Teach First Danmark

Grantee: Jesper Christensen

Amount: DKK 1,443,750

Grant category: Education and Awareness Grants

Year: 2023

Geography: Denmark

Teach First is a nonprofit recruitment program that enrolls academics in an employment-based training program to become certified schoolteachers, mainly within STEM fields and in schools in socio-economically disadvantaged areas. The purpose of the project is to double the reach of the program by preparing an expansion to western Denmark and to increase the financial sustainability of the program via economy of scale and increase of schools’ share of costs.

Gordon Research Conferences

Grantee: Gordon Research Conferences

Amount: DKK 156,723

Grant category: Research Networking

Year: 2023

Geography: USA

The Barrier Function of Mammalian Skin conference theme is “An Intelligent and Personalized Skin Barrier: Integration and Translation of Cell and Molecular Biology, Bioengineering and Physical Chemistry”. Keynote sessions include presentations on topics such as “Inflammation in Barrier Function and Dysfunction”, “Big Data to Knowledge: Models, Diagnostics and Therapies” and “The “Next Big Question on the Skin Barrier”. 

The Gordon Research Conferences are renowned for their excellent scientific programs and are unique in that each conferee agrees that any information presented at a Gordon Research Conference or Gordon Research Seminar, whether in a formal talk, poster session, or discussion, is a private communication from the individual making the contribution and is presented with the restriction that such information is not for public use. 

Montagna Symposia on the Biology of Skin

Grantee: Oregon Health and Science University, Department of Dermatology

Amount: DKK 181,468

Grant category: Research Networking

Year: 2023

Geography: USA

The Montagna Symposia on the Biology of Skin are a very well-established conference, similar to a Gorden Conference, bridging the gap between basic research and dermatology. The meeting brings together scientists and physicians from academics to industry to foster interdisciplinary communication and collaboration in basic, translational and clinical research and practice, facilitating development of new collaborations, research and therapies for cancer, inflammatory diseases and other skin conditions. It provides a venue for the participation of high-profile, established speakers and up-and-coming stars in skin disease research and dermatology practice from around the world. The meeting facilitates the coming together of established researchers and clinicians with residents, fellows, and students; and representatives from government, foundations, and industry in a variety of fields and specialties, fostering the cross-pollination of ideas that is at the heart of breakthroughs in translational dermatology. 

Outside-to-inside: understanding aberrant proteolysis in primary barrier defects as drivers of atopic dermatitis

Grantee: Ulrich auf dem Keller, Professor, Technical University of Denmark

Amount: DKK 2,865,186

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

This project of Ulrich auf dem Keller aims to elucidate the potential role of a set of recently discovered proteins in atopic dermatitis that may contribute to disease development.

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects people of all ages. It is one of the most common skin diseases, affecting approximately 10-20% of children and 1-3% of adults worldwide. AD can be a frustrating and uncomfortable condition that can significantly impact a person’s quality of life.

Despite extensive research it is not fully clear, if AD is primarily caused by a defect barrier function of the skin, allowing uncontrolled entry of environmental allergens that trigger an immune response, or by immunological disorders that in turn weaken the skin’s protective barrier, exaggerating the disease in a vicious cycle. Most likely, both contribute to predisposition and development of AD, but there are differences between patients which call for customized therapies.

Together with basic skin researchers in Switzerland and dermatologists in Germany, Ulrich auf dem Keller has identified proteins in non-lesional skin of AD patients whose activities might impair skin barrier integrity mostly independent of an immune response. This project will use human skin models and advanced protein analytics to understand if and how they might exert these detrimental activities and thereby contribute to predisposition to AD in affected individuals. Moreover, they will test their findings in samples from AD patients with a long-term aim to contribute to new strategies for development of therapeutics as alternatives to frequently applied emollients in barrier repair therapy.

A Backpack-based Macrophage Therapy for Dermal Wound Healing

Grantee: Samir Mitragotri, Professor, Harvard John A Paulson School of Engineering and Applied Sciences

Amount: DKK 3,954,190

Grant category: Research Grants in open competition

Year: 2023

Geography: USA

Macrophages, especially anti-inflammatory macrophages, are essential biological players in the process of dermal wound healing. However, maintaining an M2 phenotype within the inflamed wound microenvironment is quite challenging due to secretion of inflammatory cytokines from the wound. To overcome this limitation, Samir Mitragotri and his team have invented polymer micro-disks (“backpacks”) that carry potent anti-inflammatory agents. These “backpacks” are uniquely designed to possess a discoidal shape which keeps them attached to the monocyte/macrophage surface without them being taken up by the cell, and ensures continuous delivery of the anti-inflammatory agents to the cell carrying the backpack without elevating systemic drug concentrations. The project aims to develop a protocol to deliver such “backpack”-laden monocytes only once into the wound, where they can differentiate into macrophages and maintain themselves in the anti-inflammatory phenotype for an adequate time period to induce wound healing. The “backpack” technology has been pioneered by Samir Mitragotri and his lab. This novel strategy appears to have a unique advantage to control macrophage phenotype only for a pre-determined time, thus representing a promising new approach to dermal wound healing treatment.

Skin bacteria lipopeptides: key modulators of keratinocyte immune responses and atopic dermatitis

Grantee: Peter Arkwright, Senior Lecturer, The University of Manchester

Amount: DKK 4,163,557

Grant category: Research Grants in open competition

Year: 2023

Geography: United Kingdom

Dr Peter Arkwright’s project aims to functionally characterize a group of recently discovered anti-inflammatory bacterial substances and investigate their potential therapeutic value in atopic dermatitis.

Staphylococcus aureus is unique in being the only bacterial species that consistently triggers flares in atopic dermatitis (AD). In previous work, also supported by the LEO Foundation, Dr Peter Arkwright, Dr Jo Pennock, and their team at the University of Manchester discovered “Sbi” as the unique factor produced by this bacterium that initiates AD in skin cells. Recently, they have identified factors produced by skin bacteria that completely block Staphylococcus aureus-induced AD, both in the lab and in an eczema mouse model. These factors are small, stable chemicals, made up of both fats and small proteins (lipopeptides).

In a collaboration with Professor Hiroshi Matsuda and Professor Akane Tanaka in Tokyo, Japan, they will apply lipopeptides derived from different bacteria to the skin of mice with AD to determine which are most effective at reducing the clinical dermatitis, itch, and skin damage. They will also explore how these factors work, using cell, protein, and lipid staining techniques. By purifying and characterizing these chemically stable immunosuppressive lipopeptides it is hoped that promising candidates identified here can be taken forward into clinical trials to develop novel therapies for AD.

Curing calcinosis: Dystrophic calcinosis in patients with Systemic Sclerosis undergoing treatment with Sodium Thiosulfate – Assessed by novel biomarkers and diagnostic imaging

Grantee: Mette Mogensen, Chief Consultant, Associate Professor, Bispebjerg and Frederiksberg Hospital

Amount: DKK 3,322,500

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

This research project aims to synergistically improve patient treatment and improve understanding of the underlying biological and chemical mechanisms of cutaneous dystrophic calcinosis (DC) – a disease causing exaggerated deposition of calcium salts in skin.

These pathological calcifications cause severe ulcerations and pain in patients with systemic sclerosis (SSc) and negatively impact their quality of life. Today, reliable methods of quantifying the distribution, volume and composition of calcium crystal deposits are lacking.

Combining the expertise of data scientists and molecular biologists with medical experts in the field of radiology, dermatology, and rheumatology, Mette Mogensen and her team will create a new approach for quantifying calcium crystal deposits in skin and soft tissue in patients suffering from SSc, which is highly needed to monitor disease progression and potential treatment effects in future clinical trials. Several smaller studies have shown a potential for treating DC using sodium thiosulphate (STS). The aim of this study is to explore the characteristics of DC and investigate how STS treatment effects can be monitored over time with novel biomarkers (from blood and skin biopsies) and by advanced imaging technologies.

The vision is to cure calcinosis and the goal of this project is to increase quality of life for patients by development of an effective, targeted treatment that may offer therapeutic potential to all DC patients globally.

Citrullination in hair growth and alopecia

Grantee: Maria Genander, Assistant Professor, Karolinska Institutet

Amount: DKK 4,020,645

Grant category: Research Grants in open competition

Year: 2023

Geography: Sweden

Maria Genander’s project aims to understand the physiological role of the enzymes PADI3 and PADI4, which convert the amino acid arginine to citrulline, in normal hair growth – to ultimately better understand the changes that happen during unwanted hair loss, alopecia.

Hair follicle (HF) growth, leading to the generation of the hair shaft, requires coordinated development of the cells that make up hair. Protein modifications act to fine-tune the action of the signaling that leads to cellular maturation and differentiation and impacts directly on the properties of structural proteins required for hair formation. In this project, Maria Genander and her team investigate the expression of the protein-modifying enzymes PADI3 and PADI4 in the HF to understand the functional impact of PADI-mediated citrullination on cell differentiation and hair growth. Preliminary data indicate that PADI4 restricts proliferation of HF progenitor cells committed to the hair shaft lineage. Using sophisticated methodology, they aim to decipher mechanistically how PADI4 influences HF lineage progression. In addition, they will use in-utero lentiviral injections in mice to probe the function of PADI3a and PADI3b to understand how distinct PADI3 isoforms impacts hair formation and the development of alopecia.

Collectively, Maria Genander’s work will focus on addressing citrullination in hair follicle growth and hair formation. Understanding normal hair follicle development is a prerequisite for development of therapeutic strategies targeting alopecia.

Unravel fibroblast-epithelial crosstalk supporting keratinocytes self-renewal to improve skin graft production

Grantee: Mariaceleste Aragona, Associate Professor, Novo Nordisk Foundation Centre for Stem Cell Medicine

Amount: DKK 3,999,975

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

In this project Mariaceleste Aragona, in collaboration with Elena Enzo (University of Modena and Reggio Emilia, Italy), aims at the optimization of skin graft production for regenerative and replacement purpose.

Skin grafts for transplantation purposes are generated from epidermal stem cells. These regenerative therapies are life-saving procedures and have been demonstrated to be successful and safe for the treatment of burns and severe genetic diseases. Long lasting skin regeneration requires the correct amount of stem cells (SCs) in the graft. However, the treatment of large burns or skin replacement therapy in elderly patients are still challenging.

In such situations, the limited area of donor sites, and the physiological reduction of the number of SCs results in insufficient availability of SCs for graft production. A way to efficiently produce more SCs is to enforce their self-renewing – the process of generating more SCs – capacity.

A condition that forces SCs to increase their self-renewal capacity is tissue stretching. In this project, Mariaceleste Aragona aims to generate a comprehensive atlas of the changes occurring in space and time during tissue stretching. Based on this atlas, they will elucidate the signaling molecules instructing SC’s self-renewal and identify options to target such molecules. This knowledge will be used to develop cell culture conditions to ameliorate skin graft productions for clinical application.

Collectively, such insights will provide new fundamental knowledge on the biology of SCs and this approach may improve the clinical success of skin regenerative and replacement therapies to the benefit of patients.

Understanding the role of FOXO4-mediated regulatory network in the biology of Th22 cells

Grantee: Kilian Eyerich, Chief Physician, Karolinska Institutet

Amount: DKK 2,045,000

Grant category: Research Grants in open competition

Year: 2023

Geography: Sweden

Kilian Eyerich’s project aims to investigate the role of the transcription factor FOXO4 in the development of a specific type of T cells – the Th22 cells.

Th22 cells are a distinct subset of CD4+ T helper cells, and their effector cytokine IL-22 plays a protective role in barrier homeostasis by regulating innate immune responses, antimicrobial defense mechanisms, and wound healing. The natural differentiation of naive CD4+ T cells into the Th22 lineage and production of IL-22 by these cells is a multifactorial process that is not yet fully understood. In this project, Kilian Eyerich, along with colleague Kunal Das Mahapatra and team, will investigate the hypothesis that the transcription factor FOXO4 is a novel regulator of IL-22 production in Th22 cells. Pilot data show that FOXO4 is upregulated in human skin derived Th22 clones. It has a pattern of early induction and steady increment during Th22 differentiation, which is governed by the cytokines IL-6 and TNF-a. Moreover, the team has shown that silencing FOXO4 in naive T cells in a

Th22-inducing condition leads to reduced IL-22 secretion and that there is a protective effect of this regulation on epithelial cells, as observed in a scratch assay where keratinocytes, cultured in the supernatant from FOXO4-depleted T cells, migrated less efficiently.

The proposed project therefore aims to perform a deeper characterization of FOXO4 in Th22 cells by systematically identifying FOXO4-regulated genes, downstream pathways, and potential co-factors. In addition, the extrinsic role of FOXO4 on keratinocytes and skin wound healing will be assessed by ex vivo assays and analysis of multi-omics data from human patients.

Taken together, this project may offer novel insights into the regulatory processes in development and function of Th22 T cells.