Curing Cutaneous Calcinosis (CUCUC)

Grantee: Beate Lichtenberger, Principal Investigator, Medical University of Vienna

Amount: DKK 2,757,196

Grant category: Serendipity Grants

Year: 2023

Geography: Austria

Beate Lichtenberger investigates the mechanisms behind cutaneous calcinosis caused by over-activation of Hedgehog signaling in the dermis to improve treatment options.

Cutaneous calcinosis (CUC) is a debilitating condition characterized by the abnormal deposition of calcium salts in the skin and subcutaneous tissues, leading to pain, impaired mobility, and disfigurement. Despite its significant impact on patient quality of life, effective therapeutic interventions for CUC remain lacking, and there is no model system to study the disease. Beate Lichtenberger and her team serendipitously discovered that over-activation of Hedgehog (Hh) signaling in dermal fibroblasts leads to calcium precipitates and inflammation in limb and tail skin of mice, recapitulating the human disease

Beate Lichtenberger will elucidate the underlying mechanisms driving calcium deposition, inflammation, and tissue damage in cutaneous calcinosis. Furthermore, she will perform single cell RNA sequencing (scRNA-Seq) of human CUC tissue to assess which cell types apart from fibroblasts contribute to the pathogenesis and how

By advancing the understanding of the pathogenesis of CUC and developing targeted therapeutic strategies like repurposing of existing Hh inhibitors, Beate Lichtenberger’s project has the potential to revolutionize the treatment landscape and significantly improve the lives of individuals afflicted by this condition.

Skin barrier immune defence against the multidrug-resistant fungal pathogen Candida auris

Grantee: Adelheid Elbe-Bürger, Associate Professor, Medical University of Vienna

Amount: DKK 3,139,984

Grant category: Research Grants in open competition

Year: 2023

Geography: Austria

Adelheid Elbe-Bürger’s project investigates the pathogen:host interplay using ex-vivo skin models in relation to infections by Candida auris – a multidrug resistant fungus.

Drug-resistant microorganisms represent a serious human health threat worldwide. Candida auris (C. auris) is an emerging, multidrug-resistant human fungal pathogen. Its pronounced skin tropism (i.e., ability to infect) promotes persistent colonization of the skin and facilitates skin-skin transmission within health care facilities, leading to life-threatening infections of high mortality in immunocompromised patients.

The lack of clinically relevant primary human skin models with a disrupted barrier function has been a serious impediment to better understand the C. auris:host interplay during pathogenesis.

To counter this, Adelheid Elbe-Bürger and her team have developed unique, standardized human ex vivo skin models that allow them to study C. auris colonization and penetration as well as identify the immune cells that orchestrate both the recognition and immune defense against this fungus.

In Adelheid Elbe-Bürger’s project infected skin biopsies will be analyzed by single-cell RNA-sequencing, flow cytometry as well as confocal microscopy. Culture supernatants will be subjected to multiplex proteomics (i.e., a way to analyze many proteins simultaneously) to decipher host components governing fungal:host interactions.

The overarching aim is that the results will advance the understanding of tissue-specific mechanisms of anti-C. auris defense and may help to pave the way for improved therapeutic options.

Unravelling the Link Between Past Infections, the Microbiome, and Therapy Resistant Psoriasis

Grantee: Johannes Griss, MD PhD, Medical University of Vienna

Amount: DKK 3,975,754

Grant category: Research Grants in open competition

Year: 2023

Geography: Austria

Johannes Griss’ project aims to elucidate the immunological memory of biologics-resistant psoriasis patients using advanced screening methodology. This, coupled with identifying immune composition in lesions, may reveal new treatment options.

Efficient treatment of cutaneous psoriasis is an example of the great success of modern biologicals. Nevertheless, a subset of patients remain that do not respond to most biologic treatments. This group remains in high need of efficient treatment options. It has been speculated that therapy-resistant psoriasis is caused by either specific compositions of the microbiome or unique previous viral infections.

Viral infections can trigger autoimmune diseases and dysregulated immune responses against the microbiome may trigger inflammatory and autoimmune diseases. However, to date it has not been possible to cover the vast space of antigens represented by the microbiome. Johannes Griss and his team recently showed that phage display libraries (PhIP-Seq, a high-troughput screening method utilizing bacteria-infecting viruses) can be used to identify and characterize antibodies against several 100,000s of antigens simultaneously instead of several 100s with conventional methods. This method can reveal both previous viral infections as well as the composition of the microbiome at large scale and low cost.

In this project, the team will use their novel PhIP-seq approach to characterize the immunologic state of a large in-house cohort of psoriasis patients. They will pair this with an in-depth characterization of the lesional immune composition. In this way, they aim to be able to test whether a patient’s immune memory alters psoriatic inflammation and influences therapy response.

If successful, their findings may reveal novel treatment approaches and biomarkers to allow optimal matching of biologic treatments.