Janine KirbyMy research interests encompass the genetics of neurodegenerative diseases and how gene expression profiling can be used to investigate the pathogenic mechanisms of neurodegeneration and to identify diagnostic and prognostic biomarkers. I have used bth Sanger and next generation sequencing (exome and targeted) to screen known and establish novel causative genes in ALS and other neurodegenerative diseases (NDD). Most recently, I demonstrated the value of genetic screening in all patients with ALS, identifying actionable clinical results in patients who would normally not be offered it. I have performed genotype/phenotype correlations to link genetic, clinical, and neuropathological findings with multiple ALS genes including SOD1, TARDBP, FUS, C9ORF72, ANG, OPTN and most recently TBK1.

Sampling of CNS and peripheral tissues, as well as animal and cellular models, has been used to establish pathogenic mechanisms involved in both genetic and sporadic ALS. One of these studies established the dysregulation of NRF2, an important cell survival transcription factor, and this is now a therapeutic target for ALS. Expression profiling of CNS, blood, and fibroblast samples from genetic variants of MND and sporadic cases has also identified distinct gene signatures associated with the different genetic subtypes. Variation in miRNAs and other non-coding RNAs are also emerging as potential disease biomarkers. MiRNA profiling in serum and CSF by quantitative PCR, microarrays and small RNA sequencing has determined multiple miRNAs dysregulated in ALS. Finally, gene expression profiling of longitudinal blood samples from patient's blood samples have established the effect of low-dose interleukin-2 and demonstrated the effect of the drug on the blood transcriptome as well as the patient's personalized response, demonstrating the importance of a personalized medicine approach for the future. Read More Read Less