Deciphering the pathogenic immune infiltrate in atopic dermatitis subtypes

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

Amount: DKK 3,447,335

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.

Switching on melanogenesis: characterization of a yet undiscovered player in melanin production

Grantee: Marta Giacomello, Assistant Professor, University of Padua, Padua, Italy

Amount: DKK 3,990,000

The aim of this project is to further investigate the pathways leading to the production of melanin, a biological molecule that determines skin pigmentation and is responsible for skin color. The complex process for melanin biosynthesis, named melanogenesis, is not yet fully understood. Dysfunctional production of melanin reduces the protection of the skin from ultraviolet light and causes severe dermatological conditions like albinism and vitiligo.   

In preliminary studies, Marta Giacomello has found that the pro-apoptotic protein AIFM3 is likely to be pivotal for melanogenesis. AIFM3 controls the crosstalk among two cell structures: the ‘endoplasmic reticulum’ (important in the synthesis, folding, modification, and transport of proteins), and ‘mitochondria’ (the ‘motors’ that generate most of the chemical energy needed to power the cell’s biochemical reactions).   

Marta Giacomello’s research group will investigate this protein by analyzing its structure and function, its role in intracellular signaling cascades, its physical positioning within the cell and its role in melanogenesis.  

As AIFM3 is very poorly studied (~10 publications), the project will provide unprecedented insight into its role in determining skin pigmentation. 

Regeneration of new fat cells in skin wounds from epigenetically plastic myofibroblasts

Grantee: Maksim Plikus, Professor, University of California – Irvine, CA, USA

Amount: DKK 3,923,850

Summary available soon.

Investigating the developmental basis for anatomical variations in wound repair and disease susceptibility

Grantee: Tanya Shaw, Senior Lecturer, King's College London, UK

Amount: DKK 2,498,527

The aim of this project is to investigate why skin in the facial region heals faster and often with less scarring than the rest of the body but are still prone for other fibrotic diseases like keloid scars. 

Tanya Shaw hypothesizes that this is due to the dermal cells of the face being of a different origin than cells at other sites of the body. Dermal cells of the face stem from so-called neural crest cells and these cells are known for their fast migration and capacity to develop into a multitude of differentiated cells.   

The approach of the project will be to:  

  1. investigate the genetics and epigenetics of keloid scars to determine to what extent they originate from neural crest cells  
  2. compare neural crest cell-derived fibroblasts to fibroblasts from other origins in term of plasticity and cell migration  
  3. manipulate the neural crest cell features in a mouse wound model to investigate if they are critical for wound healing and scarring.   

If the hypothesis can be confirmed, the project holds a strong promise for improvement of wound healing and scarring.