In 2007, Simon was appointed as a Consultant Neurologist and Clinical Lead of the National Prion Clinic based at the National Hospital for Neurology and Neurosurgery, UCLH. Simon leads the Human Genetics, Bioinformatics and Epigenetics programme and is also co-lead of the Clinical programme. His research interest include treatment and designs for clinical trials in CJD and other human prion disease, the discovery of biomarkers, genetic and epigenetic factors that cause or modify prion disease. He was made a Professor at UCL in 2014, NIHR Senior Investigator in 2018 and Deputy Director of the MRC Prion at UCL in 2018.