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.
SID Mentoring and Networking Circles Program
Grantee: Society for Investigative Dermatology
Amount: EUR 15,000
Grant category: Education and Awareness Grants
Year: 2021
Geography: USA
The SID mission is to advance the sciences relevant to skin disease through education, advocacy and scholarly exchange of scientific information.
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.
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.