Research in the Davidson
Research in my
laboratory is focused on inherited genetic diseases that
cause central nervous system dysfunction,
with a focus on (1) recessive, childhood
neurodegenerative disease, in particular the lysosomal storage diseases
such as the mucopolysaccharidoses and Battens disease; and (2) dominant genetic diseases for example the
CAG repeat disorders, Huntington’s disease and spinal cerebellar ataxia
type I, and (3), understanding how
noncoding RNAs participate in neural
development and neurodegenerative diseases processes.
Our research on
childhood onset neurodegenerative diseases is focused on experiments to
better understand the biochemistry and cell biology of proteins
deficient in these disorders, and to develop gene small molecule based
medicines for therapy. In recent work we demonstrated that the
application of recombinant viral vectors to animal models of storage
disease reversed CNS deficits.
dominant disorders are an exciting challenge and require that the
dominant disease allele be silenced. To approach this, we developed
reagents for expressing inhibitory RNA in vivo. This approach improved
disease phenotypes in relevant models of dominantly inherited human
investigate how naturally occurring noncoding RNAs, miRNAs, participate
in cell fate decisions in normal
development, and how their expression
is altered in disease states. We find that miRNAs with altered
expression in Huntington’s disease or spinocerebellar ataxia brains
target proteins that themselves contribute to disease phenotypes. This
work may reveal new targets for drug therapy.
Purkinje cell miRNA expression and SCA1 pathogenesis.
Rodriguez-Lebron E, Liu G, Keiser M, Behlke MA, Davidson BL. Neurobiol
Dis. 2013 Jan 30. (Abstract)
tool for designing highly specific and potent siRNAs for human and
mouse. Boudreau RL, Spengler RM, Hylock RH, Kusenda BJ, Davis
HA, Eichmann DA, Davidson BL. Nucleic Acids Res. 2013 Jan 7;41(1) (Abstract)
required for proliferation, viability, migration and differentiation in
corticoneurogenesis. McLoughlin HS, Fineberg SK, Ghosh LL,
Tecedor L, Davidson BL. Neuroscience. 2012 Oct 25;223:285-95. (Abstract)
represses Numbl in murine neural progenitor cells and antagonizes
neuronal differentiation. Fineberg SK, Datta P, Stein CS,
Davidson BL. PLoS One. 2012;7(6). (Abstract)
deposition impairs the utility of AAV9, but not peptide-modified AAVs
for brain gene therapy in a mouse model of lysosomal storage disease.
Chen YH, Claflin K, Geoghegan JC, Davidson BL. Mol Ther. 2012
of hairpin-based RNAi vectors for biological and therapeutic
application. Boudreau RL, Davidson BL. Methods Enzymol.
safety of RNAi-mediated HTT suppression in the rhesus macaque as a
potential therapy for Huntington's disease. McBride JL, Pitzer
MR, Boudreau RL, Dufour B, Hobbs T, Ojeda SR, Davidson BL. Mol Ther.
2011 Dec;19(12):2152-62. (Abstract)
design of therapeutic siRNAs: minimizing off-targeting potential to
improve the safety of RNAi therapy for Huntington's disease.
Boudreau RL, Spengler RM, Davidson BL. Mol Ther. 2011
lysosomal storage diseases. Schultz ML, Tecedor L, Chang M,
Davidson BL. Trends Neurosci. 2011 Aug;34(8):401-10. (Abstract)