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.

Curing Cutaneous Calcinosis (CUCUC)

Grantee: Beate Lichtenberger, Principal Investigator, Medical University of Vienna

Amount: DKK 2,757,196

Grant category: Serendipity Grants

Year: 2023

Geography: Austria

Beate Lichtenberger investigates the mechanisms behind cutaneous calcinosis caused by over-activation of Hedgehog signaling in the dermis to improve treatment options.

Cutaneous calcinosis (CUC) is a debilitating condition characterized by the abnormal deposition of calcium salts in the skin and subcutaneous tissues, leading to pain, impaired mobility, and disfigurement. Despite its significant impact on patient quality of life, effective therapeutic interventions for CUC remain lacking, and there is no model system to study the disease. Beate Lichtenberger and her team serendipitously discovered that over-activation of Hedgehog (Hh) signaling in dermal fibroblasts leads to calcium precipitates and inflammation in limb and tail skin of mice, recapitulating the human disease

Beate Lichtenberger will elucidate the underlying mechanisms driving calcium deposition, inflammation, and tissue damage in cutaneous calcinosis. Furthermore, she will perform single cell RNA sequencing (scRNA-Seq) of human CUC tissue to assess which cell types apart from fibroblasts contribute to the pathogenesis and how

By advancing the understanding of the pathogenesis of CUC and developing targeted therapeutic strategies like repurposing of existing Hh inhibitors, Beate Lichtenberger’s project has the potential to revolutionize the treatment landscape and significantly improve the lives of individuals afflicted by this condition.

Exploring the serendipitous connection between a mitochondria fission protein and melanosomes maturation

Grantee: Marta Giacomello, Associate Professor, University of Padua

Amount: DKK 3,885,368

Grant category: Serendipity Grants

Year: 2023

Geography: Italy

Marta Giacomello aims to elucidate the role of a newly discovered mitochondrial fission protein in organelle maturation by exploring its impact on melanosome development and lipid droplet formation.

Melanogenesis, the process of synthesis and storage of the pigment responsible for skin color, melanin, occurs at specialized cell organelles named melanosomes. The mechanisms underlying melanin synthesis are not fully understood, but recent data suggest that mitochondrial physiology influences melanogenesis. Marta Giacomello and her team discovered that a mitochondrial fission factor, serendipitously found at the melanosome-mitochondria interface, controls the size of early melanosomes and melanin levels independently of its role in mitochondrial morphology.

The team aims to demonstrate that the identified mitochondria fission factor is a common regulator of organelle maturation, which exerts its specific effect based on its subcellular localization and interaction partners. They will first investigate its role in melanosome maturation, and then to generalize its function by extending the analysis to lipid droplets.

By elucidating how the identified fission factor switches from its mitochondrial to its melanosomal function, Marta Giacomello may generate milestone findings in the field of melanogenesis, and proof-of-concept evidence for its general role as a master regulator of organelles’ fission and maturation. Potentially, the results of this project could lead to breakthroughs in the fundamental understanding of cell biology.

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.