Dr Rachid Tazi-Ahnini
Department of Infection, Immunity and Cardiovascular Disease
Lecturer in Dermatology
+44 114 215 9556
Full contact details
Department of Infection, Immunity and Cardiovascular Disease
The Medical School
Beech Hill Road
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.
- Research interests
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).
- 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.
- 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). View this article in WRRO
- Investigation of four novel male androgenetic alopecia susceptibility loci: no association with female pattern hair loss. Archives of Dermatological Research, 306(4), 413-418.
- 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.
- Investigation of six novel susceptibility loci for male androgenetic alopecia in women with female pattern hair loss. Journal of Dermatological Science, 72(2), 186-188.
- 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.
- 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.
- 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.
- A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.. Nat Genet, 42(11), 985-990.
- 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.
- New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions.. J Allergy Clin Immunol, 118(1), 3-21.
- 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.
- 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.
- Corneodesmosin (MHC S) gene in guttate psoriasis.. Lancet, 354(9178), 597.
- Research group
- 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
- Teaching interests
- Professional activities
- 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