NPF-Funded Research

Project Summary:

Psoriasis involves inflammation and accelerated skin growth. Although genetic studies have shown that psoriasis is heritable, we still have a poor understanding of how genetics influences skin cells in psoriasis. Employing a new approach, I will culture skin cells from multiple donors together in a “village-in-a-dish”. Applying inflammatory signals that mimic psoriasis and measuring skin cell growth, I will then study genetic processes in individual cells. The data will show which genes are involved in the variation in skin cell response 1) between individuals and 2) between cells within an individual, thereby helping us to pinpoint targetable disease genes for each person. This will accelerate personalised medicine approaches in psoriasis.

How will your project help improve the lives of the 125 million affected by psoriatic disease?

Studying the genetics of people with psoriasis helps us understand the biological mechanisms that drive disease development. By identifying the genes and pathways most strongly linked to psoriasis at an individual level, this research will establish an important foundation for the development of more precise and effective therapies in the future. Ultimately, these findings could help support a more personalised approach to treatment, where therapies are better matched to an individual's biological profile, improving outcomes for people living with psoriatic disease.

Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?

During my PhD training at the University of Manchester I focused on "basic science" – that is, the molecular and cellular mechanisms underlying psoriasis, spending most of my time working with cells in the lab. However, I was fortunate to be able to attend several psoriasis clinics and outreach events alongside my supervisor, which gave me an opportunity to talk to people affected by the disease. I gained an appreciation for the challenges that they face, which gave perspective to my own research. Above all, I was struck by the lack of guarantee that any particular therapy would work for a certain patient. I believe that the genome holds key answers about disease that can be used to develop more effective treatment strategies, tailored to the individual.

This award is a critical step forward for me, as it will allow me to start pursuing my own research ideas for the first time. The results generated in this project will serve as a proof of concept for a larger-scale research program, in which I intend to incorporate additional critical cell types and stimulatory conditions, made possible by the flexible and scalable nature of the methods. I see a compelling opportunity for using this technology to better understand differences between patient treatment responses and disease phenotypes and comorbidities, such as psoriatic arthritis. This will help us to better predict disease outcomes in the future.

Researcher Profile:

Dr. Ray-Jones is a computational and experimental molecular biologist with experience in population genetics, epigenomics and functional perturbation experiments in human cells. Through her research, she explores the role of the non-coding regulatory genome and its impact on health and disease. Her studies have strongly focused on transcriptional enhancers; small but vital regulatory elements in the genome that often harbour genetic variants associated with complex disease. In her role within the Population Genomics department at the Erasmus MC, she is developing a program of research into identifying and annotating disease-causing genetic variants, genes and biological pathways, with an ultimate aim of improving the prediction and treatment of immune-mediated disease.