Research Overview

Research in the Davidson Laboratory is focused on inherited genetic diseases that cause central nervous system dysfunction, with a focus on (1) recessive, childhood onset neurodegenerative disease, such as the lysosomal storage diseases mucopolysaccharidoses and Battens disease; (2) dominant genetic diseases, specifically the CAG repeat disorders, Huntington’s disease and spinal cerebellar ataxia; and (3), understanding how changes in the transcriptome impact neural development and neurodegenerative disease 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 small molecule or gene therapy based strategies for therapy. In recent work, we demonstrated that the application of recombinant viral vectors to various models of storage disease reversed CNS deficits and improved life span. We continue to develop novel vector systems to improve therapeutic outcomes.

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 RNAs or editing machinery (e.g., CrispR/Cas9 approaches) in vivo to improve disease phenotypes in relevant animal models.

Finally, we investigate how the transcriptome is altered in neurological diseases. Evaluation of splicing changes has led us to discover novel players in disease pathogenesis that include noncoding RNAs and RNA binding proteins. This work is revealing new pathways of pathogenesis and novel targets for therapy.

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Most Recent Publications:

CRISPR/Cas9 Editing of the Mutant Huntingtin Allele In Vitro and In vivo
Monteys AM, Ebanks SA, Keiser MS, Davidson BL.
Molecular Therapy 2017 Jan 05. doi: 10.1016/j.ymthe.2016.11.010 (Full text)

RNAi prevents and reverses phenotypes induced by mutant human ataxin-1.
Keiser MS, Monteys AM, Corbau R, Gonzalez-Alegre P, Davidson BL.
Ann Neurol. 2016 Sep 30. doi: 10.1002/ana.24789 (Abstract)

Cis-Acting Single Nucleotide Polymorphisms Alter MicroRNA-Mediated Regulation of Human Brain-Expressed Transcripts.
Ramachandran S, Coffin SL, Tang TY, Jobaliya CD, Spengler RM, Davidson BL.
Hum Mol Genet. 2016 Sep 16. pii: ddw317 (Abstract)

Transcriptome sequencing reveals aberrant alternative splicing in Huntington's disease.
Lin L, Park JW, Ramachandran S, Zhang Y, Tseng YT, Shen S, Waldvogel HJ, Curtis MA, Faull RL, Troncoso JC, Ross CA, Davidson BL, Xing Y.
Hum Mol Genet. 2016 Jul 4. pii: ddw187 (Abstract)

Elucidation of transcriptome-wide microRNA binding sites in human cardiac tissues by Ago2 HITS-CLIP.
Spengler RM, Zhang X, Cheng C, McLendon JM, Skeie JM, Johnson FL, Davidson BL, Boudreau RL
Nucleic Acids Res. 2016 Jul 14. pii: gkw640 (Abstract)

PIAS1 Regulates Mutant Huntingtin Accumulation and Huntington's Disease-Associated Phenotypes In Vivo.
Ochaba J, Monteys AM, O'Rourke JG, Reidling JC, Steffan JS, Davidson BL, Thompson LM.
Neuron. 2016 May 4;90(3):507-20 (Abstract)

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