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.
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.
SID Resident and Post Doc Retreat
Grantee: Society for Investigative Dermatology
Amount: EUR 15,000
Grant category: Education and Awareness Grants
Year: 2020
Geography: USA
The SID mission is to advance the sciences relevant to skin disease through education, advocacy and scholarly exchange of scientific information.
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
This project aims to characterize a newly identified type of persistent rashes which resemble both eczema and psoriasis, but which differ at the molecular level.
Initial single-cell genetic screening of relevant immune cells from the rashes has identified a strong overlap in their genetic profile – especially in the expression of two specific cytokines, CCL5 and IL32 – cytokines are substances that are secreted by certain cells of the immune system and have an effect on other cells. At the same time, the classical markers of both atopic dermatitis and psoriasis are absent, suggesting that these rashes indeed may represent a novel condition.
The project aims to further identify and substantiate the genetic profiling by studying a larger patient population and link this to dupilumab treatment outcomes in order to stratify and optimize the treatment options available for this patient population.
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.