Deep phenotyping of T regulatory cells in psoriatic arthritis highlights targetable mechanisms of disease
Grantee: Shoba Amarnath, Reader in Immune Regulation, Newcastle University
Amount: DKK 2,094,632
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.
The LEO Foundation Award 2024 – Region EMEA
Grantee: Claire Higgins, Reader, Department of Bioengineering, Imperial College London, UK
Amount: USD 100,000
Grant category: LEO Foundation Awards
Year: 2024
Geography: United Kingdom
Dr. Claire Higgins, is a Reader in the Department of Bioengineering at Imperial College London in the UK,
She receives the award in support of her impressive academic achievements and her remarkable leadership within her research group and to future generations of skin scientists. Her research aims to achieve scarless wound healing in human skin by studying the human hair follicle and understanding how it can be used as a model for skin healing.
Impact of ageing on epidermal cell fate plasticity
Grantee: Maria Alcolea, Associate Professor, University of Cambridge
Amount: DKK 3,887,952
Grant category: Research Grants in open competition
Year: 2024
Geography: United Kingdom
Maria Alcolea’s project explores how the plasticity of skin cells is affected by aging. Maria Alcolea and her team will study the molecular pathways that modulate changes in cell behaviour throughout life. The ultimate aim is to identify new targets to improve tissue regeneration and delay the regenerative decline associated with human skin ageing.
The ability of epithelial cells to rewire their program of cell fate in response to tissue perturbations has emerged as a new paradigm in stem cell biology. This plasticity improves the efficiency of tissue repair by enabling differentiated/lineage committed cells to reacquire stem cell-like behavior in response to damage. However, despite obvious implications for skin regeneration, virtually nothing is known about how the plastic capacity of skin cells is affected by ageing, and whether this contributes to changes in the normal physiology of the epidermis at later stages in life.
Maria Alcolea’s project will investigate the impact of aging in skin cell fate plasticity by making use of a novel in vivo model that enables tracing the fate of epidermal cells from the earliest stages of commitment towards differentiation. Newly developed tools offers a unique opportunity to identify the mechanisms dictating epithelial cell fate plasticity and determine whether aged-associated changes in this process hold the key to understand why the regenerative capacity of our skin declines over time. She will combine the lab’s expertise in in vivo quantitative lineage tracing, single-cell RNA sequencing approaches, and mathematical network analysis. Observations made in in vivo mouse models will be compared to human skin using a novel 3D organ culture.
Maria Alcolea’s project may contribute significantly to the emerging field of epidermal cell plasticity and provide a benchmark for identifying potential targets to partially reduce/reverse skin ageing.