Targeted and localized skin inflammation as a potential immunotherapy against cancer

Grantee: Vasileios Bekiaris, Associate Professor, Technical University of Denmark

Amount: DKK 3,987,557

Grant category: Serendipity Grants

Year: 2023

Geography: Denmark

Vasileios Bekiaris will investigate how an observed adverse impact of a drug candidate in psoriasis may be converted to a potential treatment of cancer.

Vasileios Bekiaris and his team have been studying the mechanisms by which psoriasis is induced for several years, and their goal was to find ways to suppress it. They have discovered a molecule that is necessary for the generation and function of the immune cells responsible for causing psoriasis. Moreover, they have access to a drug that targets and neutralizes this molecule, and therefore they thought that it could potentially inhibit psoriasis. Contrary to what they expected, the drug induced inflammation and exacerbated psoriasis instead of treating it. It is known that for many cancers, inflammation promotes favourable protective immunity and helps the efficacy of immunotherapy. Using a mouse melanoma model, Vasileios Bekiaris and his team have managed to generate data suggesting that the pro-inflammatory drug could in fact suppress tumour growth.

Vasileios Bekiaris will therefore investigate the drug’s potential in cancer treatment and, if successful, may open possibilities for a new immunotherapy against skin cancers. Vasileios Bekiaris and his team also believe that this data will continue their contribution towards understanding how skin inflammation is mediated.

An unexpected link between age-associated B cells and CD8 T cells

Grantee: Søren Degn, Associate Professor, Aarhus University

Amount: DKK 3,337,538

Grant category: Serendipity Grants

Year: 2023

Geography: Denmark

Søren Degn will investigate a novel link between age-related B cells (ABCs) and cytotoxic CD8+ T cells.

Søren Degn and his team have discovered a new and unexpected link between a type of immune cells that normally produce antibodies (B cells) and a type of immune cells that are responsible for eliminating the body’s own cells when they are infected or become cancerous (CD8+ T cells). Their preliminary findings indicate that this link may play an important role when the immune system is erroneously activated, when an infection cannot be cleared, or when a cancer is established. It is not known which exact signals are responsible for the communication between these two cell types, and whether it occurs directly or via a third-party messenger. However, it is known that it occurs in the spleen, an important immune organ, which filters the blood and prevents infections, but also plays a critical role in autoimmune diseases.

The intention of Søren Degn is to understand the cellular and molecular mechanisms behind this novel link. An increased understanding may enable new therapeutic strategies in the future across a range of important diseases such as inflammatory skin disorders, autoimmune diseases, and cancer.

Dr Abildgaard Fellowship 2023

Grantee: Dr. Terkild Brink Buus, Assistant Professor, University of Copenhagen, LEO Foundation Skin Immunology Research Center

Amount: DKK 12,000,000

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2023

Geography: Denmark

Project title: Staphylococcus aureus drives inflammation and disease activity in atopic dermatitis – novel approaches to old problems 

Fellowship theme: Skin Immunology and Inflammatory Skin Diseases

 

Terkild Brink Buus’ vision is to develop better strategies to manage Atopic Dermatitis (AD) and improve patient lives by increasing our understanding and providing vital insights into the underlying biology. AD is a debilitating disease affecting more than 30% of Danish children at great cost to patients, parents, and society.

Terkild Brink Buus’s project addresses the role of bacteria and their toxins in causing severe worsening of the AD. Building on his expertise in complex data analysis and research on aberrant T cells and skin inflammation, Terkild Brink Buus will explore how T cells – a vital part of our immune system – are hijacked by bacterial toxins to aggravate AD and how this can be counteracted by novel treatments.

Terkild Brink Buus hopes to increase our understanding of how bacteria and their toxins affect the skin and worsen the symptoms of AD patients. His research will provide the basis for initiating clinical trials of new treatment approaches targeting bacteria in AD patients as well as guidelines for how to determine which patients are most likely to benefit. Finally, he will provide several novel laboratory and analytical techniques that will be of high value to future research within inflammatory skin diseases.

Dr Abildgaard Fellowship 2023

Grantee: Dr. Stine Rønholt, Assistant Professor, University of Copenhagen, LEO Foundation Center for Cutaneous Drug Delivery

Amount: DKK 12,000,000

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2023

Geography: Denmark

Project title – ILnext: Unravelling the potential of ionic liquids as next generation cutaneous drug delivery systems

Fellowship theme: Skin Physiology and Cutaneous Drug Delivery

 

Stine Rønholt’s vision is to explore new ways to treat chronic skin issues (like eczema) directly on the skin. Today, such diseases are primarily treated by immunosuppressants, that upon systemic exposure can weaken the immune system. Atopic dermatitis is effectively treated by a type of medicine called JAK inhibitors, administered as tablets. Yet, direct administration of JAK inhibitors via the skin is hampered by the skin’s tough outer layer.

Stine Rønholt’s project will develop a new technology that treats eczema directly on the skin. To do so, Stine Rønholt is using a novel approach, “ionic liquids,” which can increase the drug solubility allowing for high dose treatment. Much like how sugar dissolves in water. This approach will help to deliver more medicine into the skin, targeting and treating eczema more effectively. Stine Rønholt’s goal is to figure out how to make this work for two specific JAK inhibitors, baricitinib and abrocitinib. Focus here is currently directed towards understanding how the ionic liquids used work together with the drugs, as well as what happens to the skin when the drug is applied. Even though the drug needs to be transported across the skin to where it is going to work, the technology should not cause any irritability to the skin. Special biophysical techniques are to be used to study all these things closely.

Stine Rønholt hopes to be able to deliver a high amount of medicine directly to a problem area without any uncomfortable procedures by using this approach. This could enhance treatment and lower the frequency of medicine required. Additionally, insights gained from Stine Rønholt’s project may pave the way for a new and improved method of addressing skin issues in a more efficient manner.

Dr Abildgaard Fellowship 2023

Grantee: Dr. Aida Hansen, Assistant Professor, University of Southern Denmark, Department of Molecular Medicine

Amount: DKK 12,000,000

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2023

Geography: Denmark

Project title – T-cell derived extracellular vesicles constitute pro-inflammatory packages that drive disease progression in psoriasis

Fellowship theme: Skin Immunology and Inflammatory Skin Diseases

 

Aida Hansen’s vision is to improve the treatment options for psoriasis patients by contributing to a more detailed understanding of the cellular cross-talk mediating the inflammatory processes in the disease. She aims to investigate a novel concept for cellular cross-talk, mediated by vesicular structures known as extracellular vesicles (EVs), that may drive inflammation in psoriasis.

Aida Hansen’s project builds upon knowledge that psoriasis is mainly driven by pro-inflammatory cytokines, and recently, it was discovered that cytokines are partly packaged into EVs. She hypothesizes that the majority of cytokines implicated in psoriasis are carried in specific subsets of EVs constituting “pro-inflammatory packages”. She will: 1) Do an in-depth investigation of the packaging of cytokines into EVs derived from patients with severe psoriasis, 2) Investigate the functional impact of specific EV-subpopulations in driving the inflammatory response in psoriasis, and 3) Explore the therapeutic concept for neutralizing specific disease-promoting EVs in psoriasis.

Aida Hansen hopes to contribute to a deeper understanding of how cytokines are being transported between cells and the potentially different biological properties of soluble cytokines compared to cytokines packaged into EVs. This is still poorly understood. The outcome of her project may lead to identification of new inflammatory pathways and novel depletion strategies for innovative therapeutic interventions to alleviate symptoms and improve the quality of life for patients with severe psoriasis.

Phage therapy to treat group A Streptococcus in Necrotizing Soft Tissue Infection

Grantee: Thomas Sicheritz-Pontén, Professor, University of Copenhagen

Amount: DKK 3,988,469

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

The project led by Thomas Sicheritz-Pontén from the Globe Institute at the University of Copenhagen, aims to carry out the fundamental work needed to develop targeted phage therapy (using bacteria-infecting viruses) to counter Necrotizing Soft Tissue Infections (NSTI).  This innovative treatment approach necessitates an in-depth understanding of the causative organisms, which will be achieved through sequencing these organisms and employing machine learning algorithms to predict their susceptibility to specific phages.

Necrotizing Soft Tissue Infections (NSTI), also known as “flesh-eating disease”, are rapidly escalating globally, posing a deadly bacterial threat that necessitates innovative therapeutic strategies due to its profound impact on human health. NSTI is characterized by aggressive skin manifestations primarily caused by Group A Streptococcus (Strep A). Although prompt surgery and antibiotics serve as the first-line treatment, infections often progress to necrosis, rendering antibiotics ineffective and often necessitating amputation and in worst case death.

Bacteriophages, or simply phages, offer a promising avenue to address this severe skin and soft tissue infection. Phages are viruses that selectively infect and eliminate bacteria, including antibiotic-resistant strains, without harming human cells.

Thomas Sicheritz-Pontén and team will do the fundamental work needed to identify prototype tailored phage therapies targeting Strep A. Along with his team, comprised of chief physicians from three different Danish hospitals, the UK Centre for Phage Research and the University of Copenhagen, Thomas Sicheritz-Pontén intends to identify phages capable of rapidly eradicating the bacteria, harness bacterial enzymes (endolysins), and employ phage satellites (mobile genetic elements that parasitize phages) for gene delivery.

By collaborating across research hubs, the team will decode Strep A’s genetic makeup, thereby facilitating the creation of precise phage cocktails and develop a novel molecular typing system to predict bacterial susceptibility, streamlining targeted phage treatments.

If successful, Thomas Sicheritz-Pontén’s project may greatly aid the battle against deadly NSTI infections through innovative development of phage therapy.

The ribotoxic stress response in inflammatory skin disease

Grantee: Simon Bekker-Jensen, Professor, University of Copenhagen, Center for Healthy Aging

Amount: DKK 3,823,440

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

Simon Bekker-Jensen’s project investigates the potential role of the NLRP1 (Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat and Pyrin Domain Containing 1) inflammasome in combination with the upstream activator Ribotoxic Stress Response (RSR) in AD and psoriasis.

Inflammatory and hyperproliferative skin diseases, including atopic dermatitis (AD) and psoriasis, are associated with cascades of inflammatory events. A key player in innate skin immunity is the NLRP1 inflammasome, which mediates inflammation and cell death in response to a wide array of stress insults. In human keratinocytes, NLRP1 was recently shown by Simon Bekker-Jensen’s team and others to be activated by the Ribotoxic Stress Response (RSR) upon exposure to UV-B irradiation and a range of bacterial toxins.

Based on their preliminary data demonstrating that the RSR also mediates inflammation and keratinocyte hyperproliferation in vivo, the team hypothesize that these pathways have broader implications for the pathogenesis of inflammatory skin diseases.

In Simon Bekker-Jensen’s project, the validity of the RSR as a therapeutic target in the common inflammatory skin diseases psoriasis and AD will be explored. By genetic deletion and pharmacological inhibition of the RSR, the team will interrogate this pathway in several mouse models of inflammatory skin diseases. In addition, they will generate a humanized NLRP1 mouse model to study the RSR-NLRP1 signaling axis in vivo. Finally, by using 3D organotypic skin models and skin biopsies from patients, they aim to firmly establish the role of the RSR in psoriasis and AD.

The long-term goal is to leverage this insight to develop new therapeutic options for the management and treatment of inflammatory skin diseases.

On track (På sporet – elever i 2. klasse lærer tal og algebra med læringsspor)

Grantee: Charlotte Skott, Professionshøjskolen Absalon

Amount: DKK 2,500,872

Grant category: Education and Awareness Grants

Year: 2023

Geography: Denmark

This project aims to apply a new research-based approach to enhance the teaching of mathematics in Denmark (called learning trajectories or Læringsspor in Danish), involving second-grade students and their mathematics teachers in all the public schools of Kalundborg as a first case. Learning trajectory constitutes an approach to numbers and algebra which has achieved promising results in international research. During the project, the Kalundborg mathematics teachers will learn about the approach and learning trajectories and be involved in developing educational material suited for a Danish context.

Science in reality (Videnskab i virkeligheden)

Grantee: Marie Erbs Ørbæk, CPH:DOX

Amount: DKK 980,000

Grant category: Education and Awareness Grants

Year: 2023

Geography: Denmark

CPH:DOX’s UNG:DOX program currently covers the greater Copenhagen area with a natural science educational focus during the two-week annual documentary film festival in March. Plans are underway to expand UNG:DOX to cover youth educations all over Denmark, providing year-round access. UNG:DOX offers upper secondary level students science documentaries from its international program, through streaming or live events, accompanied by expert lectures, scientist interviews, and additional resources for teachers.

Visit UNG:DOX’s webpage

Natural Science Marathon (Naturfagsmarathon)

Grantee: Maiken Lykke, Naturvidenskabernes Hus

Amount: DKK 2,000,000

Grant category: Education and Awareness Grants

Year: 2023

Geography: Denmark

This project continues the established ‘Naturfagsmaraton’ which provides a practice-oriented, engineering-inspired approach to STEM education with competitions revolving around real-world challenges, developed in collaboration with Danish companies. The project expands the current program aimed at 5th-6th grade pupils with an annual mini-marathon tailored for younger pupils.

Visit Natural Science Marathon’s webpage