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Translational Immunology, Inflammation and Infection

Leaders: Professor Joseph Keane, Professor Aideen Long and Professor Mark Little.

Within TTMI there are over 30 basic and clinician PI’s active within translational immunology, inflammation and infectious diseases. Immunology research transcends the translational spectrum of integrating basic mechanistic immunological studies with specific clinical disease focus investigations. Current areas of research include molecular and cellular immunology (including human and animal models of differentiation, cytokine secretion and effector function), immunogenetics, leukocyte migration and nanomedicine. These studies are all translational in nature and focus on inflammatory diseases such as eczema, inflammatory bowel disease (IBD), coeliac disease, stroke, vasculitis and sepsis. The infectious diseases addressed include tuberculosis, HIV and Hepatitis C. PI’s also actively collaborate with many other Schools in TCD, such as immunologists in TBSI, where Professor Fallon and Professor Little also have laboratories.

These PIs have an outstanding track record in grant funding, for example in 2010-11 TTMI Translational Immunology PI’s were awarded €10.3 million in research grants. The work is funded by multiple agencies (exchequer and non-exchequer, National and International). For example, Researchers in TTMI are in receipt of multiple Science Foundation Ireland (SFI; including 3 x Principal Investigators, 1 x Stokes Chair, 1 x SIRGs and two President of Ireland Young Investigator Awards). PI’s working in the area of translational immunology, inflammation and infection publish in a broad range of high impact journals, such as Immunity, Nature, Science, Nature Medicine, Nature Genetics, New England Journal of Medicine, Nature Immunology.

Current Research Activity

The tuberculosis (TB) immunology group led by Professor Joseph Keane is dedicated to improving our understanding of TB immunobiology; with a view to generating better tuberculosis tests, treatments and vaccines. The group is currently dedicated to models of tuberculosis that are informed by transcriptomics and systems biology. Dr. Ronan O’Toole also works on the genetics of TB.

Professor Aideen Long’s group focuses on the study of the Protein Kinase C (PKC) family of enzymes and their role in T lymphocyte function, including migration and cytokine secretion. Working with Professor Suzanne Norris they study mechanisms used by the Hepatitis C virus to manipulate PKC activity resulting in subversion of the immune system and unresponsiveness to interferon-alpha therapy.

Professor Padraic Fallon’s research team is working to elucidate underlying mechanisms of aberrant immune function and develop novel therapeutic strategies for inflammatory diseases. The main diseases addressed are allergic lung inflammation (asthma), skin inflammation (eczema) and inflammatory bowel disease (ulcerative colitis and Crohn’s disease). This research involves the translational spectrum from samples from patients to the use of animal models. Together with Professor Alan Irvine, this group has identified a mouse model with mutations in the filaggrin gene as the major cause of eczema in humans.

Professor Ross McManus is a Senior Lecturer in Molecular medicine and has research interests in human population genetics particularly focusing on inflammatory diseases such as coeliac disease, psoriasis and related diseases, and IBD. Professor Tom Ryan’s group also studies genomics in the context of disease, and works with Professor McManus, particularly focusing on sepsis and the regulation of proinflammatory/regulatory cytokines in these patients.

Dr. Pat Walsh is based in IMM and National Children’s Research Centre and is a T cell immunologists addressing T cell function in IBD, arthritis and psoriasis. Dr. Sarah Doyle research is on innate cell signalling in children and the elderly, with laboratories based in National Children’s Research Centre and IMM.

Professor Yuri Volkov leads the Nanomedicine and Molecular Imaging team at the IMM, focusing on the mechanisms through which nanoparticles/materials interact with human cells in the context of cancer and inflammation. This group has recently established a clear link between autoimmune diseases such as rheumatoid arthritis and nanoparticles.

The group of Dr. Derek Doherty works in the area of human cellular immunology and are interested in the mechanisms by which cells of the innate immune system control adaptive immune responses and how they can be exploited for the design of improved vaccines and therapies. Working with Professors Colm Bergin, Suzanne Norris, and John Reynolds they are currently investigating how human natural killer cells, natural killer T cells and γδ T cells influence the functions of dendritic cells, B cells and conventional T cells and how they contribute to immunity against hepatitis B, C and HIV and the pathogenesis of autoimmune disease, obesity and cancer.

Professor Tom Rogers is Clinical Professor of Microbiology with an interested in hospital acquired infection including Clostridium difficile and Aspergillius fumigatus. Professor Philip Murphy, Tallaght Hospital, has collaborations with TTMI scientists on Aspergillius fumigatus infections of patients. Also in SPD, Dr. Stephen Smith is investigating antibiotic resistance and virulence in gram-negative bacteria (E.coli) and isolates of Pseudomonas aeruginosa from cystic fibrosis patients. Dr. Henry Windle’s research focuses on the molecular mechanisms of Helicobacter pylori infection and the design of vaccine strategies to protect against infection and associated pathologies.

Dr. Ronan Mullan is Consultant Rheumatologist and Clinical Senior Lecturer in Tallaght Hospital. His research interests include the molecular mechanisms of synovial inflammation in Rheumatoid Arthritis, and common inflammatory mechanisms of systemic autoimmune disease, metabolic syndrome and ageing. His current translational research project is investigating the interplay between cellular glucose metabolism and inflammation in Rheumatoid Arthritis.

Dr Gareth Brady is the Ussher Assistant Professor of Vascular Biology and heads the Translational Inflammation Research Group which focuses on the study of human-adapted poxviruses as a tool to understand the molecular basis of innate immune signalling and inflammation. Through an understanding of how these viruses inhibit inflammation, Dr Brady aims to develop novel anti-inflammatory therapeutics with potential applications in the treatment of autoimmune vasculitis and other inflammatory diseases.

Professor James O’Donnell and Dr. Roger Preston have on-going basic scientific research program focuses on several different areas within the field of vascular biology [1] The role of the protein C pathway in this context. [2] Von Willebrand disease (VWD), and role in the pathogenesis of Plasmodium falciparum cerebral malaria. [3] The National Centre for Hereditary Coagulation Disorders at St James's Hospital (NCHCD) functions as a tertiary referral centre for Irish patients with bleeding or thrombotic disorders, and is amongst the largest centres in Europe. The co-localisation of this clinical facility, together with our large basic scientific Haemostasis Research group in the IMM, provides a unique opportunity to develop an international centre of excellence over the next five years to perform excellent translational research. For example, we have a North-South collaborative study identify causative mutations in Irish patients with haemophilia and VWD (Senior author – Dr. Vince Jenkins.

The above outstanding PI’s in immunology research is reinforced by core technologies in TTMI (flow cytometry facility, Category 3 laboratory, high content analysis, next generation sequencing and Bioresources). This excellence in people and infrastructure combined with access to patient samples in the adjacent hospitals establish in TTMI an international focus of translational immunology, inflammation and infection.

Featured TTMI Researchers