Control of cutaneous immune responses by T follicular regulatory cells in systemic autoimmunity
Grantee: Søren Degn, Associate Professor, Aarhus University
Amount: DKK 2,795,064
Grant category: Research Grants in open competition
Year: 2022
Geography: Denmark
This project, led by Søren Degn, aims to investigate the role of a newly discovered immune cell, the T follicular regulatory cell (Tfr), in controlling systemic autoimmunity.
Søren Degn and his team have discovered that Tfrs are able to maintain tolerance in the skin even in the face of systemic inflammation, which in that case appear to be reversible, but also that if Tfr control in the skin fails, the systemic inflammation becomes irreversible and chronic.
Using a mouse model where Tfrs are selectively deleted, Søren and his team will investigate immune responses and identify which specific self-antigens are targeted when the tolerance maintained by the Tfrs is lost.
A single-cell dissection of the mechanisms underlying the ocular adverse effects of dupilumab in atopic dermatitis
Grantee: Francesca Capon, Associate Professor, King's College London
Amount: DKK 2,053,475
Grant category: Research Grants in open competition
Year: 2022
Geography: United Kingdom
This project, led by Francesca Capon, investigates the molecular and cellular mechanisms of dupilumab-associated conjunctivitis (inflammation of the eye), a comorbidity seen in one in three AD patients treated with the drug.
These mechanisms are poorly understood, and Francesca’s team wants to elucidate them by comparing immune profiles in blood samples from affected and non-affected patients. In addition, they will identify inflammatory molecules released by cultured immune cells treated with dupilumab to further understand the key signaling pathways.
The findings will enhance the understanding of dupilumab-induced conjunctivitis and eventually help improve treatment of patients with this condition.
The role of eosinophils in atopic dermatitis skin inflammation and itch
Grantee: Nathan Archer Ph.D., Assistant Professor, Johns Hopkins School of Medicine
Amount: DKK 3,783,727
Grant category: Research Grants in open competition
Year: 2022
Geography: USA
This project led by Dr. Nathan Archer investigates the interplay between bacterial colonization and a specific immune cell, the eosinophil, in development of atopic dermatitis (AD).
AD is a very common skin disease, particularly amongst young people, and the associated healthcare costs in the U.S. alone are estimated at USD 5.2 billion. Thus, there is a strong incentive to better understand the disease to improve its treatment.
The cause of AD is still unclear, but one interesting observation is that a specific type of immune cell, the eosinophil, infiltrates the affected areas and correlates with disease severity. The role of these eosinophils in AD remains unknown, but initial observations by Dr. Archer and his team point to a link between skin colonization of a specific bacteria, Staphylococcus aureus, and the observed infiltration – which may lead to both inflammation and itch. This bacteria-immune cell interaction is unusual, and Dr. Archer and his team will investigate the observed interaction in detail, with an aim to provide novel therapeutic targets for the treatment of AD.
Unveiling Novel Molecular Mechanisms Underpinning Chronic Pruritus and Developing Innovative Antipruritics
Grantee: Jianghui Meng, Assistant Professor, Dublin City University
Amount: DKK 2,200,000
Grant category: Research Grants in open competition
Year: 2022
Geography: Ireland
Chronic itch (pruritus) is a major symptom of numerous dermatological and systemic diseases, which substantially impairs patients’ quality of life, resulting in considerable socioeconomic costs. Current treatment options have insufficient efficacy or side effects, and do not treat the underlying cause of itch. Thus, there is a significant unmet medical need for a better efficacy, longer lasting and safer therapy.
Specifically, Jianghui and her team will focus on understanding the role of b-type natriuretic peptide (BNP) signaling, which is known to be pivotal in the development and transmission of itch, yet no effective therapeutics targeting this molecule have so far been developed. To address this knowledge gap, the team will investigate the pathways in detail, validate the involved molecules as potential targets for anti-itch drugs and develop therapeutic candidates that can interrupt several key molecular events of BNP signaling, including release of BNP and its pruritogenic effect.
Adherens Junction Dysfunction in Hidradenitis Suppurativa
Grantee: Amanda Nelson, Assistant Professor, The Pennsylvania State University
Amount: DKK 3,996,947
Grant category: Research Grants in open competition
Year: 2022
Geography: USA
Amanda Nelson’s project investigates the role of two proteins, E-cadherin and p120, in the relatively common inflammatory skin disease Hidradenitis Suppurativa (HS), which is characterized by skin lesions that cause intense pain, odor, drainage and scarring.
The cause of HS remains unclear, and this limits the current treatment options. The current hypothesis is that there is a blockage in the hair follicle unit, which triggers the immune response. Amanda and her team have found that E-cadherin and p120, both important for skin integrity, are lost in HS-affected skin, and their project seeks to understand how this loss may contribute to the hair follicle breakdown and subsequent inflammation. If the link is proven it may provide novel approaches for treatment of HS.
Towards a Cure of Genodermatoses: Intraepidermal Delivery of Gene Editing Tools Leveraging Smart Delivery Systems
Grantee: Sarah Hedtrich, Associate Professor, Charité Hospital Berlin
Amount: DKK 4,183,544
Grant category: Research Grants in open competition
Year: 2022
Geography: Germany
Sarah Hedtrich, who is also Associate Professor at the Faculty of Pharmaceutical Sciences of the University of British Columbia, leads this project focusing on developing novel ways to treat genetic skin diseases through intra-skin delivery methods.
Skin diseases caused by specific genetic defects (genodermatoses) are often rare but can be severe and even life threatening – like epidermolysis bullosa. To cure such diseases, the genetic errors which cause the diseases would need to be corrected. In recent years there have been major advances in targeted gene editing – not least with the CRISPR/Cas system which allows for both tissue- and cell-specific correction.
However, while the skin is readily accessible it has two features which impede such treatment: Firstly, the skin’s barrier function makes efficient delivery difficult, and secondly, as the skin is an epithelium with rapid turnover of the cells, a persistent cure involving gene editing must reach the stem cells which lie at the base of the epidermis, the outer layer of the skin.
Sarah and her team, with expertise in both dermatology, gene editing and topical drug delivery, aim to develop such a delivery system for gene correction treatments using microneedles and nanocapsules, and will investigate its efficiency in both human skin samples and bioengineered skin (disease) models.
Chemical compounds that impede the pathogenic effects of Staphylococcus aureus in atopic dermatitis
Grantee: Tim Tolker-Nielsen, Professor, University of Copenhagen
Amount: DKK 3,236,161
Grant category: Research Grants in open competition
Year: 2022
Geography: Denmark
The project by Tim Tolker-Nielsen aims to identify novel chemical compounds as potential drug leads for treating bacterial involvement in atopic dermatitis. The present project builds on findings from another LEO Foundation grant, which discovered a central factor, Sbi, responsible for the virulence (the ability to cause disease) of the bacteria Staphylococcus aureus in atopic dermatitis flares. As this factor appears to be unique to that bacterium it can be targeted with minimal impact expected on beneficial commensal (i.e. non-pathogenic) bacteria. Tim and his team will utilize existing libraries of chemical compounds to screen for lead candidates that can prevent the production of Sbi and which may be developed into a future treatment for atopic dermatitis flares.
The LEO Foundation Award 2022 – Region Americas
Grantee: Dr. Shadmehr Demehri, Associate Professor, Massachusetts General Hospital
Amount: USD 100,000
Grant category: LEO Foundation Awards
Year: 2022
Geography: USA
Dr. Shawn Demehri is Associate Professor at the Department of Dermatology at Massachusetts General Hospital, USA.
He receives the award for his more than noteworthy contributions to the dermatology field, his truly exciting trajectory within skin research as well as his clinical skills. Dr. Demehri is a brilliant and exceptionally talented physician-scientist who leads a creative and accomplished research team studying the intersection between the immune system and early cancer.
SID Resident and Post Doc Retreat
Grantee: Society for Investigative Dermatology
Amount: EUR 15,000
Grant category: Education and Awareness Grants
Year: 2022
Geography: USA
The SID mission is to advance the sciences relevant to skin disease through education, advocacy and scholarly exchange of scientific information.
The Copenhagen Translational Skin Immunology Biobank and Research Program (BIOSKIN)
Grantee: University of Copenhagen
Amount: DKK 40,000,000
Grant category: Standalone grants
Year: 2021
Geography: Denmark
Add-on Grant for the Leo Foundation Skin Immunology Research Center. Herlev and Gentofte Hospital together with LEO Foundation Skin Immunology Research Center at the University of Copenhagen establish a new research program and biobank with skin tissue and blood samples from 3,000 patients with illnesses such as psoriasis and eczema. The biobank is the first of its kind and will help shed light on some of the most common skin diseases. The goal is to collect data from 3,000 patients with skin diseases and in the long term also making data and knowledge available for researchers around the world.
The research program is established by the LEO Foundation Skin Immunology Research Center at the University of Copenhagen and the Department of Dermatology and Allergy at Herlev and Gentofte Hospital.
The program is supported with DKK 40 million from the LEO Foundation and co-financed with DKK 20 million from Herlev and Gentofte Hospital and LEO Foundation Skin Immunology Research Center.