Research in the Davidson Laboratory

Dr. Davidson:


Research in my laboratory is focused on inherited genetic diseases that cause central nervous system dysfunction, with a focus on (1) recessive, childhood onset 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.



Rodriguez et al, Neurobiol Dis. 2013 Jan 30.

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.

Therapies for 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 neurodegenerative diseases.


Finally, we 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.

Next topic

Altered Purkinje cell miRNA expression and SCA1 pathogenesis. Rodriguez-Lebron E, Liu G, Keiser M, Behlke MA, Davidson BL. Neurobiol Dis. 2013 Jan 30. (Abstract)

siSPOTR: a 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)

Dicer is 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)

MiR-34a 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)

Sialic acid 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 Jul;20(7):1393-9. (Abstract)

Generation of hairpin-based RNAi vectors for biological and therapeutic application. Boudreau RL, Davidson BL. Methods Enzymol. 2012;507:275-96. (Abstract)

Preclinical 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)

Rational 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 Dec;19(12):2169-77. (Abstract)

Clarifying lysosomal storage diseases. Schultz ML, Tecedor L, Chang M, Davidson BL. Trends Neurosci. 2011 Aug;34(8):401-10. (Abstract)