The LEO Foundation Award 2021 – Region Americas

Grantee: Hunter Shain, Assistant Professor, University of California - San Francisco

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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Keratinocyte contributions to inflammatory skin disease – Desmoglein 1 loss as a model

Grantee: Kathleen Green, Professor, Northwestern University - Illinois

Amount: DKK 3,025,870

Grant category: Research grants in open competition

Year: 2020

Geography: USA

The aim of this project is to study how the loss of a cell-cell adhesion protein called Desmoglein 1 helps drive activation of the immune system in inflammatory skin diseases.

The skin’s outermost layer, the epidermis, is made up of closely connected skin cells and plays a critical role in establishing an efficient barrier between the human body and the environment. Failure of this barrier in infectious, inflammatory and genetic skin diseases leads to clinical appearances driven by the interplay between the epidermis and the immune system.

Essential to establishing this epidermal barrier is a member of the desmosomal cadherin family of intercellular adhesion molecules, Desmoglein 1, whose best-known function is to connect neighboring skin cells together.  Professor Green and her team at Northwestern University, along with the group of Dr. Eran Cohen-Barak, Ha’Emek Medical Center Afula, Israel, are studying Desmoglein 1 functions that transcend their roles as ‘cell glue’. Their data suggest that loss of this protein increases immune responses and that the pathways activated are similar to those observed in inflammatory skin diseases like psoriasis.

Dr. Green and her team will use Desmoglein 1 deficient mice and Desmoglein 1 deficient human cells and tissues to determine the extent to which lack of this protein contributes to inflammatory skin diseases and to define molecular pathways that connect Desmoglein 1 to the immune system.

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: 2020

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: 2020

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: 2020

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: 2020

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.   

The LEO Foundation Award 2020 – Region Asia-Pacific

Grantee: Dr Yumi Matsuoka-Nakamura

Amount: USD 100,000

Grant category: LEO Foundation Awards

Year: 2020

Geography: Japan

Dr Yumi Matsuoka-Nakamura is Associate Professor at Immunology Frontier Research Center, Osaka University, Japan.

She receives the award for her internationally renowned skin research and her exceptional track record in in skin immunology, allergy and microbiology – and a great vision for her future endeavors.

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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. 

Genetic and Epigenetic Mechanisms of Steroid-Related Skin Inflammation

Grantee: Bryan Sun, Assistant Professor, University of California - San Diego

Amount: DKK 2,995,615

Grant category: Research grants in open competition

Year: 2020

Geography: USA

Steroids are a powerful class of medications that are widely used to treat inflammatory diseases. In most cases, steroids block an overactive immune response. However, in skin diseases such as rosacea and perioral dermatitis, the chronic use of steroids can lead to worsened inflammation. While these worsened cases are common, it is not understood why steroids worsen disease and make them even more difficult to treat.  

Bryan Sun and his research group recently discovered that an important cytokine which is elevated in rosacea, known as CCL20, is paradoxically activated in the skin by steroids. CCL20 increases inflammation by recruiting lymphocytes and dendritic cells. They found that steroid molecules directly bind and activate the CCL20 gene, overcoming the usual suppressive effects of steroids on inflammation. Based on this finding, they hypothesize that in some skin conditions, steroids directly activate the expression of genes that cause inflammation.  

The goal of this project is to systematically identify genetic and epigenetic steroid targets in skin cells. If successful, the results would allow identification of new therapeutic targets for rosacea and perioral dermatitis, and lead to valuable insight into other steroid-resistant inflammatory diseases.  

The 2021 Gordon Research Conference on Epithelial Differentiation and Keratinization (GRC-EDK)

Grantee: Salvador Aznar Benitah, Professor, Institute for Research in Biomedicine in Barcelona

Amount: DKK 204,130

Grant category: Research grants in open competition

Year: 2020

Geography: Spain

The 2021 Gordon Research Conference (GRC) on Epithelial Differentiation and Keratinization is the premier international meeting in epithelial biology.

The GRCs are known to promote intense interactions among the participants – who are experts in the field of the conference, leading to new knowledge, career mentoring, collaborations, and advancing as well as strengthening the field of the conference. This Gordon Research Conference will advance cutting-edge research in skin biology, promote translation of key findings to clinical practice, and further the careers of early stage investigators to maintain the highest level of innovation of this field in the future.

The LEO Foundation has previously provided support for the two previous Gordon Research Conferences.