Supervisor View Full DetailsOctober 11, 2016
Fellowship Call for 2019October 12, 2018
Full NameDr Selinda Orr
Department:School of Medicine, Dentistry and Biomedical Sciences
Organisation:Queen's University Belfast
- infectious disease and the immune system
- Infectious diseases
The research in my lab is focused on understanding how the immune system responds to different fungal pathogens including Candida and Aspergillus with the aim of 1) identifying ways to manipulate the immune response to improve patient outcome or 2) to identify factors to stratify patient groups into high or low risk of developing life threatening invasive fungal infections. We recently generated a number of novel models to examine the collective role of various pathogen recognition receptors (PRRs). We are investigating how the receptors function individually, where/when they are redundant, where/when/how they collaborate to induce a robust immune response. In addition we are comparing the immune response to different fungal spp. with varying pathogenicities. This information is required in order to develop novel vaccine and immunotherapy approaches. We are also examining polymorphisms in PRRs and immune response to Aspergillus in “at risk” patient groups in order to identify factors which could be used to stratify these “at risk” patients into low and high risk patients for developing invasive aspergillosis. This would allow targeted prophylactic therapies for the high risk patients.
Invasive fungal infections including Candida-induced sepsis are a major healthcare problem, resulting in 1.5 million deaths per year. Delays in diagnosis, problems identifying the responsible pathogen and inadequate treatments contribute to unacceptably high mortality rates for these patients. While hyphal-forming C. albicans is a major cause of these infections, there has been a shift towards increased predominance of non-hyphal-forming spp. including C. parapsilosis, and the drug resistant C. glabrata and C. auris spp. Pathogen recognition receptors differentially recognise and respond to yeast versus hyphal Candida formats. Additionally, we recently showed that non-hyphal forming Candida spp. induce IL-27 production, which limits anti-fungal T cell responses thereby prolonging infection in mice, while hyphal-forming Candida spp. actively block IL-27 production. New diagnostics or infection profiles associated with hyphal/non-hyphal Candida infections, novel treatments and a better understanding of the immune response to hyphal- versus non-hyphal-forming Candida spp. are required to improve the high mortality rates.
We plan to address these knowledge gaps through three aims: We will 1) mechanistically characterise hyphal versus non-hyphal host immune responses; 2) determine the effect of modulating the host response to non-hyphal forming Candida spp. during invasive infections; and 3) identify hyphal versus non-hyphal Candida infection signatures in sepsis patients. This project will identify Candida-specific infection signatures and mechanistically characterise and test the therapeutic potential of modulating Candida-specific pathways or responses to address a currently unmet medical need that requires urgent attention.