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.
Protein aggregation in host defense and skin inflammation
Grantee: Artur Schmidtchen, Professor, Dermatology and Venereology, Department of Clinical Sciences, Lund University
Amount: DKK 2,100,000
Grant category: Research Grants in open competition
Year: 2020
Geography: Sweden
The primary goal of this project is to identify and characterize the ‘aggregatome’, which describes the complete and complex network of proteins that are involved in the specific mechanism where the body – via its immune system – protects itself e.g. from bacteria. Subsequently, the project will explore and define the roles of the ‘aggregatome’ in inflammatory skin diseases.
The ultimate goal is to obtain new and deeper understanding of diseases affected by protein aggregation and potentially identify biomarkers of diagnostic significance.
In vivo gene editing for genodermatoses
Grantee: Thomas Kocher, Postdoc, EB House Austria, Salzburg
Amount: DKK 1,389,845
Grant category: Research Grants in open competition
Year: 2020
Geography: Austria
The goal of this project is to evaluate the translational and therapeutic potential of two in vivo CRISPR/Cas9 delivery methods. CRISPR/Cas9 is a gene-editing technology that enables researchers to edit parts of the genome by removing, adding or altering sections of a specific DNA sequence. Although CRISPR/Cas-based technologies hold great promise as genome editing tools in many genetic diseases, its clinical application, especially in genodermatoses, remains a big challenge.
To challenge this hurdle, CRISPR/Cas9 molecules will be delivered into the skin of a suitable animal model via two application methods: laser microporation and gene gun bombardment. The first method uses a laser to make micropores into the skin to allow the CRISPR/Cas9 constructs to enter the outer skin barrier and subsequently the target skin cells. The second method uses a “gene gun”, where gold particles covered with CRISPR/Cas9 constructs are shot directly into the skin/cells.
These constructs can then restore genetic defects in e.g. epidermolysis bullosa (EB) – a genetic condition that results in easy blistering of the skin and mucous membranes – which is used in this project as a model, and potentially cure the disease.
The project will investigate the potential of these two delivery methods in a mouse model using grafted human skin equivalents from expanded recessive dystrophic epidermolysis bullosa (RDEB) patient-derived fibroblasts and keratinocytes. If either delivery method proves efficient, it may hold the potential for development of future treatments, or even cure, of genetic skin diseases.
Identification and biological basis of immunomodulation of skin inflammation by S. epidermidis
Grantee: Peter Arkwright, Senior Lecturer, The University of Manchester
Amount: DKK 4,369,423
Grant category: Research Grants in open competition
Year: 2020
Geography: United Kingdom
The ultimate goal of this project is to contribute to the development of new medicines to treat bacterially induced eczema.
The project is a continuation of previous work supported by the LEO Foundation on the impact of bacterial infection, specifically caused by Staphylococcus Aureus (S. Aureus), on eczema. Here, a single factor secreted by S. Aureus was identified as the primary causative agent for eczema development or flare-up. Furthermore, it was also found that the naturally occurring variant, S. Epidermidis, has an inhibitory effect on eczema-induction.
The objective of the present project is to further elaborate on the disease-preventing effect of S. Epidermidis. First, the team will identify any factor(s) secreted by S. Epidermidis that inhibits eczema and then confirm its role by knocking out any relevant gene(s). Finally, the effect of any identified factor(s) on S. Aureus-induced eczema will be studied.
Deciphering the Role of Non-Coding RNAs in Epidermal Carcinogenesis
Grantee: Andor Pivarcsi, Senior lecturer/Associate Professor, Department of Medical Biochemistry and Microbiology (IMBIM), Uppsala Universitet, Uppsala
Amount: DKK 4,164,300
Grant category: Research Grants in open competition
Year: 2020
Geography: Sweden
The goal of this project is to investigate the potential role of long non-coding RNAs (lncRNAs, RNA molecules, which do not function through coding for protein, but by regulating other genes) in the development of the most common form of skin cancer with metastatic potential – Squamous Cell Carcinoma (SCC). Such RNAs are known to be key regulators of multiple cellular functions, tissue development and homeostasis, but their role in SCC is not clear. Andor Pivarcsi and his team have identified a group of long non-coding RNAs that have altered expression in this disease. As these lncRNAs may prove to be key players both in the development of cutaneous cancers and in the maintenance of normal skin homeostasis, they now want to investigate their function.
Andor Pivarcsi and his team will do so by defining the role and mechanism of action of selected lncRNAs by a combination of methods, including inhibiting them with anti-sense oligonucleotides, that will effectively prevent their association with natural binding partners. The results will improve our understanding of long non-coding RNAs in cutaneous malignancies and may pave the way towards improved antisense oligonucleotide-based skin cancer therapy.
Andor Pivarcsi is a former LEO Foundation Silver Award Winner (2010).
Rapid Clinical Assessment of Skin Barrier Function by Corneocytes Nanotexture
Grantee: Edwin En-Te Hwu, Associate Professor, Technical University of Denmark
Amount: DKK 2,824,593
Grant category: Research Grants in open competition
Year: 2020
Geography: Denmark
The goal of this project is to develop a clinically applicable imaging method for evaluation of atopic dermatitis (AD) development, progression and impact of therapeutic intervention.
It is known that AD is closely linked to the status of the skin barrier and therefore Edwin En-Te Hwu and his team will utilize a newly developed biomarker for skin barrier function, the Dermal Texture Index. This index is based on the number of circular nano-objects found on corneocytes (skin cells in the outermost part of the epidermis) of the skin by atomic force microscopy (AFM). However, the current analytical setup is both costly and has a limited throughput which makes it less suitable in a clinical setting.
The team has recently developed a new AFM technique and now aims to develop ‘Dermal AFM’, which will allow a ten times higher throughput in a clinically applicable unit. The unit may also help facilitate the understanding of the biology behind the observed corneocyte nanostructures.
The project is a collaboration between Denmark, Netherlands and Taiwan headed by DTU Health Technology.
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.
Global Psoriasis Atlas Phase II (GPA 2020-2023)
Grantee: Professor Chris Griffiths, University of Manchester
Amount: DKK 8,000,000
Grant category: Standalone grants
Year: 2020
Geography: United Kingdom
Psoriasis is a significant, life-long and currently incurable skin disease, which, according to the first edition of the Global Psoriasis Atlas (GPA), affects at least 60 million people worldwide.
The need to understand and uncover how psoriasis impacts both the individual and society at large is in demand. The Global Psoriasis Atlas is a long-term project that seeks to become the ‘go-to’ evidence-based resource within the understanding of psoriasis and its effects on people and society all over the World.
GPA Phase II (2020-2023)
The GPA Phase II is focused on continued research to establish robust data that address existing knowledge gaps within psoriasis on epidemiology, improving diagnosis, comorbid disease and economic impact.
Furthermore, if sufficient and robust data are available, the plan is to perform a pilot implementation study as part of GPA Phase II.
Addressing these key areas and how they differ between countries and regions will support the aim to provide better access to care for people with psoriasis worldwide.
Background
With a mission to ‘ensure that people with psoriasis, wherever they live in the world, have access to the best available care. The grant for the first version of the GPA was granted to Professor Griffiths and the University of Manchester in 2016.
The LEO Foundation has been main funder of the development of the first edition of the GPA through a 3-year grant of DKK 6,370,000 from 2017 – 2020. The GPA project has in its first three years focused on research into the global prevalence and incidence of psoriasis – resulting in the first edition of the GPA website which can be accessed free of charge here: Global Psoriasis Atlas online
The LEO Foundation Award 2020 – Region EMEA
Grantee: Dr. Ning Xu Landén
Amount: USD 100,000
Grant category: LEO Foundation Awards
Year: 2020
Geography: Sweden
Ning Xu Landén is an Associate Professor in experimental dermatology and venereology at the Department of Medicine, Solna at the Karolinska Institute in Sweden where she leads a successful research group. She is the author of around 50 scientific articles with more than 3000 citations.
Ning Xu Landén receives the award in recognition of her high impact research in wound healing.
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.