The purpose of this research program is to investigate the mechanisms of hereditary neurological diseases, with the ultimate intent of developing effective treatments for these disorders. The research focuses on three specific motor neuron diseases: autosomal recessive spinal muscular atrophy (SMA) due to deficiency of the protein SMN, X-linked spinal and bulbar muscular atrophy (SBMA) due to polyglutamine expansion in the androgen receptor, and distal spinal muscular atrophy/Charcot-Marie-Tooth disease type 2D (CMT2D) caused by mutations in tRNA synthetase. Specific research accomplishments in the past year include the following: (1) characterization of the role of IGF-1 and Akt in a cell culture model of SBMA, (2) evaluation of the efficacy of histone deacetylase and proteasome inhibitor treatment in a mouse model of SMA, (3) studies of the disease mechanisms of CMT2D and other hereditary forms of neuropathy and distal spinal muscular atrophy, (4) studies of the role of profilin in polyglutamine disease.
| Bennett, Craig L; Dastidar, Somasish G; Ling, Shuo-Chien et al. (2018) Senataxin mutations elicit motor neuron degeneration phenotypes and yield TDP-43 mislocalization in ALS4 mice and human patients. Acta Neuropathol 136:425-443 |
| Guber, Robert D; Schindler, Alice B; Budron, Maher S et al. (2018) Nucleocytoplasmic transport defect in a North American patient with ALS8. Ann Clin Transl Neurol 5:369-375 |
| Fernandopulle, Michael S; Prestil, Ryan; Grunseich, Christopher et al. (2018) Transcription Factor-Mediated Differentiation of Human iPSCs into Neurons. Curr Protoc Cell Biol 79:e51 |
| Grunseich, Christopher; Wang, Isabel X; Watts, Jason A et al. (2018) Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters. Mol Cell 69:426-437.e7 |
| Shi, Yingxiao; Lin, Shaoyu; Staats, Kim A et al. (2018) Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons. Nat Med 24:313-325 |
| Wang, Isabel X; Grunseich, Christopher; Fox, Jennifer et al. (2018) Human proteins that interact with RNA/DNA hybrids. Genome Res 28:1405-1414 |
| Manzano, Raquel; Sorarú, Gianni; Grunseich, Christopher et al. (2018) Beyond motor neurons: expanding the clinical spectrum in Kennedy's disease. J Neurol Neurosurg Psychiatry 89:808-812 |
| Pourshafie, Naemeh; Lee, Philip R; Chen, Ke-Lian et al. (2018) Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents. J Vis Exp : |
| Plehn, Jonathan F; Hasbani, Keren; Ernst, Inez et al. (2017) The Subclinical Cardiomyopathy of Friedreich's Ataxia in a Pediatric Population. J Card Fail : |
| Guber, Robert D; Takyar, Varun; Kokkinis, Angela et al. (2017) Nonalcoholic fatty liver disease in spinal and bulbar muscular atrophy. Neurology 89:2481-2490 |
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