Andor Pivarsci research group

PI: Professor Andor Pivarcsi

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 tumours 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. Our main research focus currently is the understanding of the role of long non-coding RNAs (lncRNAs) in one of the most common human cancers, squamous cell carcinoma of the skin (cSCC). Our results have identified important roles for ncRNAs in skin development, tissue differentiation and ageing, in the emergence and progression of cancer. We have also 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.

The group uses patient material to identify novel disease-relevant non-coding RNAs by transcriptomic analyses. Moreover, CRISPR-Cas9-based loss-of-function and gain-of-function experiments in cell culture models, 3D reconstructed tissue equivalents and mouse disease models are used to identify the exact molecular role of disease-relevant ncRNAs, as well as, to an increasing extent, data analysis with bioinformatics methods.

PI: Professor Enikö Sonkoly

Psoriasis and atopic dermatitis are the most common chronic inflammatory skin diseases. The Sonkoly-group is studying the molecular background of these diseases, and showed for the first time in 2007 the involvement of miRNAs, short non-coding regulatory RNAs, in psoriasis and atopic dermatitis. Subsequent studies from the group have demonstrated important regulatory roles for specific miRNAs as well as long non-coding RNAs in inflammatory responses in the skin and regulating the balance of epidermal proliferation/differentiation. The group uses a combination of patient samples, animal models, cell culture and 3D epidermal models, to address 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?

In addition, current investigations aim to create an atlas of the cell-specific coding and non-coding RNA signature in psoriasis epidermis, and identify cells that interact closely with each other within the epidermal compartment in psoriasis skin lesions.

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.

The group is part of an EU COST action network (NETSKINMODELS; European Network for Skin Engineering and Modeling, A21108, netskinmodels.com), driving the development of cell-based skin models for dermatological research.