I have always been interested in the immune system. Allergic diseases and the immune response are particularly fascinating to me.
In allergic diseases, the immune system responds to things that it shouldn't, like dust or an allergen from a pet. While everyone is exposed to these substances in our homes or workplaces, not everyone is allergic. Determining why some people are allergic and others are not was the hook that got me interested in this field.
In my lab, we are working on determining what causes the development of severe allergic asthma as opposed to mild or moderate forms of the disease, which are more amenable to therapeutic interventions. We are focused on establishing how exposure in early life (including in utero) influences allergic asthma development.
Notably, we have demonstrated that the production of additional factors associated with severe allergic asthma synergizes with factors produced in mild/moderate disease.
Using a mouse model of allergic asthma in which one strain develops a phenotype characteristic of mild asthma (C3H/HeJ) and others develop a phenotype characteristic of severe disease (A/J), we have identified several novel mechanisms through which asthma severity is regulated.
The National Institutes of Health has continuously funded my research since 2012.
Increased nasal epithelial cell responsiveness to IL-17A in paediatric asthmatics with low blood neutrophil count, low traffic-related air pollution exposure and good asthma control. Clinical and Experimental Allergy. 2022; 52:569-573.
Age and early maternal smoking contribute to epithelial cell IL-13 responsiveness in a pediatric asthma population. Allergy: European Journal of Allergy and Clinical Immunology. 2019; 74:2485-2487.
Combined administration of anti-IL-13 and anti-IL-17A at individually sub-therapeutic doses limits asthma-like symptoms in a mouse model of Th2/Th17 high asthma. Clinical and Experimental Allergy. 2019; 49:317-330.
Maternal house dust mite exposure during pregnancy enhances severity of house dust mite-induced asthma in murine offspring. Journal of Allergy and Clinical Immunology. 2017; 140:1404-1415.e9.
IL-17A enhances IL-13 activity by enhancing IL-13-induced signal transducer and activator of transcription 6 activation. Journal of Allergy and Clinical Immunology. 2017; 139:462-471.e14.
Differential control of CD4(+) T-cell subsets by the PD-1/PD-L1 axis in a mouse model of allergic asthma. European Journal of Immunology. 2015; 45:1019-1029.
PD-L2 modulates asthma severity by directly decreasing dendritic cell IL-12 production. Mucosal Immunology. 2013; 6:728-739.
Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nature Immunology. 2010; 11:928-935.
CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. The Journal of Experimental Medicine. 2005; 202:1549-1561.
Delayed Microbial Maturation Durably Exacerbates Th17-driven Asthma in Mice. American Journal of Respiratory Cell and Molecular Biology. 2023; 68:498-510.