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. Recently, the research has focused on three specific neuromuscular 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 myofibrillar myopathy caused by mutations in ZASP. Specific research accomplishments in the past year include the following: (1) evaluation of the effects of proteasome inhibitor treatment in a mouse model of SMA, (2) characterization of the effects of IGF-1 in an animal model of SBMA,(3) identification of interacting proteins for wild type and mutant ZASP and developing animal models with ZASP mutation.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
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; SorarĂº, 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

Showing the most recent 10 out of 51 publications