Deciphering the pathogenic immune infiltrate in atopic dermatitis subtypes

Grantee: Patrick Brunner, Associate Professor, Medical University of Vienna

Amount: DKK 3,447,335

Grant category: Research grants in open competition

Year: 2021

Geography: Austria

The aim of this project is to address the challenge that current treatments for atopic dermatitis (AD) only work as long as they are given.  

A subgroup of the so-called tissue-resident memory (Trm) T-cells appears to be absent in healthy controls and in patients, who have outgrown their AD, but is still present at least a year after a successful clinical outcome following treatment with dupilumab.  

Using state-of-the-art single-cell sequencing methods combined with advanced flow cytometry and so-called suction blistering for collecting sample material, the project will characterize the composition of cells and proteins within skin lesions of AD patients. Compared to most other approaches, this multi-omics approach is expected to provide a much more accurate reflection of what is going on in this complex disease which shows considerable heterogeneity from patient to patient.  

The present project is an extension of a project previously supported by the LEO Foundation (LF18098) where Patrick Brunner successfully refined and validated his sample collection methods. The present project may guide future targeted AD treatment approaches in a more personalized and stratified manner and may offer a relatively short way from bench to bedside.

In vivo gene editing for genodermatoses

Grantee: Thomas Kocher, Postdoc, EB House Austria, Salzburg

Amount: DKK 1,389,845

Grant category: Research grants in open competition

Year: 2020

Geography: Austria

Summary available soon.

Characterizing the disease memory in atopic dermatitis

Grantee: Patrick M. Brunner, Medical University of Vienna

Amount: DKK 2,920,541

Grant category: Research grants in open competition

Year: 2018

Geography: Austria

Atopic dermatitis (AD), the most common chronic inflammatory skin disease, typically starts very early in life.

While many patients outgrow their disease, some develop chronic disease for the rest of their lives. Mechanisms responsible, however, are completely unknown, and no biomarker exists that can predict the course of the disease.

Thus, we want to compare skin from young adults that have outgrown their AD, with skin from patients with active disease (namely normal appearing AD under topical glucocorticoid treatment, which can be expected to flare up again after cessation of treatment, thus harbouring a “disease memory”).

Skin from healthy control subjects will serve as baseline comparators. Due to low immune cell numbers in this type of tissue, we want to use in vivo suction blistering of AD patients to obtain (i) skin resident immune cells and (ii) skin proteins. Suction blister fluid will be analysed with low cytometry and single cell RNAseq (for cells) as well as a proteomic multiplex assays (OLINK) for soluble proteins. The blister roof (i.e. the epidermis) will also be harvested, and keratinocytes will be stored in liquid nitrogen for functional experiments.

Results obtained from flow cytometry, single cell RNAseq and proteomic approaches will then be used for such functional in vitro experiments (e.g. co-culturing, skin equivalents, stimulation experiments) in future research projects.

Overall, we hope that the identification of cellular and/or molecular factors influencing the natural course of AD could possibly identify targets for novel therapeutic approaches in AD, that could induce long term remission – or even lead to a cure – of AD.

The LEO Foundation Award 2016 – Silver Award

Grantee: Dr. Thomas Wiesner

Amount: DKK 500,000

Grant category: LEO Foundation Awards

Year: 2016

Geography: Austria

Presented to Dr. Thomas Wiesner. Dr. Wiesner is breaking new ground to find new mechanism-based cancer therapies. Following medical school, Dr. Wiesner wrote his thesis on the genomic aberrations of cutaneous lymphoma and completed his residency in dermatology at the Medical University of Graz in Austria. Dr. Wiesner spent five years conducting basic and translational research using cutting-edge techniques within high-throughput sequencing techniques in particular. His work within skin cancer research resulted in key discoveries, in particular concerning the genomic landscape of skin tumours.

Based on his experience as a physician-scientist and his access to high-quality clinical samples, Dr. Wiesner plans to combine high-throughput sequencing technologies, computational approaches and functional assays in order to define the relevant genomic and epigenomic aberrations in skin cancer and pave the way for new mechanism-based cancer therapies.

Serum transcriptomics in melanoma patients

Grantee: Igor Vujic, MD, Assistant Professor, Sigmund Freud University & Department of Dermatology, Rudolfstiftung Hospital, Vienna

Amount: DKK 265,000

Grant category: Research grants in open competition

Year: 2016

Geography: Austria

The Austrian-American team behind the study, led by Dr. Igor Vujic, aims at identifying more specific and sensitive biomarkers in order to better detect and monitor progression of malignant melanoma – a common and deadly skin cancer that is difficult to treat, and that accounts for numerous deaths each year.

In the clinic, physicians face two main problems around malignant melanoma: detection of early disease, and monitoring of disease progression, recurrence and its response to therapies. The existing melanoma biomarkers are not very specific and only rarely help.

Melanoma cells, however, produce a specific set of RNA molecules of which some are excreted and found in the blood stream – ready for identification and use as biomarkers. Recent technical advances make it possible to extract and analyse serum RNA and identify the cell of origin.

The team will mainly concentrate on non-coding RNAs, a new class of molecules known to be very specific for certain diseases such as cancer. Preliminary studies have identified and confirmed 237 interesting candidates through RNA-Seq TCGA (The Cancer Genome Atlas) data.

In the course of the study, the team will perform RNA-Seq studies on serum samples from melanoma patients and healthy individuals to find differences in RNA quality and quantity to be used as melanoma serum-markers. The team will moreover test changes of the amount of these specific RNA molecules in melanoma patients over time to discover if they can be used as disease progression biomarkers.

The LEO Foundation Award 2012 – Gold Award

Grantee: David Schrama

Amount: DKK 1,000,000

Grant category: LEO Foundation Awards

Year: 2012

Geography: Austria

Presented to Assistant Professor David Schrama at the Dermatology Department at Graz Medical University, Austria.

Schrama’s research focuses on melanoma biology. His research team currently analyses the impact of genetic diversity among patients and tumours on prognosis and clinical outcome of therapies. In recent years, Schrama’s scientific work has focused on unravelling the biology of another skin cancer; the polyomavirus associated merkel cell carcinoma.