'FROM DISCOVERY TO RECOVERY'
My previous research was to establish the exact role of LCs and dermal-derived DCs using genetically engineered mouse models. We recently engineered knock-in mice that express an enhanced green fluorescent protein (EGFP) under the control of the langerin (CD207) gene, a C-Type lectin expressed by LCs which enabled us to further characterize LCs, and directly study the dynamics of LCs both in vivo and ex vivo. A second knock-in was developed to specifically eliminate LCs in vivo by placing the human diphtheria toxin receptor under the control of the langerin gene. These transgenic lines will enable us to study the development and function of LCs during both steady-state conditions (tolerance) and in inflammatory contexts.
My research currently focuses on the role of pulmonary DC subsets in different models of lung inflammation. Recently a major DC population defined to be integrin aE-b7+CD207+CD11b- was found to be specifically localised at the basal lamina of the bronchial epithelia and arterioles of the lung, suggesting that they may be specifically involved in antigen capture and transport to mediastinal lymph nodes of the lung. Integrin aE-b7+ mediates adhesion of intraepithelial lymphocytes and DCs to E-cadherin, an epithelial specific cadherin involved in cell to cell adhesion. It is becoming increasingly clear that different DC subsets are involved in specialized roles and effector function. Together these observations suggest that pulmonary CD207+CD11b- DCs are key antigen-presenting cells of the lung capable of migrating across the airway epithelia for antigen sampling, transport and presentation to memory and/or effector cells in regional MLNs. Therefore, the LangEGFP and LangDTR models offer the unique possibility of addressing the role of CD207+ pulmonary DCs both during steady-state and inflammatory conditions, such as viral infection and experimentally induced asthma. The ability to track and specifically ablate these cells both in vivo and ex vivo may identify these lung DCs as the key proinflammatory cells necessary for Th1 and/or Th2 cell stimulation during airway inflammation.
Furthermore, to align myself with the immunology group within the CII, we are currently investigating the involvement of SOCS proteins in DC cytokine signalling and determining the impact of SOCS protein ablation on DC and T cell development and cell mediated immune responses, and their role in autoimmune disease (in collaboration with Prof Jim Johnston). I am also investigated the role of ARF6 (GTP binding protein) in T cell activation and anergy through the use of in vitro models and the development of an ARF6 conditional knockout model.
As part of the DEL All-Ireland Research Base grant I am also collaborating with key members of the CII to establish key in vivo models of respiratory and infectious disease. Four Home Office project licences have been written and are awaiting ethical approval to commence work with these models.
Since my appointment at QUB I have undertaken several external research activities, which reflect my expertise in my research domain, which are summarised below:
Invited Research Presentations
· MUGEN EU Network of Excellence, Athens (April 2006)
· BSI Immunology group, Edinburgh University (June 2006)
· DC-THERA EU Network of Excellence, Nijmegen (June 2006)
· National Institute of Immunology, New Dehli (November 2006)
· Nikolas Symposia on The Histiocytoses, Athens (June 2007)
· The British Society of Oral Maxillofacial Pathology, Belfast (May 2008)
· Roslin Institute, Edinburgh (September 2010)
· Max-Planck Institute for Infection Biology, Berlin (October 2009)
· Joint Meeting of the ISI/UIG Annual Conference, Belfast (September 2010)
· Royal Society of Microscopy, Belfast (July 2010)
· University of Otago, Dunedin (September 2011)
Established International Collaborations with Leading Researchers
· Prof Padraic Fallon (Trinity College Dublin)
· Prof Bernard Malissen (CIML, France)
· Prof Frederic Geissmann (King’s College, London)
· Dr Uwe Ritter (University of Regensburg, Germany)
· Dr Peter Hammerl (University of Salzburg, Austria)
External Peer Reviewer for the following Journals/Organisations
· Journal of Investigative Dermatology
· Trends in Immunology
· Health Research Board
· Consultant for Innate Pharma Biotech, France (Jan 2007 – Jun 2008)
· Expert Panel for Sanofi Pasteur MSD, France (April 2008)