Neuroinflammation and its resolution tip the balance between survival and loss of neurons and affects clinical progression in neurodegenerative disorders. The LIDo student will use a bioinformatic approach to merge and harness genetics and LC-MS-MS based Lipid Mediator profiling into coherent biological signals linked to rate of disease progression in amyotrophic lateral sclerosis, a fatal and clinically heterogeneous neurodegenerative disorder. Molecular signatures of fast and slow progression will provide disease biomarker and will be mined for drug repurposing. The work will draw from a unique repository of longitudinal data and matched biological samples from ALS patients and animal models of the disease.
Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N, Giovannoni G, Fratta P, Sidle K, Fish M, Orrell R, Howard R, Talbot K, Greensmith L, Kuhle J, Turner MR, Malaspina A. Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. Neurology. 2015 8; 85: 921.
Lu C, Allen K, Oei F, 4, Leoni, Kuhle J, Tree T, Fratta F, Sharma N, Sidle K, Howard R, Orrell R, Fish M, Greensmith L, Pearce N, Gallo V, Malaspina A. Systemic inflammatory response and neuromuscular involvement in Amyotrophic Lateral Sclerosis. Neurology, in press.
Dalli J, Colas RA, Quintana C., Barragan-Bradford D, Hurwitz S, Levy BD, Choi AM, Serhan CN, PhD1$ and Baron RM. Human sepsis eicosanoid and pro-resolving lipid mediator temporal profiles: correlations with survival and clinical outcomes. Critical Care Medicine in press.
Dalli J, Chiang N, Serhan CN. Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections. Nat Med. 2015; 21: 1071-5.
Postmus I*, Trompet S*, Deshmukh HA*, Barnes MR*, et al. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. 2014, Nature Comm, 5: 5068.