Projects

Psoriasis and atopic dermatitis

(PI: Enikö Sonkoly)

Psoriasis and atopic dermatitis are the most common chronic inflammatory skin diseases. A combination of genetic and environmental factors contributes to the development of these diseases, which share superficial similarities however their immunopathogenesis is distinct.

Psoriasis is characterized by a vicious circle of inflammation in the skin fueled by disturbed interactions between keratinocytes (skin’s epithelial cells) and infiltrating immune cells. Psoriasis is a prime example for the translational revolution in dermatology: our increasing knowledge on the immunopathogenesis has led to the development of new, efficient targeted therapies. Nevertheless, the regulatory mechanisms involved are far from fully known and there is a need for new efficient topical and systemic treatments. We have previously shown that non-protein-coding RNAs (miRNAs and lncRNAs), which are important regulators of gene expression, can contribute to biological processes relevant to the pathogenesis and that their modulation is beneficial in preclinical models.

Atopic dermatitis is characterized by dry skin and intense itch as well as inflammatory lesions arising from a combination of skin barrier deficiency, dysbiosis and mainly Th2-type inflammation in the skin. Better understanding of the interplay between these factors is a prerequisite to develop novel treatments. Our work has shown that ncRNAs are dysregulated in atopic dermatitis skin; however, their roles are still largely unexplored.

Using a combination of patient samples, animal models, cell culture and 3D epidermal models (Figure 1), our group investigates the following research questions:

  1. Which regulatory non-coding RNAs are dysregulated in chronic inflammatory skin diseases and in which cells?
  2. Which biologic processes, genes and signaling pathways are regulated by the disease-associated non-coding RNAs in the skin? What is the biological function of the disease-associated non-coding RNAs? What is their mechanism of action?
  3. Can therapeutic modulation of non-coding RNAs be beneficial in chronic inflammatory skin diseases?

How is the cell-specific coding and non-coding RNA signature in psoriasis epidermis? Which cells interact closely with each other and how are their transcriptional signatures?

Figure 1.

Skin barrier and genetic skin diseases

(PI: Enikö Sonkoly and Andor Pivarcsi)

We are investigating the genetic and epigenetic regulation of epidermal development and the skin barrier. A functional skin barrier is essential to protect us from water loss, infections, chemicals and other environmental factors. Genetic disorders such as ichthyosis and other inherited skin diseases are characterized by impaired skin barrier function have a substantial negative effect on the affected individuals and their families’ lives. We investigate the molecular events during skin barrier formation in 3D skin models (Figure 2 showing successive formation of the skin barrier in this model) and the pathogenesis of genetic skin diseases (genodermatoses) including the role and therapeutic potential of regulatory RNAs in the process in a translational setting as a collaboration between the university hospital and academic research labs using patient-derived cells and lab-grown skin models.

We are also part of an EU COST action NETSKINMODELS (European Network for Skin Engineering and Modeling, A21108, netskinmodels.com), driving the development of cell-based skin models for dermatological research.

Keratinocyte cancers and skin ageing

(PI: Andor Pivarcsi)

Both long non-coding RNAs (lncRNA) and microRNAs (miRNAs) have been implicated in organismal development, tissue differentiation and ageing, with potential to transform our understanding of disease mechanisms and clinical practices. Our research focuses on the understanding of the role of non-coding RNAs in skin ageing and keratinocyte-cancers, with focus on cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the most common human cancer with metastatic potential. Although most cSCCs can be fully cured with surgical excision, a subset of cSCC is metastatic and associated with poor prognosis. Our overarching aim is to understand the role of non-coding RNAs, important regulators of cell differentiation and organ development, in the pathogenesis of the disease (Figure 3). Via the systematic molecular analysis of patient-derived samples from tumors and precancerous lesions, and in vitro and in vivo cancer models, we aim to understand their role in the development and progression of the disease. We have recently identified a set of highly skin-specific non-coding RNAs, whose functions are unknown and may hold the key to the understanding of skin development. We also investigate the function and mode of action of cSCC-associated non-coding RNAs. We are currently also studying the role of non-coding RNAs with putative oncogenic function in the disease. In addition to cSCC, we have an interest in the molecular background of another keratinocyte-derived cancer, basal cell carcinoma (BCC). Better understanding of the function of keratinocyte cancer-associated non-coding RNAs will lay the foundations of future work using them as therapeutic targets by novel RNA-based therapeutics.

Figure showing keratinocyte cancers and skin ageing.
Figure 3.

Hidradenitis suppurativa

(PI: Enikö Sonkoly)

Hidradenitis suppurativa is a common inflammatory skin disease characterized by recurrent painful inflamed lesions in the skin folds. The disease has a profound negative impact on the quality of life of affected patients, due to the pain, secretions, and the chronic nature of the disease. In collaboration with other dermatology clinics in Sweden, we are establishing a research registry and an associated biobank of tissue and blood samples to follow up the disease course, disease severity, treatments, quality of life, inflammatory markers and associated diseases. We aim to investigate which factors determine patients’ quality of life, how different treatments affect distinct symptoms and the potential association with gastrointestinal symptoms and diseases.

Last modified: 2023-05-23