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Professor
Tim
Williams
Contact Details
National Heart & Lung Institute
Sir Alexander Fleming Building
South Kensington Campus
Imperial College London
London SW7 2AZ
Telephone
:
020 7594 3159 or 020 7594 3118
Email
:
tim.williams@imperial.ac.uk
Profile
The research of Leukocyte Biology is concerned with the role of different types of leukocytes in inflammatory reactions, particularly the mechanisms underlying the recruitment of leukocytes to tissues. There is a special interest in chemoattractants involved in the accumulation of effector leukocytes into the lung in allergic asthma. This interest led to the discovery of Eotaxin, a CC-chemokine that is produced at sites of allergic inflammation and has an important role in attracting eosinophils from blood microvessels in the airway wall. The Eotaxin receptor, CCR3, is highly expressed on eosinophils, and also on basophils, mast cells and a sub- population of Th2 lymphocytes. Two other Eotaxins, Eotaxin-2 and Eotaxin-3 have been described that also signal via CCR3. Current work is concerned with the functions of these receptors that are differentially expressed under different conditions. Sensitive bioassay systems using flow cytomentry ("GAFS"), have been established to measure the effects of chemoattractants on different leukocyte types. These systems have been employed to evaluate potential CCR3 antagonist molecules in purified or semi-purified leukocyte preparations or whole blood. The bioassay systems have also been used in the search for novel activities in extracts of inflamed tissues. Extracts of human nasal polyp tissue have been found to contain eosinophil-stimulating activity correspondiing to Eotaxin-1 and Eotaxin-2. The extracts also contained selective basophil-stimulating activity that unexpectedly corresponded with the presence of Insulin-like Growth Factors-1 and 2 (IGF-1 and IGF-2). Resent research is directed towards mechanisms underlying the population of tissues with mast cells, cells that circulate as progenitors and mature within the tissues. We have been investigating the chemoattractants involved in releasing mast cell progenitors from the bone marrow and mediating their recruitment to tissues. Progress has been made in identifying such chemoattractants, in murine and human systems using the same strategy employed in the discovery of Eotaxin.
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Last modified:
04 December 2009 11:38