invasive plant with allergenic pollen that causes hay fever (rhino-conjunctivitis), asthma and atopic dermatitis. We are studying how environmental changes impact Ambrosia and how this, in turn impacts allergic disease as an approach to establish quantitative models of disease response as part of an overall strategy identify environmental stressors and disease risk.
GMOs, novel proteins and food allergy
The ability of a novel protein expressed in plants to induce allergy is a health concern. There are several important tests in use to test allergenicity of GMOs, but the role of experimental animals models in the safety evaluation remains unclear. As part of the GMSAFOOD project, we tested the alpha-amylase inhibitor peas, cowpeas and chickpeas created at CSIRO in Australia and Bt-maize (MON 810). We developed mouse models to test the ability of these particular GMOs to induce allergic responses to the transgenic proteins and to test their influence on existing allergic disease. Our main aim in this project is to develop models that closely mimic disease in humans and validate the predictability of these models to humans. These models are now applied to novel proteins such as insect proteins and to effects in the environment.
Regenerative medicine and biomaterials
The use of biomaterials in tissue regenerative medicine is on the rise. For many new biomaterials, the capacity to induce inflammatory and allergic responses against the implants is unknown. Working together with a large multidisciplinary team, we are testing the inflammatory and allergic potential of novel biomimetic materials for tissue healing and regeneration.