Mechanisms of deconstruction and reconstruction of dermal fat in injury repair

Grantee: Esther Hoste, Assistant Professor, VIB-UGent Center for Inflammation Research

Amount: DKK 3,600,450

Grant category: Serendipity Grants

Year: 2024

Geography: Belgium

Esther Hoste’s project aims to elucidate the role of regulated cell death in adipocytes in relation to injury repair.

In preliminary studies, funded by her LEO Foundation Award in 2022, and investigating keratinocytes in injury repair, Esther Hoste and her team, to their surprise, observed cell death executioner events in adipocytes, implicating lytic and non-lytic adipocyte death in skin wound healing. While adipocyte plasticity is documented as an integral part of skin repair, little is known about the pathways mediating this process. However, rebuilding the adipocyte layer is crucial for restoring skin function after injury.

Boosting the phagocytic clearance of apoptotic cells for better wound healing during primary skin injury repair and upon secondary assaults

Grantee: Sophia Maschalidi, Assistant Professor, Universiteit Gent

Amount: DKK 3,986,871

Grant category: Research Grants in open competition

Year: 2024

Geography: Belgium

Sophia Maschalidi’s project explores the significance of enhancing efferocytosis – clearance of apoptotic cells by phagocytes – in skin injury repair, with the overall aim of accelerating wound closure.

The continual turnover of billions of cells in our bodies occurs as professional and non-professional phagocytes engulf cells dying via apoptosis. The efficiency of cell clearance or efferocytosis is remarkable and critical for homeostasis, minimizing inflammation and promoting repair. As the largest organ in our body, the skin acts as our first line of defense. Tissue repair after skin injury involves the clearance of apoptotic cells by phagocytes at the wound site as part of the process of resolving the inflammation and restoring the barrier. The importance of hastening barrier restoration is highlighted in chronic non-healing wounds, such as those associated with diabetes or in excess healing reactions after wounding leading to pathological scar tissue formation or fibrosis.

Sophia Maschalidi’s project aims to develop appropriate tools to enhance efferocytosis in vivo. Using novel techniques and sophisticated genetic mouse models, it will systematically address, for the first time, the importance of boosting efferocytosis during primary skin injury repair and in subsequent challenges. It will address how primary phagocytic experience shapes long-term changes on phagocytes and neighboring cells and whether this “efferocytic memory” shapes responses to secondary assaults.

Sophia Maschalidi’s project hopes to result in a fundamental understanding of the mechanisms and potential in boosting efferocytosis for therapeutic benefit in cutaneous wound management.