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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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.

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.  

Investigation of genetic variation and development of genetically defined cell models for Acne vulgaris therapeutic and cosmetic products evaluation

Grantee: George Church, Professor at Harvard Medical School, Harvard University and MIT, Cambridge, MA

Amount: DKK 3,926,475

Grant category: Research grants in open competition

Year: 2020

Geography: USA

Summary available soon.

Molecular investigation of CCL5-hi chronic adult rashes (CCARs)

Grantee: Raymond Cho, Associate Professor, Dermatology, School of Medicine, University of California San Francisco, CA

Amount: DKK 3,330,056

Grant category: Research grants in open competition

Year: 2020

Geography: USA

Summary available soon.

Targeting Aberrant STAT3 Signaling in CTCL

Grantee: Sergei Koralov, Associate Professor, NYU Langone, NY

Amount: DKK 2,676,248

Grant category: Research grants in open competition

Year: 2020

Geography: USA

The goal of this project is to elucidate the mechanism behind the beneficial effects of atovaquone, a well-tolerated anti-microbial drug, on the rare type of skin cancer – the T-cell lymphoma (CTCL). It is known that atovaquone inhibits malignant cells from growing and may induce cell death, but the precise mechanism(s) is not known.

Sergei Koralov and his team have previously developed an animal model of the CTCL disease and will use this along with cells from patients to investigate the effects of atovaquone. Specifically, they will look at how the drug affects the gene regulating protein STAT3 as hyperactivation of this has shown to be critically important in the development of cancerous T-cells.

Given the outstanding tolerability of atovaquone, it is believed that if its mode of action can be deciphered it may prove a powerful tool in the future for treatment of malignant and inflammatory diseases.

The LEO Foundation Award 2020 – Region Americas

Grantee: Dr. Ya-Chieh Hsu

Amount: USD 100,000

Grant category: LEO Foundation Awards

Year: 2020

Geography: USA

Ya-Chieh Hsu is the Alvin and Esta Star Associate Professor at the Department of Stem Cell and Regenerative Biology at Harvard University, Cambridge, USA.

Ya-Chieh Hsu receives the award in recognition of her research achievements in studying cell-cell interactions and how systemic changes in the body influence these interactions in the skin.

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The LEO Foundation Award 2019 – Region Americas

Grantee: Maksim Plikus

Amount: USD 100,000

Grant category: LEO Foundation Awards

Year: 2019

Geography: USA

Maksim Plikus is Associate Professor at the Department of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, USA

He receives 100,000 USD for his research in skin stem cells and regeneration.

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