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Centre for Allergy Research (C.A.R.) Department of Pharmacology |
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Allergy Research Groups and
Summary of their Work Prof John
Foreman. Professor of Immunopharmacology, Dean of Students. Tel: 0207
679 4545 or 7314, e-mail: john.foreman@ucl.ac.uk Mr Thomas Clark Mr Nick Hayes The Group has two main research projects in progress: 1. The mechanism of hyperreactvity of the human nasal airway. We are using platelet-activating factor-induced hyperreactivity in normal volunteers as a model and are comparing this with hyperreactivity in patients with allergic rhinitis. We are exploring the roles of kinins and eosinophils in the hyperreactivity. 2. The role of histamine H3 receptors in the control of nasal airway function. |
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Prof. Fred L. Pearce (Professor of Biological Chemistry, Department of Chemistry; UCL; Deputy Dean of Students, UCL); Dean of the Faculty of Mathematical and Physical Sciences UCL); tel: +44 (0)20 7679 7235; email: f.l.pearce@ucl.ac.uk Hon. Research Fellows: Dr. El-Sayed K Assem Dr. Beatrice Y Wan Dr.K H Peh Miss Arna Alic Research interests in: Mast cells, allergy, histamine, asthma and anti- allergic drugs. Our research focuses on studies on chemical mediators of acute allergic reactions. To understand more fully the nature of acute allergic reactions we are currently studying in detail the mechanism of histamine release from mast cells of various species, comparing the pharmacological properties of mast cells from different tissues and examining the mode of action of modern anti-allergic drugs in these test systems. To this end, we have developed methods for the isolation of intact mast cells from human, lung, skin, intestine, stomach, bladder, prostate and uterus. We are examining the roles of these cells in different disease states, their ability to produce new chemical agents that may orchestrate inflammatory responses, the changes that the cells may undergo in the course of active disease, and the detailed biochemical events involved in their activation. To the latter end we are determining the role of ion currents and the activation of specific pro-enzymes. Identification of these mechanisms may provide novel targets for the modulation of mast cell function. Professor Santa Jeremy Ono,
GlaxoSmithKline Professor of the Biomedical Sciences, Chair, Department of
Immunology, Institute of Ophthalmology; Professor, Institute of Child Health,
University College London Mr. David Kai-yin Chau Dr. Veronica Cheung-Chau Miss Rachel Ajao Dr. Takao Nakamura Dr. Masko Toda Mr. Michael Radosevich Mr. Alex Nugent This
laboratory investigates the cell and molecular biology of allergic
inflammation and the genetics of atopy.
Studies on the cell biology of allergic disease make use of animal
models of allergic conjunctivitis, where serial analyses of gene expression
and proteomics are used to identify gene products involved in the acute and
late phase reactions. Presently,
we are most interested in the roles individual chemokines play in acute
disease as well as in mast cell development and signal transduction. In the area of genomics, we have
focused on genetic polymorphisms that may explain susceptibility to atopic
diseases, with special attention on variation between atopic diseases. Finally, we also study transcription
factors that may allow us to skew the T helper response in allergic disease. Dr Anna Koffer. Physiology Department, UCL; Rockefeller Building, University Street London WC1E 6JJ; e-mail: a.koffer@ucl.ac.uk ; +44 171 209 6094 (tel); +44 171 387 6368 (fax) The
work of this Group has identified small Rho-related GTPases as regulators of
both secretion and actin cytoskeleton in mast cells. Although strongly
correlated, signalling pathways from these GTPases to the downstream
effectors that activate secretion and the cytoskeleton appear to be divergent.
Our next aim is to explore the shared and distinct signals that induce
motile, secretory and endocytotic responses. We are investigating the
distribution of cytoskeletal components and their relationship to exocytosis
and endocytosis in mast cells responding to stimuli applied under gradient,
as compared to non-gradient conditions. Cells are monitored by microscopy and
analysed using sophisticated software for deconvolution and/or image analysis
in order to relate these cellular functions, both temporally and spatially.
Permeabilised cells and the re-constitution and/or depletion approach are
used to investigate functions of specific proteins (particularly the
actin-binding proteins that are regulated by phospholipids). Dr EL-Sayed K Assem. Emeritus Reader in Immunopharmcology, Dept of
Pharmacology, UCL; Hon Consultant Physician, UCL Hospitals; Hon Research
Fellow, Dept of Chemistry, UCL. Tel 020 7679 3759, Fax 020 7679 380 7298,
e-mail; e.assem@ucl.ac.uk 1. Drug-induced disease. Allergic reactions to drugs, including mechanism, in vitro tests for detection and prediction; direct involvement of the heart (disturbance in rate, rhythm, force of contraction and coronary flow) and kidney ("ischaemia" and protein leakage); life-threatening reactions to anaesthetic drugs, which are mainly due to neuromuscular blocking drugs (NMB) and predominantly affect women !. The main epitope is the quaternary ammonium group, which is also found in many other compounds, e.g. antiseptics, cosmetics and within the body. 2. Experimental models of asthma and inflammatory bowel disease. These models are used to study the mechanism of the disease process and of drug action (e.g. sulphasalazine and balsalazide), and novel approaches to treatment. 3. Inhibitory effects cyclosporin-A and its
analogues, and tacrolimus on the activation of mast cells and basophils, and
the signal transduction mechanism. 2. 4.
Role of nitric oxide and hydrogen peroxide in the activation of mast cells and
basophil leucocytes. 3. 5.
K+ channels involved in the activation of mast cells. 4. 6.
Adenosine receptor subtypes involved in the modulation of airway smooth
muscle activity. Dr. Glenis Scadding. Consultant Physician,
Royal National Throat Nose & Ear Hospital, Grey's Inn Road, London WC1X
8DA; e-mail: g.scadding@ucl.ac.uk Dr. Virginia Calder. Institute of
Ophthalmology University College London, 11-43 Bath Street, London EC1V 9EL;
Tel 0207 608 6876, Fax 44- 0207 608 6810; e-mail: v.calder@ucl.ac.uk Research interest: The role of T lymphocytes in chronic allergic eye disease: Chronic allergic eye disease includes a range of
disorders from the relatively mild giant papillary conjunctivitis (GPC), to
the more severe forms of vernal keratoconjunctivitis (VKC) and atopic
keratoconjunctivitis (AKC). Both VKC and AKC can be sight-threatening due to
effects on the cornea. In all three clinically distinct forms, activated
CD4-T cells and eosinophils are the main cell types which infiltrate the
conjunctiva. There is also macrophage activation, enhanced class II
expression and collagen deposition due to fibroblast activation within the
conjunctiva. To understand the role of the infiltrating T cells, T-cell lines
have been established from conjunctival biopsies, and their cytokine profiles
determined by ELISA, intracellular cytokine staining and RT-PCR. Results
suggest that in more chronic disease (AKC), the T cells produce mainly
IFN-gamma whereas in VKC, IL-5 and IL-13 predominate. Topical cyclosporin A
is an effective therapy in both VKC and AKC, confirming the importance of T
cells in these forms of disease. We are currently investigating the
antigen/allergen specificities of the T cells, the ability to modulate the T
cell cytokine patterns in vitro and the immune function of conjunctival
epithelial cells, including their ability to support T cell responses. Dr Robin McAnulty, The Centre for
Cardiopulmonary Biochemistry and Respiratory Medicine at UCL (Director Prof
Geoffrey Laurent) Mast cells and
fibroblasts have both been localised to peri-bronchial fibrotic lesions of
airways from asthmatic patients and in lungs of patients with fibrosis. A
variety of mediators released from activated mast cells have been shown to
induce fibroblast proliferation. One such mediator is a 134kD serine
protease, tryptase. The mechanism by which tryptase causes fibroblast
proliferation is unclear. Recent evidence suggests that tryptase can activate
a 7 loop transmembrane, G-protein coupled receptor, PAR-2. We have
established that 1. Tryptase causes proliferation of fibroblast cell lines
isolated from human lung parenchyma and airways, which is dependent upon its
catalytic activity. 2. Selective activation of PAR-2 causes fibroblast
proliferation. 3. PAR-2 is localised to the cell surface of both human lung
parenchymal and airway fibroblasts. Future work will establish the role of
PAR-2 in extracellular matrix production by fibroblasts and the localisation
of PAR-2 in human airway biopsy samples using immunohistochemistry. Dr Ian Akers Dr. Alan Jaques, Prof. Tom Rademacher's Lab
(Molecular Pathology), UCL, Windeyer Building This project involves
the study of glyco-phospholipids, the enzyme(s) which cleave them from their
precursors, and the role of these molecules in allergies. These molecules
have been implicated in the release of allergic mediators from mast cells
following IgE cross-linking. My goal is to determine: (a) how these molecules
are produced and secreted by cells, (b) where in the signal cascade these
molecules might fit, (c) whether their production or function can be blocked.
Dr. Helen Whitby -Latham (present address Imperial
College, London. Tel: 020 7504 9228) Professor Graham A. W. Rook. Department of Bacteriology, UCL,
Windeyer Building; e-mail: g.rook@ucl.ac.uk Research interest: Infections and immuno-endocrine interactions. Dr Jonathan Powell, Unilever; e-mail: jonathan.powell@unilever.com We are interested in
possible impacts of dietary micronutrients (particularly antioxidants, PUFAs
and phytosterols) upon the course of Age related degenerative diseases. We
have seen consistent affects of Dr Ian Kimber. Zeneca, Immunology Dept,
Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ;
Tel 01625 515408, Fax 01625 590249; e-mail: ian.kimber@ctl.zeneca.com The interests of the Group are focused on the molecular mechanisms through which chemicals and proteins induce allergic disease. Our primary interests are: (a) The induction phase of skin sensitization, epidermal cytokines and the induction and regulation of Langerhans cells migration and maturation.(b) The regulation of cytokine expression by human dendritic cells. (c) The development and function of subpopulations of CD4 and CD8 T lymphocytes and their roles in the induction and elicitation of chemical and protein allergy. (d) The roles played by cytokines in the selective development of Th1 and Th2, and of Tc1 and Tc2 cells. (e) Food allergy and the processing of protein allergens by antigen-presenting cells. |
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Last revised: January 14, 2000October 01 |
