Explore our grantees and awardees

Grant category: Serendipity Grants

Year: 2025

Geography: Denmark

Thomas Sicheritz-Pontén serendipitously found that ~15% of sequenced phages encode two adjacent, independently active endolysin genes, often with distinct catalytic and binding domains. In one example, each enzyme is active on its own, and modelling suggests they also form a complex. While developing a custom endolysin predictor incorporating gene neighbourhood context, he detected genomic patterns missed by other tools. Most studies focus on individual lysins or domains, overlooking adjacent full-length endolysin genes. His large-scale analysis of 21k phage genomes revealed this hidden trend and a possible unrecognised lysis strategy hiding in plain sight.

The project will begin with phage AA002, which infects Staphylococcus hominis, a contributor to human body odour. Thomas Sicheritz-Pontén will clone, express, and purify its two endolysins, assess their activity alone and in combination, and investigate synergy and complex formation. Structural modelling will provide mechanistic insight. In parallel, he will mine publicly available phage genomes to identify additional dual-endolysin systems and prioritise further candidates for testing on skin-associated bacteria under skin-like conditions.

This study will define a novel category of cooperative phage lytic enzymes, offering insights into phage genome organisation and enzyme evolution. Beyond fundamental discovery, these enzymes could serve as precise, microbiome-friendly actives for non-antibiotic applications such as next-generation deodorants.

Grant category: Serendipity Grants

Year: 2025

Geography: United Kingdom

Skin fibrosis is often a sequela of suboptimal wound healing following significant epidermal and/or dermal injury (burns, trauma, major surgeries). Fibrotic material replaces native skin with dense, non-functional connective tissue, ultimately resulting in loss of function and – in the most severe cases – leading to debilitating skin pathologies that limit movement and prevent patient reintegration into society. Ferreira’s lab hosts the only colony of spiny mouse in the UK (Acomys cahirinus). The spiny is, to date, the only mammal capable of completely regenerating skin wounds with minimal scarring following self-amputation. Sofia Ferreira Gonzalez is currently exploring the contribution of different dermal populations to this fibrosis-free wound healing.

Unexpectedly, Sofia Ferreira Gonzalez and colleagues found that spiny dermal fibroblasts have a highly plastic phenotype and are able to convert to many other cell types (neurons, myocytes, chondrocytes). Moreover, they found that spiny fibroblasts secrete factors that enhance migration and proliferation of human dermal fibroblasts and protect them from cellular senescence. Sofia Ferreira Gonzalez aims now to explore these results, defining which mechanisms drive plasticity, migration and proliferation in spiny fibroblasts and adapting them to human fibroblasts. By doing so, Sofia Ferreira Gonzalez aims to establish a radically new approach to skin trauma focused on stimulating tissue regeneration rather than suppressing fibrosis, which has the potential to revolutionize both care and patient outcomes.

Grant category: Serendipity Grants

Year: 2025

Geography: USA

Organisms are continuously bathed in a rich milieu of olfactory compounds. Defined by their ability to elicit the sense of smell, these molecules, and the receptors that sense them, have profound biological importance. Humans have hundreds of olfactory receptors, but paradoxically these are often expressed outside of the nasal cavity and on immune cells. Their function in these contexts is almost entirely unknown. The serendipitous finding illustrates that: a) olfactory receptors are enriched in inflamed skin and on lesion infiltrating lymphocytes; and b) odorants directly modulate lymphocyte function. Understanding the role and molecular mechanisms of these pathways in inflammation may open new avenues for treating skin disease with promise for targeted topical approaches.

To explore this serendipitous finding, the research project will combine in vivo models of skin inflammation with expertise in multiomic analyses of hidradenitis suppurativa (HS) and pyoderma gangrenosum (PG) patient tissues. The study will determine if exposure to olfactory molecules modulates skin inflammation in vivo, functionally dissect immune cell intrinsic olfactory signaling, and identify signatures of pathway activity in HS and PG.

This work will provide insight into the fundamental biology of immune-olfactory signaling and determine if there is functional relevance for skin inflammation. The project will also test the implications for HS and PG, where novel therapeutic approaches are urgently needed.

Grant category: Serendipity Grants

Year: 2025

Geography: Denmark

“Stretch-mediated tissue expansion” is used to grow extra skin during breast reconstruction. A mouse model mimicking this clinical process was used to unravel fibroblast-epithelial crosstalk supporting keratinocyte self-renewal. Unexpectedly, the research project found that stretching alters gene expression in Schwann cells, which support nerve function, and reduces touch sensitivity. However, how stretching impacts skin nerves and sensation remains unclear. In light of this serendipitous discovery, the project now plans to investigate how Schwann cells contribute to the regeneration and re-innervation of peripheral sensory neurons in stretched skin.

The new research project – SkinSense – will explore how stretching affects peripheral sensory neurons and Schwann cells, which are key to skin sensation. Single-cell transcriptomics and high-resolution imaging will be used to study how peripheral sensory neurons are affected in terms of structure, function, and repair. Based on these findings, gene therapy approaches using adeno-associated viruses will be tested to restore nerve function and recover skin sensation.

Loss of skin sensitivity after breast reconstruction can greatly affect the quality of life of women. Yet, the reasons behind this sensory loss are not well understood. SkinSense aims to uncover the biological causes of this dysfunction and test ways to restore sensation. This research could lead to new treatments that improve sensory outcomes for patients undergoing reconstructive surgery.

Grant category: Serendipity Grants

Year: 2025

Geography: Canada

Francesca Capon unexpectedly discovered that deleterious TCF3 mutations cause a severe form of atopic dermatitis (AD) associated with inflammatory bowel disease (IBD). By querying large-scale genetic repositories, the project also observed that common TCF3 alleles are associated with susceptibility to AD and IBD in the general population. TCF3 encodes a transcription factor that plays a key role in T cell differentiation. Thus, the project hypothesizes that TCF3 mutations cause abnormal T cell activation, leading to skin and gut inflammation. Given severe AD is a risk factor for IBD, it is further proposed that the study of TCF3 mutations will shed new light on mechanisms that may underpin both conditions.

The aim of the study is to validate the involvement of TCF3 in the pathogenesis of AD and IBD. This will be achieved by identifying the immune pathways that are altered by TCF3 dysfunction in skin and gut. The plan integrates:
i) in-vitro studies to determine the impact of TCF3 mutations on protein function
ii) immune phenotyping of T cells from individuals harbouring TCF3 mutations
iii) in-silico analyses to define transcriptional networks driven by TCF3

The project expects to identify TCF3-dependent pathways contributing to AD and IBD pathogenesis. This will shed new light on shared disease mechanisms with potential to inform targeted treatment of individuals affected by both conditions.

Grant category: Serendipity Grants

Year: 2025

Geography: USA

Hailey-Hailey disease (HHD) is a rare genetic disorder causing recurrent skin blistering and infections. Despite linkage to heterozygous (HET) mutations depleting the SPCA1 Golgi calcium pump 25 years ago, HHD lacks proven therapies. Cory Simpson’s LEO-funded research using in vitro HHD models led to two serendipitous discoveries that fuel this grant: (1) a JNK inhibitor intended as a negative control markedly strengthened adhesion among HET keratinocytes; (2) this led them to re-analyze RNAseq data, which revealed an overlooked aberration that may make HHD patients susceptible to pathogens like herpes simplex virus (HSV). Previously they focused on upregulated pathways amenable to drug inhibition; re-examining downregulated genes in HET cells, they found suppression of type 1 interferon (IFN) signaling. These data support their hypothesis that stress-induced JNK activation upon Golgi protein misfolding in HET keratinocytes weakens cell junctions to cause blistering and dampens IFN responses, facilitating viral infection.

To test these ideas, Cory Simpson required new tools and collaborators in immunology and virology, who provided biosensors to visualize and quantify JNK and type 1 IFN activity along with GFP-tagged HSV to infect the HHD models.

The planned work will test if modulating JNK or type 1 IFN in the HHD model can bolster epidermal integrity and suppress viral infection. Thus, the project has potential to directly impact treatment of patients with this orphan disease.

Grant category: Serendipity Grants

Year: 2024

Geography: USA

Ya-Chieh Hsu’s project investigates the mechanisms behind the unexpected observation that wound healing slows upon increased innervation of the surrounding tissue.

During testing of a virus-based tool designed to genetically manipulate skin cells Ya-Chieh Hsu and her team serendipitously discovered that increased innervation at a wound site slows healing and leads to increased scarring. This discovery suggests that wound-induced hyper-innervation may be important in driving scarring and fibrosis.

Grant category: Serendipity Grants

Year: 2024

Geography: United Kingdom

Shoba Amarnath’s project will investigate an unexpected link between regulatory T cells and the development of psoriatic arthritis (PsA).

In Shoba Amarnath’s original studies, based on her LEO Foundation Award in 2019, she sought to understand the role of immune cells in melanoma. As part of these investigations and to compare immune responses between cancer and autoimmunity, Shoba serendipitously found, through single-cell RNA and protein level analysis, that regulatory T cell (Treg) communication pathways with unconventional immune cells were significantly disrupted in psoriatic arthritis (PsA). This unbiased deep phenotyping specifically revealed a novel Treg specific regulatory mechanism in autoimmunity, especially crosstalk with osteoclast precursors (OCPs). It also has identified new targetable proteins in diseases where there is significant bone loss.

Grant category: Serendipity Grants

Year: 2024

Geography: USA

Philip Scumpia’s project will investigate a surprising discovery that links gender to differences in immune responses.

Philip Scumpia and his team created new formulations of biomaterials intended to improve cutaneous wound healing and decrease size of scars in his current LEO Foundation-funded project. While evaluating the immunological mechanisms, Philip and his team observed considerable variability in immune cell recruitment to the different hydrogels. After careful scrutiny they realized this variability was entirely due to the fact that female mice developed stronger immune responses to the hydrogel than male mice. Strikingly, female mice displayed a much earlier and more severe skin inflammation in other mouse models studied in the laboratory includingeczema, psoriasis, and sunburn.

Grant category: Serendipity Grants

Year: 2024

Geography: USA

Nathan Archer’s project investigates the surprising finding that dermal adipocytes and their crosstalk with eosinophils may play an important role in the development of atopic dermatitis.

The aim of Nathan Archer’s original project was to investigate the role of eosinophils, a type of immune cell, in the pronounced bacterial dysbiosis seen in relation to atopic dermatitis (AD). During those studies, Nathan Archer and his team serendipitously discovered an unexpected interaction of adipocytes with eosinophils in the skin, which was also associated with skin inflammation. This novel link will be investigated in Nathan’s project.