Professsor of Gastroenterology
Innate Immunity in inflammation and Infection
Main Research Aims:
We are focused on defining innate immune pathways underpinning digestive disease and developing novel therapeutic approaches.
Current Research Themes:
Mechanisms of pattern recognition receptor function in health and inflammation
Pattern recognition receptors are families of ancient immune receptors conserved through evolution that recognize conserved molecular motifs present on microorganisms. Signaling through PRRs expressed in antigen presenting cells such as dendritic cells (DCs) dictates the nature of DC maturation and the phenotype of the ensuing adaptive immune response. This process is a central primary gatekeeper function of the immune response; correctly targeted signaling through PRRs results in timely clearance of infections and immune homeostasis. When dysregulated, aberrant innate signaling triggers inflammation. It is increasingly recognized the pathogenesis of many human diseases results from defects in innate sensing. The labs chief focus is on using large-scale molecular techniques in human cell systems to define how innate sensing occurs normally and how this breaks down in disease.
Molecular redefinition of human intestinal cells in health and digestive disease
We are utilizing single cell technologies to define intestinal subsets and characterize novel populations associated with gastrointestinal diseases including subsets of inflammatory bowel disease, GI cancer and infections of the gastrointestinal tract such as Salmonella. We utilize this information to characterize novel pathways driving immune pathology in these conditions and to inform in vivo studies defining the role of distinct subsets in immunity.
Improving the treatment and management of Inflammatory Bowel Disease
We have various drug and biomarker discovery programmes in IBD ongoing with the aim of defining subsets of patients amenable to novel therapeutic approaches. Members of the lab have identified compounds that modulate immune defects observed in IBD that are being functionally validated and tested in vivo for their utility in attenuating colitis. This work is supported by collaborations with various pharmaceutical companies and the US Harrington Discovery Institute.
Interferon-Gamma–Producing CD8+ Tissue Resident Memory T Cells Are a Targetable Hallmark of Immune Checkpoint Inhibitor–Colitis
Sasson SC. et al, (2021), Gastroenterology, 161, 1229 - 1244.e9
HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses
Buckley PR. et al, (2021)
IL-6 effector function of group 2 innate lymphoid cells (ILC2) is NOD2 dependent
Hardman CS. et al, (2021), Science Immunology, 6, eabe5084 - eabe5084
Multi-Modal Characterization of Monocytes in Idiopathic Pulmonary Fibrosis Reveals a Primed Type I Interferon Immune Phenotype
Fraser E. et al, (2021), Frontiers in Immunology, 12
Spatiotemporal analysis of human intestinal development at single-cell resolution
Fawkner-Corbett D. et al, (2021), Cell, 184, 810 - 826.e23