(MRC CASE) Mechanisms of Radiation-Induced Alopecia by Proton Beam and X-Ray Therapy and Prevention through Scalp Cooling

About the Project

Radiation-induced alopecia (RIA) is a distressing and potentially permanent hair loss disorder resulting from targeted radiotherapy used in the treatment of central nervous system tumours. RIA is a recognised effect of conventional radiotherapy (RT) using X-rays and has more recently been observed with patients undergoing proton beam therapy (PBT). However, the underlying mechanisms of RIA remain underexplored. As such, proven therapeutic options to prevent hair loss are not available, and current post-treatment interventions are often inadequate in restoring hair growth. As a result, RIA can have a significant psychological impact that may restrict the chance of someone fulfilling their full life potential. Through mechanisms that include reducing hair follicle division and metabolic activity, scalp cooling can effectively prevent both transient and permanent chemotherapy-induced alopecia (CIA). We hypothesise that scalp cooling can similarly reduce the vulnerability of hair follicle stem cells to the harmful effects of radiation, however this has yet to be investigated.

To address these gaps in knowledge, this PhD project will aim to systematically analyse the impact of RT and PBT on human scalp skin and scalp skin hair follicles and will test whether cooling can effectively protect scalp hairs from the damaging effects of radiation. To achieve this, the PhD student will study clinical tissue samples taken at different timepoints and employ ex vivo human hair follicle organ culture models of RIA (using x-ray and proton beam-based approaches) and cooling. The student will be fully trained in the development and utilisation of ex vivo human tissue models, as well as in the use of immunohistochemistry, in situ hybridization and transcriptomics analyses.

Proton beam irradiation will be carried out in the University of Manchester proton research facility at the Christie Proton Therapy Centre, the only PBT research facility of its kind in the UK, featuring unique infrastructure to allow proton irradiation under cooled conditions, putting us in a unique position to carry out this study. The PhD student will join the Manchester Hair Research Group which studies human hair follicle biology and inflammatory hair loss disorders as part of the NIHR Manchester BRC. The project will be supported by strong supervisory team and clinical and basic research collaborations, providing a breadth of experience, from the Centre from Dermatology Research, the Northern Care Alliance NHS Foundation Trust and Christie NHS Foundation Trust, PRECISE group, Division of Cancer Sciences. SME Paxman Coolers, support med-tech insight as world-leaders in scalp cooling.