Explore our grantees and awardees

Grant category: Research Grants

Year: 2022

Geography: Denmark

Claus Johansen’s project investigates the role of the protein ERAP2 in the pathogenesis of psoriasis.

Psoriasis is considered an autoimmune disease – i.e., a disease in which the T-cells of the immune system attack and destroy the body’s own cells by error. During an exposure to external factors (peptides, bacteria etc) a system of specialized cells engulfs, digests, and presents peptide fragments (antigens) of these external factors on their surface to the body’s immune cells – usually cytotoxic CD8+ T-cells – which, once activated, then surveil, identify, and destroy foreign elements containing that specific peptide or peptides with very similar overall structure. The peptides are presented by a specific receptor, called the human leukocyte antigen (HLA) receptor and it is well-known that a particular subtype of this receptor, the HLA-C receptor is dominant in psoriatic patients – still, concrete disease-specific self-antigens have not yet been identified. Recent results have indicated that a protein, ERAP2, which facilitates the association of antigen peptides to HLA receptors may have a role to play in the erroneous recognition of self-antigens in autoimmune diseases like psoriasis. Claus and his team aim to clarify the role of this protein in the current proposal.

If successful, their project may help shed further light on the autoimmune characteristics of psoriasis – and eventually help guide new treatment approaches.

Grant category: Research Grants

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.

Grant category: Research Grants

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.

Grant category: Research Grants

Year: 2021

Geography: Denmark

The research project by Professor Christian Olsen pursues a cutting-edge strategy for the treatment of skin infections.

Staphylococcal bacteria are the most common cause of skin and soft tissue infections, and with the rise of methicillin-resistant Staphylococcus aureus (MRSA), this new strategy could – if successful – help prevent minor infections from becoming severe medical conditions. Furthermore, the strategy could minimize the risk of emerging antibiotic resistance.

Bacteria produce and release molecules known as ‘virulence factors’ which cause damage. The production of these harmful molecules is regulated through a form of cell-to-cell communication called ‘quorum sensing’, where the concentration of virulence factors increases as a function of cell density. The present project aims to weaken the severity of bacterial skin infections by inhibiting ‘quorum sensing’ with synthetic auto-inducing peptide (AIP) analogs, and as a result, decrease the excretion of virulence factors.

‘Quorum sensing’ inhibition will target the severity of the bacterial infection, rather than the viability of the individual bacterium and represents an alternative to antibiotics, as there is no evolutionary pressure on the individual bacterium to develop towards a state that is not affected by these compounds. Therefore, minimal risk of emerging antibiotic resistance is to be expected from this strategy.

Grant category: Research Grants

Year: 2021

Geography: Denmark

This project aims to investigate the potential of using bacteria exchange or “microbiome transplant” as a viable treatment option for acne vulgaris.    

Acne vulgaris remains one of the most prevalent skin conditions worldwide affecting close to 10% of the population and impacting the quality of life of millions of people. Multiple factors contribute to acne, including genetics, excess sebum production, colonization of the skin by Cutibacterium acnes and an inflammatory cascade. Current treatments for acne such as retinoids and antibiotics have varied outcomes and side effects. As antibiotic resistance becomes an increasing concern in clinical practice, there is an unmet need for alternative treatment approaches.   

The team have previously identified a range of bacterial strains, isolated from healthy skin, that can selectively inhibit acne-associated Cutibacterium acnes strains. The current project takes a microbiome transplantation approach to acne treatment, utilizing a pre-existing in-house library of more than 1000 bacterial strains and testing their ability to modulate the skin microbiome and reduce acne symptoms in patients with mild-to-moderate acne.  

This project may pave the way for developing a personalized treatment to a very common skin disease while avoiding the issue of antibiotic resistance. 

Grant category: Research Grants

Year: 2021

Geography: Denmark

The project aims to better understand the molecular basis of Hidradenitis Suppurativa (HS). HS is a debilitating chronic skin disease characterized by the formation of painful nodules and abscesses predominantly in the armpits, groins, and buttocks. With time, the disease may progress resulting in persisting tunnels in the skin and pronounced scarring. While there are many treatment options for HS, successful management often remains difficult and sometimes elusive – which likely reflects the still incompletely understood pathogenesis.  

Simon Francis Thomsen and his team will approach this by doing a large-scale, prospective study where they determine the protein composition of blood from more than 500 HS patients. They will follow the changes during disease progression (identified as Hurley stage I to III) to identify key biomarkers and signaling pathways specific for the disease.  

The study is a unique translational endeavor which brings together clinical dermatologists with basic scientists to explore and characterize the serum proteome of patients with HS through analysis of blood serum samples obtained at the Department of Dermatology, Bispebjerg Hospital.  

Grant category: Research Grants

Year: 2020

Geography: Denmark

Patients with atopic dermatitis (AD) are often colonized by the bacterial pathogen, Staphylococcus aureus (S. Aureus). S. aureus produces a large variety of toxins that contribute to the severity of AD and expression of these toxins is controlled by a cell-cell communication process called “quorum sensing”.  

Professor Ingmer and her team has previously demonstrated that some bacteria produce signaling molecules, which in S. aureus abolish toxin production through repression of quorum sensing and preliminary analyses indicate that probiotic bacteria also belong to this group. 

Thus, the goal of this project is to deliver results addressing the efficacy of probiotics. The project proposes that probiotic bacteria can reduce S. aureus toxin production and that some of the reported benefits of probiotics in AD may be associated with such activity. 

Professor Ingmer will address this hypothesis in collaboration with Statens Serum Institut, the LEO Foundation Skin Immunology Research Center, UCPH and Department of Drug Design and Pharmacology, UCPH. 

Grant category: Research Grants

Year: 2020

Geography: Denmark

Psoriasis is an inflammatory disease characterized by overproduction of tissue-damaging cytokines by immune cells and keratinocytes. Central cytokines in psoriasis are TNF (tumor necrosis factor) and IL-17 (interleukin 17), which are currently approved therapeutic drug targets. To improve current therapies targeted towards TNF and IL-17, it is important to better understand the biology of the two cytokines in relation to psoriasis.  

The goal of this project is to confirm that two enzymes known as cIAPs (cellular inhibitors of apoptosis proteins) play a central role in psoriasis.  

The two cIAPs are believed to modulate the response of the immune system and of keratinocytes to TNF in order to fine-tune IL-17 production. The project will investigate whether lack of the two cIAPs or their pharmacologic inhibition makes the immune response less pathogenic and reduces the pro-inflammatory nature of keratinocytes during psoriasis.  

Grant category: Research Grants

Year: 2020

Geography: Denmark

Atopic Dermatitis (AD) is a common inflammatory skin disease affecting 15% of children and 3-5% of adults. AD is associated with the risk for developing co-morbidities such as other atopic diseases (food allergy, asthma, and rhinitis) and infections. Co-morbidities are believed to occur because of functional changes in the immune system of AD patients, however, it remains unknown how these changes are established. Emerging experimental studies suggest the existence of a skin-gut immune axis, but the role for the gut remains largely unexplored in AD.

The goal of this project is to determine if AD changes the bacterial microbiota composition and function in the gut, alters the intestinal and systemic immune system, and increases the risk for food allergy co-morbidity via oral sensitization. The project hypothesizes that AD drives dysregulated immune responses to the gut microbiota, which in turn changes the immune system giving rise to atopic co-morbidities and risk for infections. In other words, it is envisaged that AD patients become “allergic” to the bacteria present in their intestine – leading to a “persistent allergic reaction” due to continuous presence of bacteria in the intestine.

The project will use a rat model of AD to investigate the hypothesis and perform a human case-control study to support the clinical relevance of the findings. Identification of bacterial drivers of persistent type-2 inflammation could open new avenues for the prevention and treatment of AD and related co-morbidities.

Grant category: Research Grants

Year: 2020

Geography: Denmark

This project aims to answer key questions related to a recently discovered new class of biomolecules, called circular RNAs. These RNA molecules appear to have an important role in early immune responses and the project aims to functionally characterize them in psoriasis patients and compare the results with data from healthy controls.

To study the RNA molecules, the project uses a combination of traditional molecular biology approaches and high-throughput technologies such as RNA-sequencing and NanoString technology.

In summary, this project aims to shed light on the distribution and functional relevance of circular RNAs within psoriatic plagues as well as in normal skin and potentially open new avenues for better treatment and management of psoriasis.