Wellcome Trust Senior Research Fellow in Clinical Science, Professor of Molecular & Genetic Dermatology
Understanding molecular & genetic mechanisms in atopic skin
Clinical Research Centre Level 7
Ninewells Hospital and Medical School
University of Dundee
James Arrott Drive
+(44) 01382 383210
Professor Sara Brown graduated with Honours in Medicine & Surgery from the University of Edinburgh and gained her specialist training in Dermatology in Newcastle-upon-Tyne. Sara obtained an MD in Human Genetics with commendation in 2008 for her research looking at the role of filaggrin null mutations in a population-based cohort study, working with Nick Reynolds, John Burn and Heather Cordell.
Sara was awarded a Wellcome Trust Intermediate Clinical Fellowship in 2009 and spent 10 months as a Post-CCT Fellow in Paediatric Dermatology in Dublin, Ireland, with Alan Irvine & Rosemarie Watson.
Sara moved to Dundee in October 2009, working within Irwin McLean’s laboratory and as a clinical collaborator in ‘DGEM’, the Wellcome Trust-funded Centre for Dermatology & Genetic Medicine.
Sara has now established her own laboratory, based in the Medical Research Institute within Ninewells Hospital and Medical School, Dundee. In May 2015 Sara became the first UK dermatologist to be awarded a prestigious Wellcome Trust Senior Research Fellowship in Clinical Science and in October 2015 she was given a personal chair of Molecular and Genetic Dermatology.
Sara is a member of the following national committees:
- UK Translational Research Network in Dermatology (UK-TREND)
- British Society for Investigative Dermatology
- British Association of Dermatologists’ Dermatology & Genetic Medicine (BADGEM)
- Dermatogenetics – a subgroup of the British Society for Genetic Medicine
- Dermatology Council for Scotland, Clinical Academic Representative
Other roles & responsibilities:
- Grant reviewer for the Wellcome Trust, Medical Research Council, British Skin Foundation, Action Medical Research and the Medical Research Council Scotland.
- Member of European Epidermal Barrier Research Network (E2BRN) (2014-)
- Associate Editor (Translational Medicine) British Journal of Dermatology (2015-)
Genetic mechanisms in atopic eczema
Atopic eczema is an itchy inflammatory skin disease, which has increased in prevalence over recent decades. It is a complex trait, arising from the interaction of multiple genetic and environmental factors, but eczema is highly heritable, demonstrating the importance of genetic predisposition.
Multiple risk loci have been identified by genomewide association studies, but a locus on chromosome 1q21 shows the strongest association. Within this locus, loss-of-function mutations in the gene encoding the skin barrier protein filaggrin (FLG) are well known to increase risk of atopic eczema. Sara’s work, in collaboration with Irwin McLean and Alan Irvine, has contributed to defining the role of FLG in every step of the ‘atopic march’, including mild, moderate and severe eczema, atopic asthma, allergic rhinitis and peanut allergy. Her work has shown that copy number variation within FLG has a dose-dependent effect on eczema risk, indicating that treatments aimed at increasing filaggrin expression may be of therapeutic benefit.
Sara was the first to apply single molecule RNA sequencing for detailed analysis of atopic skin. Detailed analysis, performed in collaboration with the Data Analysis Group, University of Dundee, has highlighted an increased stress response in filaggrin-deficient skin and dysregulation of lipid networks in FLG wild type skin. Sara has also contributed to major international collaborative work on genome-wide analysis in eczema, within the EAGLE consortium, and in collaboration with Heather Cordell (Newcastle University).
In her current work, Sara will use next generation sequencing to investigate copy number variation in genes related to FLG. She is also developing organotypic skin culture to test the role of candidate genes/transcripts for which functional mechanisms are currently unknown. This will move towards identifying targets for much-needed therapy development.
Sara’s personal grant income has totalled over £2.4 million in the last 6 years and she is grateful to acknowledge the support of the Wellcome Trust, the Manknell Charitable Trust and the Tayside Dermatological Research Charity.
Watch a 3-minute video of Sara describing her work, motivation and long-term aims https://youtu.be/fWuNpI1wTUs
Selected peer-reviewed publications within the past 5 years:
1. Thomas KS, Bradshaw LE, Sach TH, Batchelor JM, Lawton S, Harrison EF, Haines RH, Ahmed A, Williams HC, Dean T, Burrows NP, Pollock I, Llewellyn J, Crang C, Grundy JD, Guiness J, Gribbin A, Mitchell EJ, Cowdell F, Brown SJ and Montgomery AA (UK Dermatology Clinical Trials Network’s CLOTHES Trial Team). Silk garments plus standard care compared with standard care for treating eczema in children: A randomised, controlled, observer-blind, pragmatic trial (CLOTHES Trial) PLoS Medicine 2017; 14 (4), e1002280
2. Naeem AS, Tommasi C, Cole C, Brown SJ, Zhu Y, Way B, Willis Owen SA, Moffatt M, Cookson WO, Harper JI, Wl D, Brown SJ, Reinheckel T, O'Shaughnessy RF. An mTORC1/AKT1/Cathepsin H axis controls filaggrin expression and processing in skin, a novel mechanism for skin barrier disruption in Atopic Dermatitis. J Allergy Clin Immunol. 2017 Apr;139(4):1228-1241.
3. Forbes D, Johnston L, Gardner J, MacCallum SF, Campbell LE, Dinkova-Kostova A, McLean WHI, Ibbotson SH, Dawe RS and Brown SJ. Filaggrin genotype does not determine the skin's threshold to UV-induced erythema J Allergy Clin Immunol 2016 Apr;137(4):1280-2.
4. Paternoster L, Standl M, Waage J, Baurecht H, Hotze M et al. Glass D, Brown SJ, Heinrich J, Evans DM* and Weidinger S.* (joint senior authors*). Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet. 2015;47(12):1449-56.
5. Healy E, Brown SJ, Langan S, Nicholls SG, Shams K and Reynolds NJ, on behalf of UK TREND. Identification of Translational Dermatology Research Priorities in the UK; Results of an e-Delphi Exercise. Br J Dermatol 2015 Nov;173(5):1191-8.
6. Harkins CP, Waters A, Kerr A, Campbell L, McLean WH, Brown SJ* and Ibbotson SH* (*joint senior authors). Loss-of-function mutations in the gene encoding filaggrin are not strongly associated with chronic actinic dermatitis. J Invest Dermatol. 2015; 135(7):1919-21.
7. Baurecht H,* Hotze M,* Brand S, Büning C, Cormican P, Corvin A, Ellinghaus D, Ellinghaus E, Esparza-Gordillo J, Fölster-Holst R, Franke A, Gieger C, Hubner N, Illig T, Irvine AD, Kabesch M, Lee Y AE, Lieb W, Marenholz I, McLean WHI, Morris DW, Mrowietz U, Nair R, Nöthen MM, Novak N, O’Regan GM, PAGE consortium, Schreiber S, Smith C, Strauch K, Stuart PE, Trembath R, Tsoi LC, Weichenthal M, Barker J, Elder JT, Weidinger S,* Cordell HJ,* and Brown SJ.* [* contributed equally]. Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms. Am J Hum Genet. 2015 Jan 8;96(1):104-20.
8. Brough HA, Simpson A, Makinson K, Hankinson J, Brown S, Douiri A, Belgrave DC, Penagos M, Stephens AC, McLean WH, Turcanu V, Nicolaou N, Custovic A, Lack G. Peanut allergy: effect of environmental peanut exposure in children with filaggrin loss-of-function mutations. J Allergy Clin Immunol. 2014 Oct;134(4):867-875.
9. Brough HA, Liu AH, Sicherer S, Makinson K, Douiri A, Brown SJ, Stephens AC, Irwin McLean WH, Turcanu V, Wood RA, Jones SM, Burks W, Dawson P, Stablein D, Sampson H, Lack G. Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy. J Allergy Clin Immunol. 2015 Jan;135(1):164-70.
10. Simpson EL, Chalmers JR, Hanifin JM, Thomas KS, Cork MJ, McLean WH, Brown SJ, Chen Z, Chen Y, Williams HC. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol. 2014 Oct;134(4):818-23.
11. Cole C, Kroboth K, Schurch NJ, Sandilands A, Sherstnev A, et al., Watson RM, McLean WHI, Barton GJ, Irvine AD, Brown SJ. Filaggrin-stratified transcriptome analysis of paediatric skin identifies mechanistic pathways in atopic dermatitis. J Allergy Clin Immunol. 2014 Jul;134(1):82-91.
12. Schurch NJ, Cole C, Sherstnev A, Song J, Duc C, Storey KG, McLean WH, Brown SJ, Simpson GG, Barton GJ. Improved Annotation of 3’ Untranslated Regions and Complex Loci by Combination of Strand-Specific Direct RNA Sequencing, RNA-Seq and ESTs. PLoS One. 2014 Apr 10;9(4):e94270.
13. Saunders SP, Goh CSM (joint 1st authors), Brown SJ, Palmer CNA, Porter RM, Cole C, Campbell LE, Gierlinski M, Barton, GJ, Schneider G et al. Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic dermatitis in humans. J Allergy Clin Immunol 2013 Nov; 132(5):1121-9.
14. Weidinger S et al., Lieden A, Nordenskjold M, Harper JI, McLean WHI, Brown SJ, Cookson WOC, Lathrop GM, Irvine AD and Moffatt MF. A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. Human Molecular Genetics 2013 Dec 1; 22(23):4841-56.
15. Ellinghaus D et al., Fahy CM, Kabesch M, Brown S, McLean WH, Irvine AD, Schreiber S, Lee YA, Franke A, Weidinger S. High-density genotyping study identifies four new susceptibility loci for atopic dermatitis. Nat Genet. 2013 Jul;45(7):808-12.
16. Pöhler E, Zamiri M, Harkins C, Salas-Alanis JC, Perkins W, Smith FJ, McLean WHI, Brown SJ. Heterozygous mutations in AAGAB cause type 1 punctate palmoplantar keratoderma with evidence for increased growth factor signalling. J Invest Dermatol. 2013 Dec;133(12):2805-8.
17. Pohler E et al., Saad A, Gribaa M, Dopping-Hepenstal PJ, McGrath JA, Brown SJ, Goudie DR, Reversade B, Munro CS, McLean WH. Haploinsufficiency for AAGAB causes clinically heterogeneous forms of punctate palmoplantar keratoderma. Nat Genet. 2012 Nov;44(11):1272-6.
18. Sandilands A, Brown SJ, Goh CS, Pohler E, Wilson NJ, Campbell LE, Miyamoto K, Kubo A, Irvine AD, Thawer-Esmail F, et al. Mutations in the SASPase gene (ASPRV1) are not associated with atopic eczema or clinically dry skin. J Invest Dermatol. 2012;132 (5):1507-10.
19. Brown SJ, Kroboth K, Sandilands A, Campbell L, Pohler E, Kezic S, Cordell HJ, McLean WHI and Irvine AD. Intragenic copy number variation within filaggrin contributes to risk of atopic dermatitis with a dose-dependent effect. J Invest Dermatol 2012;132(1):98-104.
20. Brown SJ, Asai Y (joint 1st authors), Cordell HJ, Campbell LE, Zhao Y, Liao H, Northstone K, Henderson J, Alizadehfar R, Ben-Shoshan M, et al. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol 2011; 127(3): 661-667.
Undergraduates in Dundee:
- Medical students, in clinics
- Phase 1 dermatology-genetics teaching
- BMSc in Human Genetics & Experimental Medicine, lecturer
- SSC project supervisor
- DRAMS journal club facilitator
Postgraduate, local & national:
- Co-organiser of ‘Advanced Paediatric Dermatology Course’ held annually, in Dundee
- Lecturer and mentor on TheSIS/BAD/BSID Dermatology research course, annually since 2010
- Dundee StR Research Course, lecturer (2012 -)
- Examiner for Royal College of Physicians Diploma in Dermatology (2015 -)
- Lecturer in ‘DermSchool’, organised by the British Association of Dermatologists (2014)
- Invited speaker at British Association of Dermatologists’ CPD session (2015)
Invited talks within the last 5 years:
2016 American Academy of Allergy Asthma and Immunology annual meeting , Los Angeles, California, USA
2015 World Congress of Dermatology Special Interest Lecture, Vancouver, Canada
2015 European Academy of Dermatology and Venereology Plenary Lecture, Valencia, Spain
2014 British Society of Genetic Medicine annual meeting Dermatogenetics section, Liverpool, UK
2014 European Society for Dermatological Research annual meeting, Copenhagen, Denmark
2013 European COST Network Skin Barrier in Atopic Dermatitis (SkinBAD) final meeting, Copenhagen, Denmark
2013 American Academy of Allergy Asthma and Immunology annual meeting, San Antonio, Texas, USA
2013 British Association of Dermatologists’ annual meeting, Liverpool, UK
2012 European Skin Barrier Research Networks meeting: COST SkinBAD and E2BRN, Venice, Italy
2012 American Academy of Allergy Asthma and Immunology annual meeting, Orlando, Florida, USA
2010 European Academy of Dermatology and Venereology Spring Symposium (President's Forum) Cavtat, Croatia
Sara has led the development of an Art-Science public engagement project entitled ‘Atopic Art: Expressions of Eczema’ in collaboration with Eczema Outreach Scotland, ASCUS Art & Science and two Scottish artists: Josie Vallely and Trevor Gordon.
Work has been displayed at the Dundee Science Festival (2015) and Edinburgh International Science Festival (2016).
The Atopic Art project combines fun and interactive family art events to raise awareness of the impact of atopic eczema on patients and their families.
More details here:
Sara co-authored an Impact Case Study on filaggrin for REF 2014, which was awarded the highest possible mark, contributing to the University of Dundee being ranked joint first in the UK for Impact in Clinical Medicine.
The impact case study can be viewed here.
Sara’s work on peanut allergy research received very extensive media coverage worldwide for example:
Ideas Galore - Peanut Allergy Sufferers Have A Filaggrin Defect?
The Scotsman - Dundee scientists link peanut allergy to rogue gene in skin
Carolina Parent - Peanut allergy linked to genes
Sara is a medical advisor for the patient support groups
Eczema Outreach Scotland:
Ichthyosis Support Group: http://www.ichthyosis.org.uk/
Sara was an advisor for the Wellcome Trust ‘Big Picture’ open access resources on the Immune System: http://bigpictureeducation.com/immune