The research in my laboratory investigates how pathogen interaction with the innate immune system influences the development of adaptive immunity and inflammation. My particular interest is Type 2 inflammation, which is responsible for widespread suffering in allergy, as well as being a hallmark of infection with parasitic worms (helminths). Our work addresses some outstanding fundamental questions about the role of a specialised type of immune cell – the dendritic cell (DC) – in orchestration of Type 2 inflammation. DCs are centrally involved in initiation of immune responses in most settings, but the precise mechanisms by which they direct Type 2 inflammation are currently not known.
The main questions we are addressing at the moment are:
1) How do DCs become activated in Type 2 settings?
2) How necessary are DCs for induction and coordination of Type 2 inflammation?
3) By what mechanism do DCs initiate Type 2 inflammation?
Our research uses a combination of in vivo and in vitro model systems, focussing on the Type 2 response to the medically important helminth Schistosoma mansoni. Murine infection with this parasite provides a relevant experimental model of Type 2 inflammation that has been used extensively by my laboratory and others to reveal important cellular and molecular players and processes during hepatic, intestinal and pulmonary inflammation.
We have also begun to apply our understanding of immune mechanisms at play in helminth infection to pulmonary allergic inflammation, as well as to initiate studies using human DCs to complement and inform our murine work. Our expertise in isolation of delicate and rare cells from tissues, and multi-parameter flow cytometry, provides the opportunity to tackle the formidable technical challenge of clearly defining the activation and function of DCs and other immune cells during both murine and human pulmonary inflammation, where cell numbers are often extremely limited. Ongoing projects in this area include the investigation of mechanisms that control activation and renewal of airway macrophages and DCs, and mechanisms of cross-talk between pulmonary epithelial cells and DCs, during both murine and human Type 2 inflammation.
Our goal is to transform fundamental understanding of the cellular and molecular mechanisms by which Type 2 responses are initiated, maintained and regulated, to enable rational design of innovative therapies targeting cells or their products to combat Type 2 inflammatory disease.