Developing 1600 nm OCT angiography to quantify severe inflammatory epidermal hyperplasia in atopic dermatitis

Grantee: Stephen Matcher, Professor, University of Sheffield

Amount: DKK 4,197,519

Grant category: Research grants in open competition

Year: 2021

Geography: United Kingdom

The aim of this project is to enable quantification of the effects of treating atopic dermatitis (AD) with new therapies. New therapies have similar effectiveness to steroids but are much more expensive. Thus, there is a need for demonstrated benefits and better long-term safety to persuade healthcare providers to fund them.

Optical coherence tomography (OCT) is an ideal tool to quantify the benefits of new drugs for treating AD, whilst checking that they do not cause skin thinning, which is a risk with long-term use of steroids. OCT is a non-invasive imaging technique that uses laser light to provide ultrasound-like images with higher resolution – and OCT avoids the need to perform painful biopsies.

One problem with the current OCT systems is that if the skin inflammation becomes too high, it becomes difficult to quantify because OCT can only image to depths of around 1 mm. This limited depth penetration can potentially be improved by using a longer wavelength of laser light. With the project, Stephen Matcher will quantify the improvement in OCT image quality when using 1600 nm light rather than the current 1300 nm light.

If successful, the project holds a strong potential for use in both clinical trials and clinical practice with a highly needed more patient-friendly tool for measuring drug efficacy in skin diseases such as atopic dermatitis.

Immunomodulatory porous biomaterials for skin regeneration

Grantee: Philip Scumpia, Assistant Professor, University of California – Los Angeles, CA

Amount: DKK 3,885,333

Grant category: Research grants in open competition

Year: 2021

Geography: USA

This project predicts in situ/local immunomodulatory biomaterials as a novel therapeutic approach to engineer regenerative wound healing and limit scarring.

Local tissue engineering represents a promising approach to regenerate tissue, however, immunologic barriers to restore tissue strength and function must be overcome. In previous studies, Philip Scumpia has shown that by simply inducing an adaptive immune response from a novel synthetic biomaterial that mimics the natural porosity and other characteristics of the skin, it is possible to provide the inductive signals to regenerate hair follicles and sebaceous glands in small murine cutaneous wounds.

In this project, it is proposed to identify the cells and the signals from the innate and adaptive immune system responsible for switching profibrotic signals in the wound environment to regenerative signals. This will be achieved by combining novel, pro-regenerative biomaterial formulations with loss-of-function studies of cells and factors of the immune system. Single-cell RNA-sequencing, multiplexed immunofluorescent microscopy, and bioinformatics analyses will be applied to directly assess biomaterial-to-cell and cell-to-cell interactions at the molecular level.

If successful, the project may help identify key players in regenerative wound healing, which would be of great importance.

Sodium intake and storage in the skin

Grantee: Katrina Abuabara, Associate Professor, University of California – San Francisco, CA

Amount: DKK 3,965,534

Grant category: Research grants in open competition

Year: 2021

Geography: USA

The rapid increase in prevalence of AD suggests that environmental factors play an important role, but which environmental drivers are most important and the mechanism by which they impact AD is unclear. Large epidemiological studies suggest that changing diets are an important contributor. Dietary sodium intake warrants additional investigation because studies have shown high rates of sodium storage in the skin and that high sodium concentrations can trigger inflammatory responses involved in AD.

To study this, Katrina Abuabara will enroll 30 participants and employ a novel Magnetic Resonance Imaging (MRI) technique that has been shown to accurately quantify skin sodium concentration to examine whether a low-sodium diet can decrease skin sodium concentration and improve AD severity. The study presents a strong statistical analysis plan to identify key parameters for a future full-scale clinical trial.

If sodium restriction proves to be beneficial, it could lead to actionable impact on AD patients as a cost-effective, low-risk intervention that could be implemented in low resource settings.

The LEO Foundation Award 2021 – Region Americas

Grantee: Hunter Shain

Amount: USD 100,000

Grant category: LEO Foundation Awards

Year: 2021

Geography: USA

Hunter Shain is Assistant Professor at the University of California in San Francisco, USA.

He receives the award for his excellent and high-impact research in the field of dermatology and for his outstanding vision for research which outlines clear questions and approaches.

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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.

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

Grantee: Marta Giacomello, Assistant Professor, University of Padua

Amount: DKK 3,990,000

Grant category: Research grants in open competition

Year: 2021

Geography: Italy

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

Amount: DKK 3,923,850

Grant category: Research grants in open competition

Year: 2021

Geography: USA

The aim of this project is to study regeneration of new skin, complete with hair follicles, glands and adipose (fat) tissue.

Maksim Plikus will use a mouse model where many new hair follicles and adipocytes (fat cells) are formed from the center of large skin wounds. It is known that at the center of large wounds, there are cells (called myofibroblasts) that are essential for wound healing – and that these cells can ‘re-program’ into fat cells which are essential for scarless wound healing. This capacity to change is lost at the edges of large wounds and in smaller wounds.

The re-programming will be investigated by looking into how the myofibroblasts change during wound healing and identify the source of the fat cell growth factors responsible for the change. The findings will be used to better understand why these changes do not take place at wound edges but start from the wound center.

If successful, the project may pioneer a new research direction on regenerative wound healing and inspire new therapeutic approaches to scarring.

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

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

Amount: DKK 2,498,527

Grant category: Research grants in open competition

Year: 2021

Geography: United Kingdom

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.