Dr Philip F Watson PhD

Senior Lecturer


Academic Unit of Endocrinology and Reproduction
E Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX

Room EU05

Telephone: +44 (0)114 215 9228
Email: p.f.watson@sheffield.ac.uk

Biography

I was awarded my PhD in 1990 from the University of Sheffield, after which I was awarded the John Stokes Research Fellowship and worked for 2 years in the Department of Pharmacology, studying genetic mechanisms of resistance to antifungals. In 1991 I was appointed as Lecturer in the School of Medicine, and Senior Lecturer in 1994. I am currently based in the Department of Human Metabolism.

Research Interests

My main research interests center on the aetiology of endocrine autoimmune disease, with a particular focus on the thyroid. Autoimmune thyroid disease is the most prevalent form of organ-specific autoimmunity in the population and affects approximately 1-2% of individuals. Antigenic targets in autoimmune thyroid disease are well characterised and this, together with the availability of patient material, makes the disease and important model for other forms of autoimmunity. In seeking to better understand the origins of thyroid autoimmunity we have developed techniques to study the nature of the immune response. In particular we have used phage display methods to analyse the autoantibody repertoire of thyroid disease patients.
Recombinant antibody technology is a major component of our research efforts, and we are using this approach in a number of areas, including the analysis of human autoimmune disease and the development of novel therapeutics. Aside from recombinant antibodies we have also employed phage display strategies to identify novel human autoantigens by synthesis and screening of cDNA expression libraries.
In a further development of our research effort we are now employing these techniques commercially in the rational design of novel antibody-based enzyme antagonists for use as therapeutic agents in the treatment of chronic kidney disease. This work is funded by the MRCT.

Teaching Interests

I lecture in Phase 1b (GU and Endocrine). I also teach on Module MBB311 'Molecular Immunology', and I am Module Coordinator for Module MBB334 'The Biochemical Basis of Human Disease', both in the Department of Molecular Biology and Biotechnology

Professional Activities

Member of Society for Immunology
Member of Society for Endocrinology - Regional Liaison Officer

Representative Publications

Waterman, E. A., Gawkrodger, D. J., Watson, P. F., Weetman, A. P. & Kemp, E. H. (2010) Autoantigens in vitiligo identified by the serological selection of a phage-displayed melanocyte cDNA expression. J Invest Dermatol 130, 230-240.

Kemp, E. H., Gavalas, N. G., Krohn, K. J., Brown, E. M., Watson, P. F., and Weetman, A. P. (2009) Activating autoantibodies against the calcium-sensing receptor detected in two patients with autoimmune polyendocrine syndrome type 1, J Clin Endocrinol Metab 94, 4749-4756.

Canton, I., Sarwar, U., Kemp, E.H., Watson, P.F., Ryan, A.J., MacNeil, S. and Haycock, J.W. (2007) Real time detection of stress in 3D tissue engineered constructs using NF-kB activation in transiently transfected human dermal fibroblasts. Tissue Engineering 13, 1076-3279.

Gavalas, N.G., Kemp, E.H., Krohn, K.J.E., Brown, E.M., Watson, P.F. and Weetman, A.P. (2007) The calcium-sensing receptor is a target of autoantibodies in patients with autoimmune polyendocrine syndrome type 1. Journal of Clinical Endocrinology and Metabolism 92,2107-2114.

Gavalas, N.G., Akhtar, S., Gawkrodger, D.J., Watson, P.F., Weetman, A.P. and Kemp, E.H. (2006) Analysis of allelic variants in the catalase gene in patients with the skin depigmenting disorder vitiligo. Biochemical and Biophysical Research Communications,345,1586-1591.

Mewar, D., Moore, D.J., Young-Min, S., Bertolaccini, M.L., Khamashta, M.A., Watson, P.F. and Wilson, A.G. (2005) Antiferritin antibodies discovered by phage display expression cloning are associated with radiographic damage in rheumatoid arthritis. Arthritis and Rheumatism, 52,3868-3872.

Canton, I., Akhtar, S., Gavalas, N.G., Gawkrodger, D.J., Blomhoff, A., Watson, P.F., Weetman, A.P. and Kemp, E.H. (2005) A single-nucleotide polymorphism in the gene encoding lymphoid protein tyrosine phosphatase (PTPN22) confers susceptibility to generalised vitiligo. Genes and Immunity, 6,584-587.

Gora, M., Gardas, A., Watson, P.F., Hobby, P., Weetman, A.P., Sutton, B.J. and Banga, J.P. (2004) Key residues contributing to dominant conformational autoantigenic epitopes on thyroid peroxidase identified by mutagenesis. Biochemical and Biophysical Research Communications, 320,795-801.

Barrett, K., Liakata, E., Rao, P.V., Watson, P.F., Weetman, A.P., Lymberi, P., Banga, J.P. and Carayanniotis, G. (2004) Induction of hyperthyroidism in mice by intradermal immunization with DNA encoding the thyrotropin receptor. Clinical and Experimental Immunology, 136,413-422.

Gora, M., Gardas, A., Wiktorowicz, W., Hobby, P., Watson, P.F., Weetman, A.P., Sutton, B.J. and Banga, J.P. (2004) Evaluation of conformational epitopes on thyroid peroxidase by antipeptide antibody binding and mutagenesis. Clinical and Experimental Immunology, 136,137-144.

Yang, B., Johnson, T.S., Haylor, J.L., Wagner, B., Watson, P.F., El Kossi, M.M.H., Furness, P.N. and El Nahas, A.M. (2003) Effects of caspase inhibition on the progression of experimental glomerulonephritis. Kidney International, 63,2050-2064.

Rao, P.V., Watson, P.F., Weetman, A.P., Carayanniotis, G. and Banga, J.P. (2003) Contrasting activities of thyrotropin receptor antibodies in experimental models of Graves' disease induced by injection of transfected fibroblasts or deoxyribonucleic acid vaccination. Endocrinology, 144,260-266.

Current Grants

Design and Synthesis of Transglutaminase Antagonists - MRCT