The Burghes lab is focused on understanding how reduced SMN levels give rise to Spinal Muscular Atrophy.  Increasing SMN protein using gene therapy, small molecule drugs and antisense oligonucleotides ameliorates SMA in cell culture, mouse models and in humans.  Yet the particular function of SMN that is disrupted remains unknown. To study biological pathway altered by loss of SMN, the lab has used transgenic mice and cell culture to study proteins that are known to physically interact with SMN.  This will give genetic evidence for the critical pathway and genes disrupted by SMN deficiency.  Furthermore, the lab is using long range Nanopore sequencing techniques to study genetic variation in discordant SMA sibling pairs with identical SMN2 copy numbers. Bioinformatic pipelines and novel methods of variant analysis are used to identify of genetic modifiers of SMA severity in humans.  Understanding the basic mechanism of SMA and SMN loss can lead to the identification of new therapeutic targets, which can then be tested in the Delta7 SMA mouse model and eventually translated to the clinic. In addition, the lab is developing next generation gene therapy for SMA through modification of the SMN2 gene using CRISPR technology. The Burghes Lab has expertise in the cloning of the SMN gene, transgenic mouse model creation, and the testing of therapeutics, including the development of gene therapy for SMA.