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Specific targets of research include monocyte, macrophage, and Dendritic cell biology, particularly in terms of interactions with epithelial and stromal cells that are the targets of inflammation; pathways of T cell activation and differentiation in the context of chronic inflammatory diseases, particularly rheumatoid arthritis; and B cell dysregulation in lupus. Recent efforts have also focused on the impact of genetic variants of key immune response genes that shape the immune and inflammatory response. These efforts benefit from our close collaboration with the King’s College Programme in complex disease genetics. Our long term goal is to develop scientific knowledge as a basis to define better immune based therapies that relate to the pathogenesis of inflammatory disease, and that seek to restore immune homeostasis.
Molecular and Cellular Biology of Inflammation
DESCRIPTION
The mission of the Centre of Molecular and Cellular Biology of Inflammation is to be a basic science hub providing the rational basis to explore new avenues in the understanding, diagnosis and treatment of inflammation and its associated pathologies. It will achieve this by developing and exploiting cutting edge models and tools, both experimental and computational. Under study are a variety of animal systems (including humans, mice, and Drosophila) and experimental approaches (genetic, biochemical, immunological, molecular and imaging techniques). A major focus of the Centre is to investigate the function of individual cells and molecules in situ, in real time, within living tissues.Specific targets of research include monocyte, macrophage, and Dendritic cell biology, particularly in terms of interactions with epithelial and stromal cells that are the targets of inflammation; pathways of T cell activation and differentiation in the context of chronic inflammatory diseases, particularly rheumatoid arthritis; and B cell dysregulation in lupus. Recent efforts have also focused on the impact of genetic variants of key immune response genes that shape the immune and inflammatory response. These efforts benefit from our close collaboration with the King’s College Programme in complex disease genetics. Our long term goal is to develop scientific knowledge as a basis to define better immune based therapies that relate to the pathogenesis of inflammatory disease, and that seek to restore immune homeostasis.
Associated research programmes
Associated staff research interests
Interests:
The focus of our research is to understand at the molecular and cellular level pathways of T cell activation and differentiation that promote autoimmunity, and which contribute to the persistence of chronic immune and inflammatory responses. Specifically, we are interested in investigating the impact of altered T cell antigen receptor signalling (TCR) thresholds (both inherited and acquired) on (1) pathways of T helper cell activation, differentiation and cytokine gene expression, (2) pathways of cell migration, and (3) the mechanisms through which T lymphocytes regulate innate immune responses in vivo.
Tel:
020 7848 8631
Fax:
0207 848 8632
Email:
Website:
Interests:
Members of the Geissmann Lab (Development and Functions of Mononuclear Phagocytes) focus their efforts on understanding the molecular and cellular basis for the functional heterogeneity of the mononuclear phagocyte system in vivo. We have described the common precursor for macrophage, monocytes and dendritic cells (Fogg et al., Science 2006; Auffray et al., JEM 2009), discovered specialized population of monocytes (Geissmann et al., Immunity 2003, Auffray et al., Science 2007, Auffray et al., Annu. Rev. Immunol. 2009), and investigated the pathophysiology of diseases of this cellular system, including Langerhan’s cell histiocytosis (Senechal et al., Plos Meddicine 2007). To study the development and functions of phagocytes in vivo, in animal models and in man, we use fate mapping strategies and intravital imaging in mouse models in vivo, high-throughput or multiplex analysis of gene and protein expression ex-vivo from human cells purified by flow cytometry, and we develop new models for the study of the genetic control of phagocytes development and functions, such as the fruit fly Drosphila melanogaster. We plan to build on hypotheses and results generated using mouse and drosophila models to identify candidate genes responsible for human inflammatory diseases, to model and test (ex vivo) the functions of human monocytes and their roles in diseases, and - in collaboration with clinicians - to develop prospective cohorts to test biomarkers, diagnostic tools and therapeutic strategies.
Tel:
020 7848 6902
Fax:
0207 848 6743
Email:
Website:
Interests:
The Taams lab investigates regulation of the immune response in humans, during health and inflammation. Immune regulation is an essential process to prevent autoimmunity or chronic inflammation such as occurs in rheumatoid arthritis. We are particularly interested in the cross-talk between CD4+ T cell subsets and monocytes, and how this contributes to inflammation and regulation.
Part of our research focuses on a subset of CD4+ T lymphocytes with specialised immunosuppressive function. These so-called regulatory T cells (Tregs) have been previously shown to potently suppress adaptive immune responses. More recent work from our lab and others indicates that these Tregs also have distinct suppressive effects on innate immune cells, such as monocytes. Our current work is aimed at determining the molecular basis and the functional consequences of Treg-mediated monocyte modulation. We also investigate if and how inflammatory conditions alter Treg function, with a particular focus on activated monocytes.
A second research focus is on the role of Th17 cells during pathogenesis of rheumatoid arthritis (RA). Th17 cells are highly pro-inflammatory CD4+ T cells that are thought to contribute to inflammation and bone destruction in RA. Our aim is to define the molecular and cellular processes that drive IL-17 producing Th17 cells in RA, with a view to block this process. In addition, we are actively investigating if and how we can use Power Dopper Ultrasound to identify RA patients that have a more Th17-mediated, and therefore potentially more destructive, disease.
Part of our research focuses on a subset of CD4+ T lymphocytes with specialised immunosuppressive function. These so-called regulatory T cells (Tregs) have been previously shown to potently suppress adaptive immune responses. More recent work from our lab and others indicates that these Tregs also have distinct suppressive effects on innate immune cells, such as monocytes. Our current work is aimed at determining the molecular basis and the functional consequences of Treg-mediated monocyte modulation. We also investigate if and how inflammatory conditions alter Treg function, with a particular focus on activated monocytes.
A second research focus is on the role of Th17 cells during pathogenesis of rheumatoid arthritis (RA). Th17 cells are highly pro-inflammatory CD4+ T cells that are thought to contribute to inflammation and bone destruction in RA. Our aim is to define the molecular and cellular processes that drive IL-17 producing Th17 cells in RA, with a view to block this process. In addition, we are actively investigating if and how we can use Power Dopper Ultrasound to identify RA patients that have a more Th17-mediated, and therefore potentially more destructive, disease.
Tel:
020 7848 8633
Email:
Website:
Interests:
Signals from immune cells to other tissues are critical regulators of physiology and pathophysiology. Conversely, signals from non-immune tissues are often critical regulators of the immune response. However, these signals are poorly-understood biologically. The Dionne lab uses the fruit-fly Drosophila melanogaster to tease apart these interactions. The virtue of Drosophila for this kind of work is two-fold: its small size, quick generation time and extensively-annotated genome make it tractable via forward and reverse genetics and bioinformatic techniques, while its mechanisms of physiological regulation and the components of its immune system are recognizably closer to those of humans than those of other invertebrate model systems.
Our current focus is on the infection of Drosophila with Mycobacterium marinum. M marinum causes an invariably-lethal infection in Drosophila, with many similarities to human tuberculosis (Dionne et al., Infect Immun 2002; Dionne et al., Curr Biol 2006). We have previously described how this infection disrupts insulin signalling in the host, with resulting defects in anabolism that result in a cachexia-like condition. One current goal is to understand the mechanisms that generate this blockade to insulin signalling. As an outgrowth of this work, we are also investigating the mechanisms by which metabolic balance is ordinarily maintained. A second project in the lab is focussed on continuing our screen for host factors that regulate this infection; we have recently complemented the unbiased genetic approach with which we began with a more-targeted approach based on a bioinformatic survey of transcription-factor binding to genomic loci. A third project, in collaboration with the Geissmann laboratory, focuses on developing imaging techniques and genetic tools with which we can refine our understanding of the development and function of myeloid lineages in the fly.
Our longer-term goal is to develop a full understanding of the ways immune and non-immune tissues interact in healthy animals; how these interactions are altered by infection and inflammation; and how inflammatory responses are regulated. We hope to be able to translate our findings in the fly to mammalian models and ultimately to the clinical context.
Our current focus is on the infection of Drosophila with Mycobacterium marinum. M marinum causes an invariably-lethal infection in Drosophila, with many similarities to human tuberculosis (Dionne et al., Infect Immun 2002; Dionne et al., Curr Biol 2006). We have previously described how this infection disrupts insulin signalling in the host, with resulting defects in anabolism that result in a cachexia-like condition. One current goal is to understand the mechanisms that generate this blockade to insulin signalling. As an outgrowth of this work, we are also investigating the mechanisms by which metabolic balance is ordinarily maintained. A second project in the lab is focussed on continuing our screen for host factors that regulate this infection; we have recently complemented the unbiased genetic approach with which we began with a more-targeted approach based on a bioinformatic survey of transcription-factor binding to genomic loci. A third project, in collaboration with the Geissmann laboratory, focuses on developing imaging techniques and genetic tools with which we can refine our understanding of the development and function of myeloid lineages in the fly.
Our longer-term goal is to develop a full understanding of the ways immune and non-immune tissues interact in healthy animals; how these interactions are altered by infection and inflammation; and how inflammatory responses are regulated. We hope to be able to translate our findings in the fly to mammalian models and ultimately to the clinical context.
Tel:
020 7848 8635
Fax:
020 7848 6743
Email:
Website:
Interests:
Immuno-inflammatory mechanisms in rheumatoid arthritis.
Tel:
020 7188 5907
Fax:
020 7188 5883
Email:
Website:
CONTACTS FOR FURTHER INFORMATION
Professor Frederic Geissmann
Email
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