Probiotics targeting Staphylococcus aureus toxin production in atopic dermatitis

Grantee: Hanne Ingmer, Professor, University of Copenhagen

Amount: DKK 2,681,665

Grant category: Research grants in open competition

Year: 2020

Geography: Denmark

Patients with atopic dermatitis (AD) are often colonized by the bacterial pathogen, Staphylococcus aureus (S. Aureus). S. aureus produces a large variety of toxins that contribute to the severity of AD and expression of these toxins is controlled by a cell-cell communication process called “quorum sensing”.  

Professor Ingmer and her team has previously demonstrated that some bacteria produce signaling molecules, which in S. aureus abolish toxin production through repression of quorum sensing and preliminary analyses indicate that probiotic bacteria also belong to this group. 

Thus, the goal of this project is to deliver results addressing the efficacy of probiotics. The project proposes that probiotic bacteria can reduce S. aureus toxin production and that some of the reported benefits of probiotics in AD may be associated with such activity. 

Professor Ingmer will address this hypothesis in collaboration with Statens Serum Institut, the LEO Foundation Skin Immunology Research Center, UCPH and Department of Drug Design and Pharmacology, UCPH. 

Understanding the importance of cIAPs as NF-κB molecular switches in psoriasis

Grantee: Vasileios Bekiaris, Associate Professor, Technical University of Denmark

Amount: DKK 2,815,499

Grant category: Research grants in open competition

Year: 2020

Geography: Denmark

Psoriasis is an inflammatory disease characterized by overproduction of tissue-damaging cytokines by immune cells and keratinocytes. Central cytokines in psoriasis are TNF (tumor necrosis factor) and IL-17 (interleukin 17), which are currently approved therapeutic drug targets. To improve current therapies targeted towards TNF and IL-17, it is important to better understand the biology of the two cytokines in relation to psoriasis.  

The goal of this project is to confirm that two enzymes known as cIAPs (cellular inhibitors of apoptosis proteins) play a central role in psoriasis.  

The two cIAPs are believed to modulate the response of the immune system and of keratinocytes to TNF in order to fine-tune IL-17 production. The project will investigate whether lack of the two cIAPs or their pharmacologic inhibition makes the immune response less pathogenic and reduces the pro-inflammatory nature of keratinocytes during psoriasis.  

Systemic effects of atopic dermatitis: Dysregulated immune responses to the intestinal microbiota

Grantee: Jeppe Madura Larsen, Senior Researcher, Technical University of Denmark

Amount: DKK 4,349,062

Grant category: Research grants in open competition

Year: 2020

Geography: Denmark

Atopic Dermatitis (AD) is a common inflammatory skin disease affecting 15% of children and 3-5% of adults. AD is associated with the risk for developing co-morbidities such as other atopic diseases (food allergy, asthma, and rhinitis) and infections. Co-morbidities are believed to occur because of functional changes in the immune system of AD patients, however, it remains unknown how these changes are established. Emerging experimental studies suggest the existence of a skin-gut immune axis, but the role for the gut remains largely unexplored in AD.

The goal of this project is to determine if AD changes the bacterial microbiota composition and function in the gut, alters the intestinal and systemic immune system, and increases the risk for food allergy co-morbidity via oral sensitization. The project hypothesizes that AD drives dysregulated immune responses to the gut microbiota, which in turn changes the immune system giving rise to atopic co-morbidities and risk for infections. In other words, it is envisaged that AD patients become “allergic” to the bacteria present in their intestine – leading to a “persistent allergic reaction” due to continuous presence of bacteria in the intestine.

The project will use a rat model of AD to investigate the hypothesis and perform a human case-control study to support the clinical relevance of the findings. Identification of bacterial drivers of persistent type-2 inflammation could open new avenues for the prevention and treatment of AD and related co-morbidities.

Deciphering the functional role of circular RNAs in psoriasis

Grantee: Lasse Sommer Kristensen, Associate Professor, Department of Biomedicine, Aarhus University

Amount: DKK 2,467,477

Grant category: Research grants in open competition

Year: 2020

Geography: Denmark

This project aims to answer key questions related to a recently discovered new class of biomolecules, called circular RNAs. These RNA molecules appear to have an important role in early immune responses and the project aims to functionally characterize them in psoriasis patients and compare the results with data from healthy controls.

To study the RNA molecules, the project uses a combination of traditional molecular biology approaches and high-throughput technologies such as RNA-sequencing and NanoString technology.

In summary, this project aims to shed light on the distribution and functional relevance of circular RNAs within psoriatic plagues as well as in normal skin and potentially open new avenues for better treatment and management of psoriasis.

Rapid Clinical Assessment of Skin Barrier Function by Corneocytes Nanotexture

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

Amount: DKK 2,824,593

Grant category: Research grants in open competition

Year: 2020

Geography: Denmark

The goal of this project is to develop a clinically applicable imaging method for evaluation of atopic dermatitis (AD) development, progression and impact of therapeutic intervention.

It is known that AD is closely linked to the status of the skin barrier and therefore Edwin En-Te Hwu and his team will utilize a newly developed biomarker for skin barrier function, the Dermal Texture Index. This index is based on the number of circular nano-objects found on corneocytes (skin cells in the outermost part of the epidermis) of the skin by atomic force microscopy (AFM). However, the current analytical setup is both costly and has a limited throughput which makes it less suitable in a clinical setting.

The team has recently developed a new AFM technique and now aims to develop ‘Dermal AFM’, which will allow a ten times higher throughput in a clinically applicable unit. The unit may also help facilitate the understanding of the biology behind the observed corneocyte nanostructures.

The project is a collaboration between Denmark, Netherlands and Taiwan headed by DTU Health Technology.

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