Research group Maria Bradley

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Senior lecturer/senior physician

Maria Bradley

Organizational unit: Research Group M Bradley
E-mail: Maria.Bradley@ki.se

Associate Professor and Senior Consultant at Department of Dermatology , Karolinska University Hospital

Senior Lecturer and Head of Dermatology Unit, Department of Medicine Solna, Karolinska Institutet

Associate Professor and Senior Consultant at Department of Dermatology , Karolinska University Hospital

Senior Lecturer and Head of Dermatology Unit, Department of Medicine Solna, Karolinska Institutet

Group members

Samina Asad, postdoc

Agne Lieden, postdoc

Kassahun Desaleign, associated

Lina Ivert, associated

Mårten Winge, postdoc

Hedvig Glans, PhD student ,Anna Bergman PhD student

Carl-Fredrik Wahlgren, Professor/senior physician 

Emma Johansson, PhD student

Maria Karlsson, associated

Main Project

Atopic dermatitis (AD) is an inflammatory skin disorder.  The pathogenesis is a complex interaction between environmental factors and genetic predisposition, The overall aim is to improve the understanding of the development of atopic dermatitis (AD) by genetic and functional studies of AD with a focus on skin barrier defects.

We have several projects ongoing in this field. We have used  a large family material with 500 families where at least two siblings had AD, and characterised them phenotypically.

We did a screening of sibling pairs and identified 5 chromosome areas linked to atopic dermatitis and allergic rhinoconjunctivitis. Since these chromosome areas contain numerous of genes we wished to further narrow the area, and used microarrays to demonstrate a number of genes that were up- or down-regulated in the chromosome areas earlier described. Using this combination technique we identified that SOCS3 is one of the susceptibility genes underlying atopic dermatitis.

 A Scottish group have identified a gene (filaggrin) which is important for the skin barrier and of major significance for the development of atopic dermatitis. We could confirm their findings in our family material but filaggrin has proven to be a population-specific gene with different mutations in different populations. In collaboration with Ethiopian colleagues we investigated the prevalence of filaggrin mutations among Ethiopia AD patients where we could not demonstrate any link with atopic dermatit in that population. This was the first African population to be investigated with reference to filaggrin. We have then continued to explore the filaggrin gene and it’s contribution to atopic dermatitis in different populations in collaborations with researchers from different parts of the world.

We have also used exome sequencing in order do identify other skin barrier genes contributing to atopic dermatitis. Right now together with collaborators fron ScieLife we use an method called “high throughput chromosome conformation and sequence capture (HiCap)” in order to elucidate novel genome-wide regulatory elements that play key role in gene control and expression in keratinocytes and to identify genetic variations in these regions that completely disrupt or alter the genome regulation and gene expression in a specific cell line and between atopic dermatitis patients from different populations and healthy controls.

So in summary we have used different genetic approaches in patient material from different parts of the world in order to better understand the gentic background of atopic dermatitis among Swedish atopic dermatitis patients as well as patients from other populations.

Selected publications

Susceptibility loci for atopic dermatitis on chromosomes 3, 13, 15, 17 and 18 in a Swedish population.
Bradley M, Söderhäll C, Luthman H, Wahlgren C, Kockum I, Nordenskjöld M
Hum. Mol. Genet. 2002 Jun;11(13):1539-48

 

Elevated expression and genetic association links the SOCS3 gene to atopic dermatitis.
Ekelund E, Saaf A, Tengvall-Linder M, Melen E, Link J, Barker J, et al
Am. J. Hum. Genet. 2006 Jun;78(6):1060-5

Global expression profiling in atopic eczema reveals reciprocal expression of inflammatory and lipid genes.
Sääf A, Tengvall-Linder M, Chang H, Adler A, Wahlgren C, Scheynius A, et al
PLoS ONE 2008 ;3(12):e4017

Novel filaggrin mutation but no other loss-of-function variants found in Ethiopian patients with atopic dermatitis.
Winge M, Bilcha K, Liedén A, Shibeshi D, Sandilands A, Wahlgren C, et al
Br. J. Dermatol. 2011 Nov;165(5):1074-80

Whole-exome sequencing of Ethiopian patients with ichthyosis vulgaris and atopic dermatitis.
Taylan F, Nilsson D, Asad S, Lieden A, Wahlgren C, Winge M, et al
J. Allergy Clin. Immunol. 2015 Aug;136(2):507-9.e19

Winge MCC, Ohyama B, Dey C, Boxer L, Wei Li W, Ehsani-Chimeh N,  Truong A, Wu D, Armstrong A, Makino T, Davidson M, Starcevic D, Nguyen N, Hashimoto T, Bernard Homey B,  Khavari P, Bradley M, Waterman E Marinkovich P.

A Central Role For Epidermal Rac1 Activation In Human Psoriasis

J Clin Invest. 2016 Jul 1;126(7):2661-77. doi: 10.1172/JCI85738

CONTACT

Senior lecturer/senior physician

Maria Bradley

Organizational unit: Research Group M Bradley
E-mail: Maria.Bradley@ki.se