Research

Understanding the mechanisms of muscular dystrophies

Our research is centered on elucidating the molecular and cellular mechanisms underlying various muscular dystrophies. Our previous work revealed that muscular dystrophies (MDs) could arise from defects in two important mechanisms involved in maintaining the plasma membrane integrity (J Clin Invest, 2007; PNAS, 2009; J Clin Invest, 2010). We are currently investigating the molecular and cellular function of anoctamin 5, which is associated with several human diseases including Limb girdle muscular dystrophy type 2L (Skelet Muscle, 2015; J Pathol Clin Res, 2018).

Developing genome editing therapies for DMD

CRISPR has been harnessed as a novel platform for genome editing. We and others have pioneered a novel CRISPR genome editing therapy for Duchenne muscular dystrophy (DMD) (Mol Ther, 2015; Circ Res 2017; Nucleic Acid Res 2017; Mol Ther 2019). This therapeutic strategy utilizes CRISPR genome editing to slice out the mutant exons or disrupt the splicing sites to skip the mutant exons, so that dystrophin reading frame is restored. This has shown great promise in murine and canine models of DMD.

Establishing novel rabbit models of MDs

Genetic animal models are essential for us to understand the pathophysiology and to develop therapeutic strategies for various diseases. However, translation from the findings obtained in mouse models of MDs to patients has been poor. Therefore, we are developing novel animal models using rabbits. Recently, we have successfully generated rabbit models for DMD and Ano5 (Cell Death Dis, 2018; Dis Model Mech, 2018). We envision that these new models would facilitate the basic and translational studies of muscular dystrophy.