Grantee: Edwin En-Te Hwu, Associate Professor, Technical University of Denmark, Kgs. Lyngby, Denmark

Amount: DKK 2,824,593

The severity of atopic dermatitis (AD) is closely correlated to skin barrier.

In recent years, the nanoscale anatomy (nanotexture) on corneocytes surface was explored through atomic force microscopes (AFMs), hinting.

The number of circular nano-objects yielded a biomarker called dermal texture index (DTI). Furthermore, clinical studies revealed that the DTI is closely associated with skin barrier function.

AFMs can measure tape-stripped corneocytes nanotexture without any sample preparations. However, conventional AFMs suffer from low throughput at a high cost and limited usability in a clinical setting.

Recently, we have pioneered a unique AFM technique and we would like to integrate DTI analysis for skin barrier function assessment. This project aims to develop a tailor-made Dermal AFM that has ten times higher throughput than conventional AFMs and is easy to use in clinical environments.

The project is coordinated from DTU Health Technology and is performed in collaboration with hospitals in Denmark, Netherlands and Taiwan for AD severity assessment and skin sample acquisition.

Different regions AD nanotexture data (Europe and Asia) facilitate optimization of DTI to assess AD in a subclinical phase, as well as courses and pharmacotherapy effectiveness quantitatively. The Dermal AFM may also, in future research projects, pave the way for unveiling the science behind the corneocyte nanotexture formation.

Grantee: Andor Pivarcsi, Associate Professor, Karolinska Institutet, Stockholm, Sweden

Amount: DKK 4,164,300

Cutaneous Squamous Cell Carcinoma (cSCC) is the most common and fastest-increasing cancer with metastatic potential, which accounts for 20% of all skin cancer-related deaths.

Patients with advanced tumors lack efficient treatment options, thus, there is an urgent medical need to find novel therapeutic approaches.

Long noncoding RNAs (lncRNAs) represent a crucial but as yet largely unexplored layer of gene regulation. We hypothesize that alterations in lncRNA-networks contribute to malignant progression and the that modulation of lncRNA expression can have therapeutic relevance.

Recently, we have performed a comprehensive RNAseq analysis in cSCC and identified a set of novel lncRNAs with altered expression in cSCC and whose functions are poorly characterized or completely unknown. These lncRNAs represent potential regulators of epidermal homeostasis and carcinogenesis.

In this study, we will explore the function of the identified lncRNAs in loss- and gain-of-function studies using in vitro and in vivo experimental models of cancer and differentiation, in vivo modulation of lncRNA-activity by delivery of antisense oligonucleotides (ASOs).

Additionally, we will identify the pathways regulated by cSCC-associated lncRNAs and define their mechanism of action by the biochemical characterization of binding partners.

Results of the proposed project will reveal the role of lncRNAs in epidermal carcinogenesis and pave the way towards the use of ASO-based be therapy of skin cancer.