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.

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Pourshafie, Naemeh; Lee, Philip R; Chen, Ke-Lian et al. (2016) MiR-298 Counteracts Mutant Androgen Receptor Toxicity in Spinal and Bulbar Muscular Atrophy. Mol Ther 24:937-45
Fischbeck, Kenneth H (2016) Spinal and Bulbar Muscular Atrophy Overview. J Mol Neurosci 58:317-20
Hjelm, B E; Grunseich, C; Gowing, G et al. (2016) Mifepristone-inducible transgene expression in neural progenitor cells in vitro and in vivo. Gene Ther 23:424-37
Bott, Laura C; Salomons, Florian A; Maric, Dragan et al. (2016) The polyglutamine-expanded androgen receptor responsible for spinal and bulbar muscular atrophy inhibits the APC/C(Cdh1) ubiquitin ligase complex. Sci Rep 6:27703
Foran, Emily; Kwon, Deborah Y; Nofziger, Jonathan H et al. (2016) CNS uptake of bortezomib is enhanced by P-glycoprotein inhibition: implications for spinal muscular atrophy. Neurobiol Dis 88:118-24
Bott, Laura C; Badders, Nisha M; Chen, Ke-Lian et al. (2016) A small-molecule Nrf1 and Nrf2 activator mitigates polyglutamine toxicity in spinal and bulbar muscular atrophy. Hum Mol Genet 25:1979-1989
Scaramuzzino, Chiara; Casci, Ian; Parodi, Sara et al. (2015) Protein arginine methyltransferase 6 enhances polyglutamine-expanded androgen receptor function and toxicity in spinal and bulbar muscular atrophy. Neuron 85:88-100
Pripuzova, Natalia S; Getie-Kebtie, Melkamu; Grunseich, Christopher et al. (2015) Development of a protein marker panel for characterization of human induced pluripotent stem cells (hiPSCs) using global quantitative proteome analysis. Stem Cell Res 14:323-38
Bricceno, Katherine V; Martinez, Tara; Leikina, Evgenia et al. (2014) Survival motor neuron protein deficiency impairs myotube formation by altering myogenic gene expression and focal adhesion dynamics. Hum Mol Genet 23:4745-57
Renvoisé, Benoît; Chang, Jaerak; Singh, Rajat et al. (2014) Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11. Ann Clin Transl Neurol 1:379-389

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