Dr Rachid Tazi-Ahnini
Lecturer in Dermatology
Department of Infection, Immunity & Cardiovascular Disease
University of Sheffield
Beech Hill Road
Tel: +44(0) 114 215 9556
Fax: +44(0) 114 271 1863
I studied for my Bachelor´s and Master´s degrees in molecular and cellular biology at the University Paul Sabatier, Toulouse III-France. In 1994 I began PhD studies in human genetics at the laboratories of "Centre National de Recherche Scientifique", Toulouse. As part of my PhD, I worked on positional cloning of multigenic family butyrophilin, located in the distal part of the major histocompatibility complex (MHC). I moved to Britain for a postdoctoral appointment in 1997at the University of Sheffield. Because of my background in MHC structure, evolution and genetics, I subsequently focussed most of my work on the genetics of the MHC in psoriasis and alopecia areata. In January 2000, I was appointed by the University of Sheffield to the post of Lecturer in Molecular Dermatology to develop genetic studies of inflammatory skin diseases including alopecia areata, psoriasis, atopic dermatitis and vitiligo. Recently, I become very interested in understanding the mechanism underlining the pathogenesis of some autoimmune diseases such as alopecia areata, vitiligo and thyroid diseases. I am particularly interested in identifying auto-antigens involved in the pathogenesis of these diseases.
My research interests are determination of the function of the autoimmune regulator (AIRE) gene and its role in the pathogenesis of some autoimmune diseases such as alopecia areata, vitiligo and thyroid diseases. In our department, we are using Autoimmune Polyglandular Syndrome type I (APS-1) as a model to study the pathogenesis of these disorders. APS-1 is a rare disorder characterised by an unusual pathogenesis within the range of autoimmune disorders, most of which are more typically polygenic traits such as hypoparathyroidism and Addison´s disease, diabetes, alopecia areata and vitiligo. APS-1 is an autosomal recessive disorder caused by loss-of-function mutations of the Autoimmune Regulator (AIRE) gene located at chromosome 21q22.3.
I am also interested in the genetics of some skin diseases such as psoriasis, atopic dermatitis, alopecia areata and vitiligo. We use a genome-wide association study to identify genetic loci of these diseases. Candidate genes within susceptibility loci are screened for single nucleotide polymorphisms (SNPs) and the distribution of each SNP is then compared between cases and controls. We also used transmissions disequilibrium tests (TDT) to test for transmission distortion of SNPs or haplotypes using trios (patient and parents).
- Founder and Director of The Medical Research Summer Programme, a new teaching scheme at the University of Sheffield.
- I am a research project module leader for the MSc in Molecular Medicine.
- Other teaching activities include supervising and monitoring MB ChB, MSc and PhD students.
- Regular reviewer for several Molecular Dermatology and Human Molecular Genetics journals.
- Reviewer for national and international grants.
- Member of Organising Committee of the 7th World Congress for Hair Research I Edinburgh, 4-6th May, 2013; www.hair2013.org/committee.asp
- AIRE encodes for a transcription factor that has been found to regulate the promiscuous expression of tissue restricted antigens in the thymus. This function increases the repertoire of antigens presented in the thymus for negative selection of immature thymocytes in the central tolerance process. We are investigating the effects of polymorphisms in the AIRE promoter on AIRE expression as well as the mechanism of AIRE regulated gene expression. We are using site-specific recombination techniques to generate a variety of different human cell line models with which to investigate the function and regulation of AIRE.
- The role of the autoimmune regulator (AIRE) gene is fundamental to alopecia areata (AA) arising in the autoimmune polyendocrine syndrome type 1 (APS-1) and we are currently analysing the role of AIRE in sporadic AA cases using a cellular model of thymic cell gene expression. Demonstration that autoantigens identified in AA cases non-associated with APS-1 are also regulated by the AIRE gene would strongly support the role of AIRE in the pathogenesis of AA.
Refinement of the identity and role of autoantigens in this complex polygenic disorder also has the potential to provide new insights into the pathogenesis of a spectrum of organ-specific autoimmune diseases which occur more commonly in patients and families with AA such as vitiligo and autoimmune thyroid disease.
- Dr Thomas Lovewell, post-doctoral Research Assistant, 2008-present, funded by The Ministry of High Education, Saudi Arabia
- Dr Osama Al-Amer, post-doctoral Research Assistant, funded by The Ministry of High Education, Saudi Arabia, 2014-16,
- Dr Fatma Hamed, PhD student, 2014-16, funded by the Libyan Government he Ministry of High Education
- Mrs Sarah Al-Maghribi. PhD student, 2014-16, funded by The Ministry of High Education, Saudi Arabia
- Dr Wael Al-Daraji, PhD student, 2014-16, self-funded
For key publications see below. For a full list of publications click here.
- Lovewell TRJ, McDonagh AJG, Messenger AG, Azzouz M & Tazi-Ahnini R (2018) Meta-analysis of autoimmune regulator-regulated genes in human and murine models: A novel human model provides insights on the role of autoimmune regulator in regulating STAT1 and STAT1-regulated genes. Frontiers in Immunology, 9(JUN).
- Nuwaihyd R, Redler S, Heilmann S, Drichel D, Wolf S, Birch P, Dobson K, Lutz G, Giehl KA, Kruse R, Tazi-Ahnini R, Hanneken S, Böhm M, Miesel A, Fischer T, Wolff H, Becker T, Garcia-Bartels N, Blume-Peytavi U, Nöthen MM, Messenger AG & Betz RC (2014) Investigation of four novel male androgenetic alopecia susceptibility loci: no association with female pattern hair loss. Archives of Dermatological Research, 306(4), 413-418.
- Redler S, Birch P, Drichel D, Hofmann P, Dobson K, Böhmer AC, Becker J, Giehl KA, Tazi-Ahnini R, Kruse R, Wolff H, Miesel A, Fischer T, Böhm M, Nuwayhid R, Garcia Bartels N, Lutz G, Becker T, Blume-Peytavi U, Nöthen MM, Messenger AG & Betz RC (2014) The oestrogen receptor 2 (ESR2) gene in female-pattern hair loss: replication of association with rs10137185 in German patients. British Journal of Dermatology, 170(4), 982-985.
- • Redler S, Dobson K, Drichel D, Heilmann S, Wolf S, Brockschmidt FF, Tazi-Ahnini R, Birch P, Teßmann P, Giehl KA, Kruse R, Lutz G, Garcia Bartels N, Hanneken S, Wolff H, Böhm M, Becker T, Blume-Peytavi U, Nöthen MM, Messenger AG, Betz RC (2013) Investigation of six novel susceptibility loci for male androgenetic alopecia in women with female pattern hair loss.
- Redler S, Brockschmidt FF, Tazi-Ahnini R, Drichel D, Birch MP, Dobson K, Giehl KA, Herms S, Refke M, Kluck N, Kruse R, Lutz G, Wolff H, Böhm M, Becker T, Nöthen MM, Messenger AG & Betz RC (2012) Investigation of the male pattern baldness major genetic susceptibility loci AR/EDA2R and 20p11 in female pattern hair loss. British Journal of Dermatology, 166(6), 1314-1318.
- Vasilopoulos Y, Sagoo GS, Cork MJ, Walters K & Tazi-Ahnini R (2011) HLA-C, CSTA and DS12346 susceptibility alleles confer over 100-fold increased risk of developing psoriasis: evidence of gene interaction.. J Hum Genet, 56(6), 423-427.
- Vasilopoulos Y, Sharaf N, di Giovine F, Simon M, Cork MJ, Duff GW & Tazi-Ahnini R (2011) The 3'-UTR AACCins5874 in the stratum corneum chymotryptic enzyme gene (SCCE/KLK7), associated with atopic dermatitis; causes an increased mRNA expression without altering its stability.. J Dermatol Sci, 61(2), 131-133.
- Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2 , Strange A, Capon F, Spencer CCA, Knight J, Weale ME, Allen MH, Barton A, Band G, Bellenguez C, Bergboer JGM, Blackwell JM, Bramon E, Bumpstead SJ, Casas JP, Cork MJ, Corvin A, Deloukas P, Dilthey A, Duncanson A, Edkins S, Estivill X, Fitzgerald O, Freeman C, Giardina E, Gray E, Hofer A, Hüffmeier U, Hunt SE, Irvine AD, Jankowski J, Kirby B, Langford C, Lascorz J, Leman J, Leslie S, Mallbris L, Markus HS, Mathew CG, McLean WHI, McManus R, Mössner R, Moutsianas L, Naluai AT, Nestle FO, Novelli G, Onoufriadis A, Palmer CNA, Perricone C, Pirinen M, Plomin R, Potter SC, Pujol RM, Rautanen A, Riveira-Munoz E, Ryan AW, Salmhofer W, Samuelsson L, Sawcer SJ, Schalkwijk J, Smith CH, Ståhle M, Su Z, Tazi-Ahnini R, Traupe H, Viswanathan AC, Warren RB, Weger W, Wolk K, Wood N, Worthington J, Young HS, Zeeuwen PLJM, Hayday A, Burden AD, Griffiths CEM, Kere J, Reis A, McVean G, Evans DM, Brown MA, Barker JN, Peltonen L, Donnelly P & Trembath RC (2010) A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.. Nat Genet, 42(11), 985-990.
- Vasilopoulos Y, Cork MJ, Teare D, Marinou I, Ward SJ, Duff GW & Tazi-Ahnini R (2007) A nonsynonymous substitution of cystatin A, a cysteine protease inhibitor of house dust mite protease, leads to decreased mRNA stability and shows a significant association with atopic dermatitis.. Allergy, 62(5), 514-519.
- Cork MJ, Robinson DA, Vasilopoulos Y, Ferguson A, Moustafa M, MacGowan A, Duff GW, Ward SJ & Tazi-Ahnini R (2006) New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions.. J Allergy Clin Immunol, 118(1), 3-21.
- Lench N, Iles MM, Mackay I, Patel R, Sagoo GS, Ward SJ, Dechairo B, Olavesen M, Carey A, Duff GW, Cork MJ & Tazi-Ahnini R (2005) Single-point haplotype scores telomeric to human leukocyte antigen-C give a high susceptibility major histocompatibility complex haplotype for psoriasis in a Caucasian population.. J Invest Dermatol, 124(3), 545-552.
- Vasilopoulos Y, Cork MJ, Murphy R, Williams HC, Robinson DA, Duff GW, Ward SJ & Tazi-Ahnini R (2004) Genetic association between an AACC insertion in the 3'UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis.. J Invest Dermatol, 123(1), 62-66.
- Tazi-Ahnini R, di Giovine FS, Cox A, Keohane SG & Cork MJ (1999) Corneodesmosin (MHC S) gene in guttate psoriasis.. Lancet, 354(9178), 597.