Dr Gabriele De Luca is an Associate Professor and clinician-scientist at the Nuffield Department of Clinical Neurosciences, the University of Oxford. He completed his neurology training at the Mayo Clinic, Rochester, USA, where he was Chief Resident and Assistant Professor of Neurology. During his time at the Mayo Clinic he won several clinical awards including the Robert J. Filberg Fellowship, an award presented to the top Canadian trainee, and the Henry W. Woltman Award, a prize awarded to the top resident/fellow for clinical excellence in Neurology.
On completion of his neurology training he moved to Oxford, supported by the prestigious AANF/CMSC John F. Kurtzke Clinician-Scientist Development Award. He has developed a research programme examining the relationship between inflammation and neurodegeneration in multiple sclerosis and other degenerative diseases, such as Alzheimer’s disease. His research work has resulted in numerous publications, awards and invited platforms both nationally and internationally.
Molecular markers of multiple sclerosis disease progression
Clinical heterogeneity in multiple sclerosis (MS) is the norm. Evidence suggests that the immune gene variant HLA-DRB1*15 influences clinical outcome. Spinal cord (SC) pathology is common and contributes significantly to disability in the disease. Recent evidence suggests that HLA-DRB1*15 influences the extent of demyelination, inflammation and axonal loss in the SC. MS SC pathology is heterogeneous, being most marked in the upper part of the cord, especially in patients positive for HLA-DRB1*15. The heterogeneity of SC pathology along its length and between patients positive and negative for HLA-DRB1*15 implies that specific molecular pathways operate at different cord levels and are influenced by the genotype.
We aim to examine the deep proteome and functionally associated metabolome of post-mortem cerebrospinal fluid (CSF) and human SC tissue derived from patients with MS for whom genetic (HLA-DRB1*15 status) and detailed quantitative spinal cord pathology outcome measures will be obtained. Expression of key protein and small molecule candidates will be compared to pathological and clinical outcomes, e.g. time to wheelchair use.
The current focus on genetic, pathologic, proteomic and metabolomic correlations in the MS SC is novel. By evaluating the influence of genetic, proteomic and small molecule variations in tissues readily accessible during life (i.e. blood and CSF) on pathological changes (i.e. axonal loss), at present only detectable after death, the proposed study provides a unique translational platform to identify key biomarkers of clinical outcome and therapeutic targets that could be modulated to halt disease progression.Back to Winners page