ISTM

My interests are in inflammatory diseases, mainly rheumatoid arthritis:

• What is the function of chemokine presenting and transporting molecules in the endothelium, leading to leukocyte migration into the inflamed tissue?
• What are the chemokine receptors on leukocytes that mediate their migration?
• Can stem cells be used as anti-inflammatory therapy?
• Can stem cells be targeted to inflamed tissues by using chemokine receptors?

My group is based in laboratories at the Robert Jones & Agnes Hunt Orthopaedic Hopital at Oswestry. It uses a variety of techniques: cell culture, flow cytometry, chemotaxis assays, immunohistochemistry, confocal microscopy, RT-PCR, western blots.

In 2010 I moved to Bristol University and retain a visiting honorary role at Keele University from 1 October 2010 to 30 September 2013.

For further details please see: Prof Middleton's page at the University of Bristol

ISTM Research theme: 1. Infection, Inflamation & Immunity
                                    2. Bioengineering & Therapeutics

We are interested in the mechanism of leukocyte emigration from the blood and into tissues at sites of inflammation, with focus on rheumatoid arthritis. The involvement of chemokines and their receptors/binding sites are being examined.

We are currently studying the expression of chemokine binding sites on the endothelium that may be involved in transcytosing chemokines and presenting them to blood leukocytes. These sites include glycosaminoglycans and the Duffy receptor and their functional contribution is beginning to be addressed.

Another project is studying the expression of chemokine receptors on leukocytes in rheumatoid arthritis with the aim of revealing therapeutic targets in the disease. This has been by using a functional genomic and protein expression approach. Selective expression of chemokine receptors on leukocytes in the rheumatoid synovium has been found, which may cause the recruitment of specific leukocyte subsets into the diseased tissue.

Funding for our work is from the Arthritis Research Campaign, Smith’s Charity, Wellcome Trust, BBSRC and Astrazeneca.

Selection of publications:

Middleton, J., Neil, S., Wintle, J., Clark-Lewis, I., Moore, H., Lam, C., Auer, M., Hub, E.and Rot, A. (1997). Transcytosis and surface presentation of IL-8 by venular endothelial cells. Cell 91(3): 385-395.

Patterson, A.M., Siddall, H., Chamberlain, G., Gardner, L. and Middleton, J. (2002). Expression of the duffy antigen/receptor for chemokines (DARC) by the inflamed synovial endothelium. Journal of Pathology 197(1): 108-116.

Patterson, A.M., Schmutz, C., Davis, S., Gardner, L., Ashton, B.A. and Middleton, J. (2002). Differential binding of chemokines to macrophages and neutrophils in the human inflamed synovium. Arthritis Research 4(3): 209-214.

Middleton, J., Patterson, A.M., Gardner, L., Schmutz, C. and Ashton, B.A. (2002). Leukocyte extravasation: chemokine transport and presentation by the endothelium. Blood 100(12): 3853-3860.