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.