Dr Philip F Watson
Department of Oncology and Metabolism
+44 114 215 9228
Full contact details
Department of Oncology and Metabolism
EU05, E Floor
The Medical School
Beech Hill Road
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 centre 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.
- Interplay between transglutaminases and heparan sulphate in progressive renal scarring. Scientific Reports, 6(1). View this article in WRRO
- IL‐14 and IL‐16 are expressed in the thyroid of patients with either Graves’ disease or Hashimoto's thyroiditis. Clinical Endocrinology, 83, 726-732. View this article in WRRO
- Low frequency of pendrin autoantibodies detected using a radioligand binding assay in patients with autoimmune thyroid disease.. J Clin Endocrinol Metab, 98(2), E309-E313.
- A crucial sequence for transglutaminase type 2 extracellular trafficking in renal tubular epithelial cells lies in its N-terminal beta-sandwich domain.. J Biol Chem, 286(31), 27825-27835.
- Autoantibodies against tyrosine hydroxylase in patients with non-segmental (generalised) vitiligo.. Exp Dermatol, 20(1), 35-40.
- Development of a 3D human in vitro skin co-culture model for detecting irritants in real-time.. Biotechnol Bioeng, 106(5), 794-803.
- Autoantigens in vitiligo identified by the serological selection of a phage-displayed melanocyte cDNA expression library.. J Invest Dermatol, 130(1), 230-240.
- Mapping of human autoantibody binding sites on the calcium-sensing receptor.. J Bone Miner Res, 25(1), 132-140. View this article in WRRO
- Activating autoantibodies against the calcium-sensing receptor detected in two patients with autoimmune polyendocrine syndrome type 1.. J Clin Endocrinol Metab, 94(12), 4749-4756.
- Mapping of melanin-concentrating hormone receptor 1 B cell epitopes predicts two major binding sites for vitiligo patient autoantibodies.. Exp Dermatol, 18(5), 454-463.
- The calcium-sensing receptor is a target of autoantibodies in patients with autoimmune polyendocrine syndrome type 1.. J Clin Endocrinol Metab, 92(6), 2107-2114.
- Function-blocking autoantibodies to the melanin-concentrating hormone receptor in vitiligo patients.. Lab Invest, 86(8), 781-789.
- Analysis of allelic variants in the catalase gene in patients with the skin depigmenting disorder vitiligo.. Biochem Biophys Res Commun, 345(4), 1586-1591.
- Identification of a monoclonal antibody against the leptin receptor that acts as an antagonist and blocks human monocyte and T cell activation. Journal of Immunological Methods, 312(1-2), 190-200.
- Antiferritin antibodies discovered by phage display expression cloning are associated with radiographic damage in rheumatoid arthritis.. Arthritis Rheum, 52(12), 3868-3872.
- A single-nucleotide polymorphism in the gene encoding lymphoid protein tyrosine phosphatase (PTPN22) confers susceptibility to generalised vitiligo.. Genes Immun, 6(7), 584-587.
- An insertion/deletion polymorphism in the gene encoding angiotensin converting enzyme is not associated with generalised vitiligo in an English population.. Arch Dermatol Res, 297(2), 94-98.
- Key residues contributing to dominant conformational autoantigenic epitopes on thyroid peroxidase identified by mutagenesis.. Biochem Biophys Res Commun, 320(3), 795-801.
- Induction of hyperthyroidism in mice by intradermal immunization with DNA encoding the thyrotropin receptor.. Clin Exp Immunol, 136(3), 413-422.
- Evaluation of conformational epitopes on thyroid peroxidase by antipeptide antibody binding and mutagenesis.. Clin Exp Immunol, 136(1), 137-144.
- Autoantibodies in vitiligo patients recognize multiple domains of the melanin-concentrating hormone receptor.. J Invest Dermatol, 121(4), 765-770.
- Detection and localization of chemokine gene expression in autoimmune thyroid disease.. Clin Endocrinol (Oxf), 59(2), 207-213.
- HLA-G does not have a pathophysiological role in Graves' disease.. J Clin Pathol, 56(6), 475-477.
- Effects of caspase inhibition on the progression of experimental glomerulonephritis.. Kidney Int, 63(6), 2050-2064.
- AUTOANTIBODIES TO EUKARYOTIC TRANSCRIPTON ELONGATION FACTOR 1 ALPHA 1 IN SYSTEMIC AUTOIMMUNE DISEASES. RHEUMATOLOGY, 42, 72-72.
- Contrasting activities of thyrotropin receptor antibodies in experimental models of Graves' disease induced by injection of transfected fibroblasts or deoxyribonucleic acid vaccination.. Endocrinology, 144(1), 260-266.
- Immunoscreening of phage-displayed cDNA-encoded polypeptides identifies B cell targets in autoimmune disease.. Biochem Biophys Res Commun, 298(1), 169-177.
- A shift in the Bax/Bcl-2 balance may activate caspase-3 and modulate apoptosis in experimental glomerulonephritis.. Kidney Int, 62(4), 1301-1313.
- Autoantibodies in vitiligo patients are not directed to the melanocyte differentiation antigen MelanA/MART1.. Clin Exp Immunol, 129(3), 527-532.
- Demonstration of immunoglobulin G, A, and E autoantibodies to the human thyrotropin receptor using flow cytometry.. J Clin Endocrinol Metab, 87(4), 1754-1761.
- Mutations of the PDS gene, encoding pendrin, are associated with protein mislocalization and loss of iodide efflux: implications for thyroid dysfunction in Pendred syndrome.. J Clin Endocrinol Metab, 87(4), 1778-1784.
- The melanin-concentrating hormone receptor 1, a novel target of autoantibody responses in vitiligo.. J Clin Invest, 109(7), 923-930.
- Caspase-3 and apoptosis in experimental chronic renal scarring.. Kidney Int, 60(5), 1765-1776.
- Pendred syndrome mutations in the PDS gene cause a loss of iodide transport function and protein mislocalisation.. AM J HUM GENET, 69(4), 590-590.
- Is there loss or qualitative changes in the expression of thyroid peroxidase protein in thyroid epithelial cancer?. Br J Cancer, 85(6), 875-880. View this article in WRRO
- Molecular mapping of epitopes on melanocyte-specific protein Pmel17 which are recognized by autoantibodies in patients with vitiligo.. Clin Exp Immunol, 124(3), 509-515.
- Identification of antigenic domains on the human sodium-iodide symporter which are recognized by autoantibodies from patients with autoimmune thyroid disease.. Clin Exp Immunol, 124(3), 377-385.
- Apoptosis and caspase-3 in experimental anti-glomerular basement membrane nephritis.. J Am Soc Nephrol, 12(3), 485-495.
- Expression of apoptosis-related genes and proteins in experimental chronic renal scarring.. J Am Soc Nephrol, 12(2), 275-288.
- Autoantibodies to the flavoprotein subunit of succinate dehydrogenase: analysis of specificity in autoimmune thyroid disease.. Clin Endocrinol (Oxf), 53(3), 291-299.
- High-dose growth hormone does not affect proinflammatory cytokine (tumor necrosis factor-alpha, interleukin-6, and interferon-gamma) release from activated peripheral blood mononuclear cells or after minimal to moderate surgical stress.. J Clin Endocrinol Metab, 85(9), 3383-3390.
- Detection of binding and blocking autoantibodies to the human sodium-iodide symporter in patients with autoimmune thyroid disease.. J Clin Endocrinol Metab, 85(5), 2020-2027.
- Human thyroid peroxidase: mapping of autoantibodies, conformational epitopes to the enzyme surface.. Redox Rep, 5(4), 237-241.
- Effects of transforming growth factor-β1 on renal extracellular matrix components and their regulating proteins. Journal of the American Society of Nephrology, 10(10), 2109-2119.
- Identification of epitopes on tyrosinase which are recognized by autoantibodies from patients with vitiligo.. J Invest Dermatol, 113(2), 267-271.
- Analysis of a microsatellite polymorphism of the cytotoxic T-lymphocyte antigen-4 gene in patients with vitiligo.. Br J Dermatol, 140(1), 73-78.
- Autoantibodies to human melanocyte-specific protein pmel17 in the sera of vitiligo patients: a sensitive and quantitative radioimmunoassay (RIA).. Clin Exp Immunol, 114(3), 333-338.
- Autoantibodies to tyrosinase-related protein-1 detected in the sera of vitiligo patients using a quantitative radiobinding assay.. Br J Dermatol, 139(5), 798-805.
- A new chemiluminescent assay for the rapid detection of thyroid stimulating antibodies in Graves' disease.. Clin Endocrinol (Oxf), 49(5), 577-581.
- A cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism is associated with autoimmune Addison's disease in English patients.. Clin Endocrinol (Oxf), 49(5), 609-613.
- Regulation and tissue distribution of the human sodium iodide symporter gene.. Clin Endocrinol (Oxf), 49(4), 517-523.
- The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity.. J Endocrinol, 158(3), 351-358.
- Comparative mapping of cloned human and murine antithyroglobulin antibodies: recognition by human antibodies of an immunodominant region.. Thyroid, 8(8), 643-646.
- A study of the association between a polymorphism in the CTLA-4 gene and postpartum thyroiditis.. Clin Endocrinol (Oxf), 49(2), 251-255.
- Somatic hypermutation in antoimmune thyroid disease. Immunological Reviews, 162(1), 219-231.
- The modulation of the human sodium iodide symporter activity by Graves' disease sera.. J Clin Endocrinol Metab, 83(4), 1217-1221.
- Analysis of the T-cell receptor Valpha repertoire and cytokine gene expression in Sjögren's syndrome.. Br J Rheumatol, 37(2), 179-185.
- Analysis of immunoglobulin G kappa antithyroid peroxidase antibodies from different tissues in Hashimoto's thyroiditis.. J Clin Endocrinol Metab, 82(11), 3818-3825.
- Cytokines and Graves' disease.. Baillieres Clin Endocrinol Metab, 11(3), 481-497.
- Immunoprecipitation of melanogenic enzyme autoantigens with vitiligo sera: evidence for cross-reactive autoantibodies to tyrosinase and tyrosinase-related protein-2 (TRP-2).. Clin Exp Immunol, 109(3), 495-500.
- Immunoglobulin G kappa antithyroid peroxidase antibodies in Hashimoto's thyroiditis: epitope-mapping analysis.. J Clin Endocrinol Metab, 82(8), 2639-2644.
- Detection of tyrosinase autoantibodies in patients with vitiligo using 35S-labeled recombinant human tyrosinase in a radioimmunoassay.. J Invest Dermatol, 109(1), 69-73.
- A CTLA-4 gene polymorphism is associated with both Graves disease and autoimmune hypothyroidism.. Clin Endocrinol (Oxf), 46(5), 551-554.
- The pattern of cytokine mRNA expression in ovarian endometriomata.. Mol Hum Reprod, 3(5), 393-397.
- Analysis of the T Cell Receptor Vα Repertoire in Hashimoto’s Thyroiditis: Evidence for the Restricted Accumulation of CD8+T Cells in the Absence of CD4+T Cell Restriction1. The Journal of Clinical Endocrinology & Metabolism, 82(4), 1140-1146.
- Analysis of the T cell receptor V alpha repertoire in Hashimoto's thyroiditis: evidence for the restricted accumulation of CD8+ T cells in the absence of CD4+ T cell restriction.. J Clin Endocrinol Metab, 82(4), 1140-1146.
- No association between a thyrotropin receptor gene polymorphism and Graves' disease in the female population.. Thyroid, 7(1), 31-33.
- Detection of IL-12, IL-13, and IL-15 messenger ribonucleic acid in the thyroid of patients with autoimmune thyroid disease.. J Clin Endocrinol Metab, 82(2), 666-669.
- Intrathyroidal cytokine gene expression in Hashimoto's thyroiditis.. Clin Exp Immunol, 105(3), 523-528.
- Cloning and analysis of IgG kappa and IgG lambda anti-thyroglobulin autoantibodies from a patient with Hashimoto's thyroiditis: evidence for in vivo antigen-driven repertoire selection.. J Immunol, 157(2), 927-935.
- Association of HLA-DQA1*0501 with Graves’ disease in English Caucasian men and women. Clinical Endocrinology, 44(1), 73-77.
- Cytokines and thyroid function.. Adv Neuroimmunol, 6(4), 359-386.
- Semi-quantitative analysis of interleukin-1 alpha, interleukin-6 and interleukin-8 mRNA expression by human thyrocytes.. J Mol Endocrinol, 15(1), 11-21.
- Lack of association between a polymorphism in the coding region of the thyrotropin receptor gene and Graves' disease.. J Clin Endocrinol Metab, 80(3), 1032-1035.
- Association of Graves' disease with an allele of the interleukin-1 receptor antagonist gene.. J Clin Endocrinol Metab, 80(1), 111-115.
- Analysis of cytokine gene expression in Graves' disease and multinodular goiter.. J Clin Endocrinol Metab, 79(2), 355-360.
- Treatment of Graves' disease with the block-replace regimen of antithyroid drugs: the effect of treatment duration and immunogenetic susceptibility on relapse.. QJM, 87(6), 337-341.
- T cell receptor beta chain gene polymorphisms in Graves' disease.. Acta Endocrinol (Copenh), 128(6), 499-502.
- No restriction of intrathyroidal T cell receptor V alpha families in the thyroid of Graves' disease.. Clin Exp Immunol, 91(1), 147-152.
- Catalytic activities of human debrisoquine 4-hydroxylase cytochrome P450 (CYP2D6) expressed in yeast.. Biochem Pharmacol, 44(4), 617-620.
- Molecular genetic studies on the mode of action of azole antifungal agents.. Biochem Soc Trans, 19(3), 796-798.
- Defective sterol C5-6 desaturation and azole resistance: a new hypothesis for the mode of action of azole antifungals.. Biochem Biophys Res Commun, 164(3), 1170-1175.
- Genetic and physiological analysis of azole sensitivity in Saccharomyces cerevisiae.. J Med Vet Mycol, 27(6), 397-406.
- Isolation and analysis of ketoconazole resistant mutants of Saccharomyces cerevisiae.. J Med Vet Mycol, 26(3), 153-162.
- Isolation and analysis of ketoconazole resistant mutants ofSaccharomyces cerevisiae. Medical Mycology, 26(3), 153-162.
- Treatment of Graves' disease with the block-replace regimen of antithyroid drugs: the effect of treatment duration and immunogenetic susceptibility on relapse. QJM: An International Journal of Medicine.
- Orbital Autoantigens In Bahn RS (Ed.), Thyroid Eye Disease (pp. 1-20). Dordrecht, The Netherlands: Springer.
- Cytokines in Graves’ Disease, Endocrine Updates (pp. 79-93). Springer US
- Autoimmune hypothyroidism, Endocrine Autoimmunity and Associated Conditions (pp. 39-61). Springer Netherlands
- Lanosterol to Ergosterol — Enzymology, Inhibition and Genetics, Biochemistry of Cell Walls and Membranes in Fungi (pp. 223-243). Springer Berlin Heidelberg
Conference proceedings papers
- The potential role of a selective carboxypeptidase B2 inhibitor UK-396082 in diabetic nephropathy. International Journal of Experimental Pathology, Vol. 98(3) (pp A7-A7), 3 April 2017 - 4 April 2017.
- Layering Interventions for Type-2 Diabetes Prevention Using The Sphr Diabetes Model. Value in Health, Vol. 17(7) (pp A347-A347)
- Validation of the SPHR Diabetes Prevention Model. Value in Health, Vol. 17(7) (pp A556-A556)
- The expected value of sample information from the pharmaceutical perspective under conditions of value based pricing. Value in Health, Vol. 16(3) (pp A29-A29)
- Autoantibodies to ferritin in rheumatoid arthritisRheumatoid arthritis. RHEUMATOLOGY, Vol. 44 (pp I61-I61)
- Antibodies to ferritin in rheumatoid arthritis are associated with disease severity. ARTHRITIS RESEARCH & THERAPY, Vol. 7 (pp S47-S47) View this article in WRRO
- Generation and screening of a phage-displayed cDNA library from the rheumatoid synovium.. ARTHRITIS AND RHEUMATISM, Vol. 48(9) (pp S342-S342)
- 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