ENIKÖ SONKOLY

Exploring the role and therapeutic potential of non-coding RNAs in chronic skin inflammation

About

Skin is our largest organ, representing an interface between the organism and the environment. The uppermost part of the skin, the epidermis is a continuously renewing tissue governed by a tightly regulated differentiation program. Being much more than just a physical barrier, the epidermis is a complex immunological barrier that can recognize and respond to external stimuli including pathogens.

Psoriasis and atopic dermatitis are the most common chronic inflammatory skin diseases, and they have a significant impact on the quality of life of the affected patients. In these chronic inflammatory skin diseases, activation of the immune system in interaction with keratinocytes, the main cell type in the epidermis, sustains chronic inflammation.

Non-coding RNAs, constituting a large part of transcriptional output in our cells, have important regulatory functions in the cells. Both short (e.g. miRNAs) and long (long non-coding RNAs, lncRNAs) have emerged as important gene regulators in health and disease.

 

Our research

Our research aims to explore how non-coding RNAs contribute to chronic inflammatory skin diseases, and their potential as biomarkers and therapy targets. For this, we use patient samples, cell culture, 3D epidermal models and animal models of skin inflammation. We have identified several miRNAs that regulate crucial cellular functions in psoriasis and their modulation affects skin inflammation in preclinical models.

Exploring the function of non-coding RNAs in skin diseases also sheds light on their functions in the complex regulatory networks that ensure proper epidermal differentiation and immune responses but prevent excessive inflammation in normal skin.

 

Grant support

National Psoriasis Foundation (USA), Discovery Grant, 75000 USD, 2019-2021 

ALF Medicine Project Grant, 1.500.000 SEK, 2019-2021

KID Grant, 50% support for a PhD student 2021- (to be recruited)

Swedish Research Council, Half-time Position in Clinical Research Environment, 1 850 000 SEK/ year 2016-2018

ALF Medicine project grant, 929 000 SEK, 2016-2017

KID grant for Ankit Srivastava (2014-2018) and Lorenzo Pasquali (2016-2020)

Åke Wibergs Foundation, 300 000 SEK, 2015

Inflammation Europe ASPIRE 2014 research award (Pfizer), 515 221 SEK, 2015

The Swedish Skin Foundation, 800 000 SEK, 2015-2016

Psoriasisförbundet, 150 000 kr, 2015-2016

KI Research Foundation, 27 600 SEK, 2014-2015

Psoriasisförbundet, 150 000 SEK, 2013

National Psoriasis Foundation (USA),  200 000 USD, 2012-2014

 

Selected publications

Pasquali L,  Svedbom A,  Srivastava A,  Rosén E,  Lindqvist U,  Ståhle M,  Pivarcsi A,  Sonkoly E. Circulating microRNAs in extracellular vesicles as potential biomarkers for psoriatic arthritis in patients with psoriasisJ Eur Acad Dermatol 2020 34;6 1248-1256

Srivastava A,  Meisgen F,  Pasquali L,  Munkhammar S,  Xia P,  Stahle M,  Landen NX,  Pivarcsi A,  Sonkoly E. Next-Generation Sequencing Identifies the Keratinocyte-Specific miRNA Signature of Psoriasis. J Invest Dermatol 2019 139;12 2547-2550.e12

Pasquali L,  Srivastava A,  Meisgen F,  Das Mahapatra K,  Xia P,  Xu Landén N,  Pivarcsi A,  Sonkoly E. The Keratinocyte Transcriptome in Psoriasis: Pathways Related to Immune Responses, Cell Cycle and Keratinization. Acta derm vener 2019 99;2 196-205

Srivastava A,  Ståhle M,  Pivarcsi A,  Sonkoly E. Tofacitinib Represses the Janus Kinase-Signal Transducer and Activators of Transcription Signalling Pathway in KeratinocytesActa derm vener 2018 98;8 772-775

Srivastava A, Nikamo P, Lohcharoenkal W, Li D, Meisgen F, Xu Landén N, Ståhle M, Pivarcsi A, Sonkoly E. MicroRNA-146a suppresses IL-17-mediated skin inflammation and is genetically associated with psoriasis. J Allergy Clin Immunol. 2017 Feb;139(2):550-561.

Meisgen F, Xu Landén N, Wang A, Réthi B, Bouez C, Zuccolo M, Gueniche A, Ståhle M, Sonkoly E, Breton L, Pivarcsi A. MiR-146a negatively regulates TLR2-induced inflammatory responses in keratinocytes. J Invest Dermatol. 2014 Jul;134(7):1931-1940.

Meisgen F, Xu Landén N, Bouez C, Zuccolo M, Gueniche A, Ståhle M, Sonkoly E, Breton L, Pivarcsi A. Activation of Toll-like receptors alters the microRNA expression profile of keratinocytes. Exp Dermatol. 2014 Apr;23(4):281-3.

Pivarcsi A, Meisgen F, Xu N, Ståhle M, Sonkoly E. Changes in the level of serum microRNAs in psoriasis patients after anti-tumor necrosis factor-α therapy. Br J Dermatol. 2013 Sep;169(3):563-70.

Xu N, Meisgen F, Butler LM, Han G, Wang XJ, Söderberg-Nauclér C, Ståhle M, Pivarcsi A, Sonkoly E. MicroRNA-31 is overexpressed in psoriasis and modulates inflammatory cytokine and chemokine production in keratinocytes via targeting STK40. J Immunol. 2013 Jan 15;190(2):678-88.

Meisgen F, Xu N, Wei T, Janson PC, Obad S, Broom O, Nagy N, Kauppinen S, Kemény L, Ståhle M, Pivarcsi A, Sonkoly E. MiR-21 is up-regulated in psoriasis and suppresses T cell apoptosis. Exp Dermatol. 2012 Apr;21(4):312-4.

Wei T, Orfanidis K, Xu N, Janson P, Ståhle M, Pivarcsi A and Sonkoly E. The expression of microRNA-203 during human skin morphogenesis. Exp. Dermatol. 2010 Sep;19(9):854-6

Sonkoly E, Janson P, Majuri M, Savinko T, Fyhrquist N, Xu N, Wei T, Stenvang J, Kauppinen S, Alenius H, Lauerma A, Homey B, Winqvist O, Ståhle M, Pivarcsi A. MiR-155 is overexpressed in atopic dermatitis and modulates T cell proliferative responses by targeting CTLA-4. J All Clin Immunol. 2010 Sep;126(3):581-9.e1-20.

Sonkoly E, Wei T, Pavez Loriè E, Suzuki H, Kato M, Törmä H, Ståhle M, Pivarcsi A. Protein kinase C-dependent upregulation of miR-203 induces the differentiation of human keratinocytes. J Invest Dermatol. 2010 Jan;130(1):124-34.

E Sonkoly, T Wei, PC Janson, A Saaf, L Lundeberg, M Tengvall-Linder, G Norstedt, H Alenius, B Homey, A Scheynius, M Stahle, A Pivarcsi. MicroRNAs: novel regulators involved in the pathogenesis of Psoriasis? PLoS ONE. 2007 Jul 11;2(7):e610.