Inflammation and Immunity Supervisors
Theme Leader: Professor Philip Ashton-Rickardt
Phillip Ashton-Rickardt
Inflammation and immunity
Memory T lymphocytes form the basis of immunological memory through their ability to rapidly eliminate invaders. We work on understanding the molecular basis of how memory T lymphocytes develop and how they are maintained. Our goal is to identify and characterise factors that protect memory cells from death and ensure their long-term survival through the activation of stem cell programmes for self-renewal.
We hope that the research proposed will lead to an improvement in vaccination through the induction of potent T cell memory and may provide a target for the elimination of auto-immune memory T cells.
Further Information
http://www1.imperial.ac.uk/medicine/people/p.ashton-rickardt/
Contact Details
p.ashton-rickardt@imperial.ac.uk
Tel: +44 (0)20 8383 8135
Marina Botto
Inflammatory diseases
Our research programme aims to understand the role of complement in health and disease. Over the years we have developed several in vivo experimental models which have helped to elucidate how complement contributes to the development of systemic autoimmunity (SLE) and renal inflammation. We have a longstanding interest in the molecular and genetic basis of SLE. A complementary research theme is to explore the consequences of complement dysregulation in vivo, specifically the relationship between uncontrolled complement activation and renal disease. These studies have opened the way to the design of safe and targeted complement inhibitor strategies.
Further Information
http://www1.imperial.ac.uk/medicine/people/m.botto/
Contact Details
m.botto@imperial.ac.uk
Tel: +44 (0)20 8383 2316
Glomerulonephritis
Research in the Renal Laboratory focuses on the causes and treatment of glomerulonephritis. We take a systems based approach, studying the disease pathway from genetic susceptibility, autoimmunity, inflammation and scarring, to the development of end stage kidney disease requiring dialysis or transplantation. We have a particular interest in rapidly progressive glomerulonephritis (RPGN), the two major causes of which are systemic vasculitis associated with anti-neutrophil cytoplasm antibodies (ANCA) and Goodpasture’s or anti-glomerular basement membrane (GBM) disease. We study pathogenic mechanisms and new approaches to treatment in rodent models of these diseases, including nephrotoxic nephritis, experimental autoimmune glomerulonephritis, and experimental autoimmune vasculitis. We use a full range of molecular, cellular and pathophysiological approaches and techniques. Our work has a strong translational focus, and we have a parallel programme of research into mechanisms and treatment in patients with glomerulonephritis. We are also investigating diabetic nephropathy, the progression of which shares mechanisms in common with that of those in glomerulonephritis.
Contact details
Tel: +44(0)20 8383 2308
Maggie Dallman
Immune regulation
Over-vigorous or inappropriate immune responses can lead to debilitating or life threatening conditions such as autoimmunity (e.g. diabetes, rheumatoid arthritis) and allergy. As our understanding of disease develops we find that dysregulated inflammatory responses are associated with conditions as diverse as alzheimer's disease and obesity. An understanding of and an ability to control inappropriate immunity and inflammation lie therefore on the path to successful treatment of these varied diseases. We are particularly interested in how endogenous signalling pathways (e.g. Notch, Hh) modify the response to inflammatory signals stimulated by exogenous (e.g. pathogens and fat) or endogenous (e.g. stress) stimuli. Our work explores these issues in a range of organisms from zebrafish to humans to study at the molecular, cellular and whole individual level not only the basis for disease but also potential approaches to therapy.
Further Information
http://www3.imperial.ac.uk/people/m.dallman
Contact Details
m.dallman@imperial.ac.uk
Tel: +44 (0)20 7594 5406
Dan Davis
Immune activation
Many of the key cell surface molecules involved in immune cell surveillance have been identified and an important new scientific frontier is to understand where and when each protein-protein interaction occurs to regulate cell functions. Thus, imaging has a major role to play in contemporary cell biology. We and others have found that immune cell communication is often accompanied by the segregation of proteins into submicrometer-scale domains at an intercellular contact or immunological synapse (IS). In addition, we found that immune cells can be connected by thin membrane tethers termed membrane nanotubes and it is possible that they represent a new mode of intercellular communication as well as having other important functional consequences, e.g. allowing HIV spread.
Further Information
http://www.dandavislab.co.uk/
http://www3.imperial.ac.uk/people/d.davis
Contact Details
d.davis@imperial.ac.uk
Tel: +44 (0)20 7594 5420
Richard Festenstein
Lymphocyte biology
Deciphering the epigenetic code in T cells
We work on fundamental aspects of gene regulation during T cell development. Our studies focus on a genetic model for epigenetic regulation. How individual cells make the decision to switch genes 'on' and 'off' during the development of specific cell types and how they 'remember' this decision through cell division is central to the biology of multi-cellular organisms. Our group studies factors that influence this decision and maintain it. We have shown that where a gene is located in the chromosome has a large effect on the probability of switching a given gene on or off. This phenomenon was first described in fruit flies and called position effect variegation (PEV). We have identified DNA sequences that can promote or overcome this silencing and shown that the extent of gene inactivation is dependent on the dosage of proteins implicated in DNA packaging. We are investigating the hypothesis that such effects may play a role in some human diseases and have recently shown that the triplet-repeats associated with several neurological diseases can silence genes in a similar manner to PEV and that chromatin modifiers are potential therapies.
Further Information
http://www.csc.mrc.ac.uk/Research/Groups/EPI/GeneControlMechanismsDisease/
Contact Details
r.festenstein@imperial.ac.uk
Tel: +44 (0)20 8383 8317
Guido Franzoso
Lymphocyte function and apoptosis
In addition to marshalling immune and inflammatory responses, NF-B transcription factors control cell survival. This control is crucial to T cell homeostasis, oncogenesis, and antagonism of TNF-R-induced killing. Previously we showed that the protective activity of NF-B involves a suppression of the JNK cascade and have identified several mediators of this suppression. Currently, we are seeking to determine how these mediators participate in the important functions that NF-B play in immunity, inflammation and cancer. In addition to gaining new insights into mechanisms of inflammation, autoimmunity and tumorigenesis, the studies have profound implications for developing new treatments for these diseases.
Further Information
http://www1.imperial.ac.uk/medicine/people/g.franzoso/
Contact Details
g.franzoso@imperial.ac.uk
Tel: +44 (0)20 8383 8421
T cell development
Our research focuses on T lymphocytes which protect from infection and some cancers. T cells can also cause autoimmune disease by damaging normal tissue. Predisposition to autoimmunity is strongly linked to HLA haplotype although the molecular bais of this poorly understood. The group is researching the mechanisms by which tolerance to self can breakdown in autoimmunity and novel approaches to restore self-tolerance. These challenges are being approached using disease models and genetic modification of T cells and haematopoietc stem cells to study the development of normal (Furmanski et al 2010 J Immunol 184:650) and autoimmune (Ferreira et al 2009 PNAS 106:8320) T cell repertoires.
Further information: http://www1.imperial.ac.uk/departmentofmedicine/divisions/immunologyandinflammation/immunology/dyson/
Contact Details
peter.dyson@imperial.ac.uk
Tel: +44 (0)20 8383 8252
T Cell Motility
The regulation of memory T lymphocyte trafficking is the main focus of my research. We have established unique in vivo models of T lymphocyte trafficking to analyse the physiological relevance of the observations made in vitro in the human system. Our major contributions have been in the field of antigen-dependent recruitment, which allows selective recruitment of primed T cells to localise antigenic sites, and have unveiled key molecular mechanisms of this effect, which can be targeted pharmacologically. Some of these findings have been patented through IC Innovations.
The long-term plan of my research is to provide translational bridges between T cell homing mechanisms and therapy of chronic human immune-mediated diseases, including transplantation and autoimmunity.
In addition, based on preliminary observations we are testing innovative vaccination strategies (organ-specific vaccination) aimed to achieve organ-selective memory T cell trafficking and amplifying the potential of adaptive T cell memory in HIV infection and gut infestations, which is highly relevant to worldwide infectious diseases. We are currently developing these studies with an aim to provide a solid basis for imminent translational outcome.
Further information: http://www1.imperial.ac.uk/medicine/people/f.marelli/
Contact Details
f.marelli@imperial.ac.uk
Tel: +44 (0)20 8383 1704
Allergy and Clinical Immunology
Allergen injection immunotherapy involves the repeated administration of allergen extracts to IgE-sensitised allergic individuals in order to induce longlasting clinical and immunological tolerance. We have shown that in hayfever immunotherapy acts by suppression of allergic inflammation and generation of ‘protective’ IgG antibodies as a consequence of the induction of regulatory T cell responses. We are now testing whether the sublingual route may also induce tolerance and exploring the underlying modulation of antigen-specific T cell and B cell responses in the periphery and in the nasal mucosa. These studies have informed the development of novel therapies and biomarkers that may predict the clinical response to treatment.
Further information
http://www1.imperial.ac.uk/nhli/respiratory/allergy/
http://www1.imperial.ac.uk/medicine/people/s.durham/publications
Contact Details
Tel +44 207 351 8024
Lymphocyte Development
We are interested in cell commitment and gene regulation during development. We use lymphocytes and other cell types as models to study how gene expression patterns are transmitted through cell division, and to explore the molecular basis of lineage choice. Currently, the core research activities of the group include inter-related studies on (i) Ikaros family transcription factors (ii) cohesin function in gene expression and genome organization (iii) REST and Polycomb repressor complexes in stem cells (iv) Pluripotency and reprogramming and (v) RNA interference, Dicer and small non coding RNAs.
Further information
http://www.csc.mrc.ac.uk/Research/Groups/EPI/LymphocyteDevelopment/
Contact Details
matthias.merkenschlager@imperial.ac.uk
Tel: +44(0)20 8383 8239
