Identifying biomarkers of aggressive multiple sclerosis

Our understanding of the immune pathogenesis of multiple sclerosis (MS) is incomplete. There is lack of clarity regarding why some patients have aggressive disease and there are no reliable biomarkers to delineate this at patient’s individual level. Autologous haematopoietic stem cell transplantation (HSCT) is being increasingly used as an intensive one-off treatment for such patients after having been demonstrated to be highly effective at inducing long-term remission. The treatment is not however without risk, meaning patient selection is paramount. Despite its success, some patients respond less well to HSCT and the reasons for this are unknown. Initially, the immune system is depleted with a conditioning (chemotherapy) regimen before it then regenerates with a higher level of immune tolerance that lasts well beyond the recovery of absolute lymphocyte numbers. The mechanism of action of HSCT has not been thoroughly defined, and there is limited knowledge of the reconstitution of the immune system, and its dynamics, in the blood and cerebrospinal fluid (CSF) of patients with MS.

This is a truly unique opportunity for the successful candidate to work alongside established academics with the aim to delineate the immune profile of peripheral blood and cerebrospinal fluid specimens obtained from patients with active relapsing remitting multiple sclerosis (MS) before and after autologous haematopoietic stem cell transplantation (HSCT) or high efficacy disease modifying treatment (DMT). These studies will provide crucial insight into disease mechanisms and control and they will inform biomarker development thereby enabling earlier diagnosis and better prognostication.

The postgraduate researcher will have access to state-of-the-art omics platforms (spectral flow cytometry, single-cell RNA sequencing) and will collect transcriptomic, proteomic, and functional data from primary patient samples (blood,  cerebrospinal fluid and haemopoietic stem cells). They will leverage advanced computational biology pipelines to integrate this information with clinical data, and to generate knowledge that is expected to advance the field.

The postgraduate researcher will be based in Nottingham Trent University’s John van Geest Cancer Research Centre and is expected to work very closely with and to receive training from the supervisory team within Sheffield Institute for Translational Neuroscience.

Interview details

Interviews will take place on the following dates: 13 March 2025