Research Group Ning Xu Landén

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Research focus

Regulatory RNAs, skin wound healing, psoriasis

Introduction

Both chronic non-healing wounds and psoriasis are major and rising health and economic burdens worldwide and lack of effective treatment. Investigation of the role of regulatory RNAs, for example microRNA and long non-coding RNAs, represents an emerging concept, and constitutes a promising area for pharmaceutical intervention. The goal of our laboratory is to unravel the role(s) of regulatory RNAs in skin wound healing and in psoriasis. Moreover, we aim to translate basic scientific findings into therapeutic interventions for patients.

Major research focus

Project  1. The role of non-coding RNAs in human skin wound healing

The goal of our research is to develop novel RNA-based treatments to improve healing of human skin wounds. The immense economic and social impact of deficient wound healing e.g. chronic ulcers post-surgical wounds care and skin scarring, calls for attention and allocation of resources to understand biological mechanisms underlying wound complications. Due to the complex nature of wounds, efficient targeted approach to enhance healing are essentially lacking today.

The recent discovery of non-coding RNAs (ncRNAs) as powerful gene regulators provides hope to develop novel RNA-based treatments for a wide variety of diseases. However, the role of ncRNAs in human skin wound healing remains largely unexplored.

The objective of our study is to reveal the role(s) of ncRNAs in skin wound healing and to explore the potential of RNA-based therapy for chronic wounds. We primarily focus on small ncRNAs, i.e. microRNAs (miRNAs) and long-non-coding RNAs (lncRNAs) and study:

(i) The expression profiles of miRNA/lncRNA in injured human skin;

(ii) The biological function of differentially expressed miRNAs/lncRNAs in wounds;

(iii) The molecular mechanisms mediating the biological functions of wound related miRNAs/lncRNAs;

(iv) The therapeutic potentials of targeting wound related miRNAs.

Our research network is composed of both clinicians and scientists, which allows us to perform ‘Bench-to-Bedside’ research. At present, we are investigating the novel roles of miRNAs and lncRNAs in skin wounds using our unique collection of human wound tissues. In the next step, we aim to translate our basic scientific findings into therapeutic interventions for wound patients.

https://vimeo.com/149126472

Ragnar Söderberg Fellow in Medicine 2015

 

Project  2. Investigation of the mechanistic links between psoriasis and co-morbidities

Psoriasis is an immune-mediated inflammatory disease of the skin. It is a lifelong disease with spontaneous remissions and exacerbations, affecting the patients’ life quality substantially, and there is no cure for it today. Epidemiological studies show that psoriasis patients have increased risks of developing systemic co-morbidities, e.g. obesity, overt diabetes and cardiovascular disease; however, the molecular mechanisms behind these co-morbidities remain unexplored. We have previously demonstrated that miRNAs play important roles in skin inflammation of psoriasis. Here, we study whether miRNA could also be a key mechanistic link between psoriasis and its co-morbidities, using materials from a large biobank of psoriasis patients in Stockholm. This study will further increase our understanding about pathogenesis of psoriasis. It is essential for the effective management of psoriasis and prevention of its related co-morbidities.

https://vimeo.com/195280801

Interplay of skin and fat in psoriasis / Samspel mellan hud och fett i psoriasis

Team members

Ning Xu Landén, Associate Professor, Group leader

Dongqing Li, PhD, Postdoc fellow

Eva Herter, PhD, Postdoc fellow

Jianmin Wu, PhD, Visiting researcher

Xi Li, MD, PhD student

Maria-Alexandra Toma, PhD Student

External Links

www.xulandenlab.com

Recent key publications

MicroRNA-132 promotes fibroblast migration via regulating RAS p21 protein activator 1 in skin wound healing.
Li X, Li D, Wikstrom J, Pivarcsi A, Sonkoly E, Ståhle M, et al
Sci Rep 2017 Aug;7(1):7797

MicroRNA-132 with Therapeutic Potential in Chronic Wounds.
Li X, Li D, Wang A, Chu T, Lohcharoenkal W, Zheng X, et al
J. Invest. Dermatol. 2017 Aug;():

MicroRNAs in skin wound healing.
Li D, Landén N
Eur J Dermatol 2017 Jun;27(S1):12-14

Non-Coding RNAs: New Players in Skin Wound Healing.
Herter E, Xu Landén N
Adv Wound Care (New Rochelle) 2017 Mar;6(3):93-107

Psoriasis Skin Inflammation-Induced microRNA-26b Targets NCEH1 in Underlying Subcutaneous Adipose Tissue.
Cheung L, Fisher R, Kuzmina N, Li D, Li X, Werngren O, et al
J. Invest. Dermatol. 2016 Mar;136(3):640-8

Transition from inflammation to proliferation: a critical step during wound healing.
Landén N, Li D, Ståhle M
Cell. Mol. Life Sci. 2016 Oct;73(20):3861-85

MicroRNA-132 enhances transition from inflammation to proliferation during wound healing.
Li D, Wang A, Liu X, Meisgen F, Grünler J, Botusan I, et al
J. Clin. Invest. 2015 Aug;125(8):3008-26

MicroRNA-31 Promotes Skin Wound Healing by Enhancing Keratinocyte Proliferation and Migration.
Li D, Li X, Wang A, Meisgen F, Pivarcsi A, Sonkoly E, et al
J. Invest. Dermatol. 2015 Jun;135(6):1676-1685

MicroRNA-31 is overexpressed in psoriasis and modulates inflammatory cytokine and chemokine production in keratinocytes via targeting serine/threonine kinase 40.
Xu N, Meisgen F, Butler L, Han G, Wang X, Söderberg-Nauclér C, et al
J. Immunol. 2013 Jan;190(2):678-88

MiR-125b, a microRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2.
Xu N, Brodin P, Wei T, Meisgen F, Eidsmo L, Nagy N, et al
J. Invest. Dermatol. 2011 Jul;131(7):1521-9