Project: Understanding the causes of immune paralysis and lethal secondary infections in sepsis and trauma patients
Villadangos Group
Severe infections (sepsis) and trauma cause dangerous "cytokine storms" followed by a period of immunosuppression that can last for several weeks. Immunosuppressed patients are at risk of suffering secondary or opportunistic infections, a major cause of death in intensive care units. Indeed, secondary pneumonia is a major contributor to morbidity and mortality during viral pandemics (Influenza, COVID-19). Our laboratory has discovered that impairment of macrophages and dendritic cells, the primary initiators of T cell immunity, plays a critical role in immunosuppression. We have termed this phenomenon "immune paralysis".
The goal of this project is to characterise the mechanisms that cause macrophage and dendritic cell paralysis and to develop therapies to prevent immunosuppression and secondary infections.
Further reading:
A Roquilly, … and J. A. Villadangos. 2017. Local modulation of antigen presenting cell development after resolution of pneumonia induces long-term susceptibility to secondary infections. Immunity 47:135-147. PMID: 28723546.
A Roquilly… and JA Villadangos. 2020. Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis. Nat Immunol 21:636-48. PMID 32581370.
A Roquilly, JD Mintern and JA Villadangos. (2022). Spatiotemporal adaptations of macrophage and dendritic cell development and function. Annu Rev Immunol 40:525-57, PMID: 35130030.
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Villadangos Group
6 vacancies
The Villadangos group studies the first event that triggers adaptive immune responses: the presentation of pathogen or tumour antigens to T cells by Dendritic Cells, B cells and Macrophages. We are characterizing the development, regulation and impairment of antigen presenting cells by pathogens, inflammatory mediators and tumours. We are also dissecting the biochemical machinery involved in antigen capture, processing, and presentation. We use this knowledge to understand how T cell-dependent immunity is initiated and maintained and apply it to design better vaccines and immunotherapies against infectious agents and cancer.
All our projects are open to Honours/Master of Biomedical Science students and PhD/MPhil graduate researchers
Villadangos Group Current Projects
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Improving the formation of protective immunity against human viruses
PhD/MPhil, Master of Biomedical Science, Honours
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Understanding the causes of immune paralysis and lethal secondary infections in sepsis and trauma patients
PhD/MPhil, Master of Biomedical Science, Honours
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Investigating the role of dendritic cell O-GlcNAcylation in adipose tissue homeostasis and immune function
PhD/MPhil, Master of Biomedical Science, Honours
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Harnessing the power of RNA technology for vaccines and therapeutics
PhD/MPhil, Master of Biomedical Science, Honours
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Regulation of Complement by Membrane Receptor Ubiquitination
PhD/MPhil, Master of Biomedical Science, Honours
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A novel link between metabolism and immune function: O-GlcNAc glycosylation
PhD/MPhil, Master of Biomedical Science, Honours
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Trogocytosis: a novel communication system between cells of the immune system
PhD/MPhil, Master of Biomedical Science, Honours
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MR1 – a molecular alarm system for bacterial infection
PhD/MPhil, Master of Biomedical Science, Honours
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Regulating macrophage 'eating' for cancer and pathogen control
PhD/MPhil, Master of Biomedical Science, Honours
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The immune signature of sepsis
PhD/MPhil, Master of Biomedical Science, Honours