The research in the Han Lab is directed to understand the molecular mechanisms of genetic diseases affecting the neuromuscular system, and to develop novel therapeutic strategies to combat these devastating diseases.
Dystrophin deficiency causes Duchenne muscular dystrophy. In our recent work published in Cell and Bioscience, we reported that a porcine model of DMD generated by CRISPR gene editing developed muscular dystrophy, cardiomyopathy and gastrointestinal tract dysfunction. Malnutrition may further exacerbate skeletal and cardiac muscle pathology. Read the article here ...
Base editing holds great potential to correct mutations causing genetic myopathies. In our recent work published in Nature Communications, we demonstrated that a single intravenous administration of AAV9 delivered base editor rescued dystrophin expression in over 95% cardiomyocytes in adult dystrophic mice. Read the article here ...
CRISPR geome editing is a powerful too. In a paper published in Oncogene, we showed that genome-wide CRISPR screen identifies LGALS2 as an oxidative stress-responsive gene with an inhibitory function on colon tumor growth. Read more ...
In our paper published in Molecular Therapy, we developed a fluorescence reporter to rapidly quantify and enrich adenine base editing events. Together with our recent BEAT program published in CRISPR J, it offers a rapid, inexpensive and quantitative approach to study adenine base editing. Read more ...
We reported in the Molecular Therapy paper that AAVrh74 delivered CRISPR to delete the mutant exons in a dystrophic mouse model exhibited a good safety profile. Read more ...
The mouse models of DMD do not recapitulate many aspects of human DMD. We have thus generated a rabbit model of DMD, which show many similarities to their human counterparts, such as muscular dystrophy, cardiomyopathy, shortened lifespan, hindlimb paralysis etc. This work is published in Disease Models & Mechanisms Read more ...
In this study published in Circulation Research, we showed that systemic AAVrh74-CRISPR delivery enables the restoration of dystrophin expression and cardiac function in a mouse model of DMD, mdx/utrophin+/- mice. Read more ...
Simultaneous editing of multiple genes is required in many applications. In this study published in Nucleic Acids Research, we developed a system to enable multiplex genome editing via simultaneous expression of multiple guide RNAs from a single transcript mediated by self-cleaving ribozymes and tRNAs. Read more ...
We reported for the first time that in vivo CRISPR-gene editing in postnatal animals is feasible. In this study published in Molecular Therapy, we demonstrated that adenovirus-mediated delivery of CRISPR restored dystrophin expression and improved muscle function. Read more ...
Oxidative stress is known to cause NLRP3 inflammasome activation, but the signaling pathway linking oxidative stress to NLRP3 inflammasome activation was obscure. In this study published in Nature Medicine, we demonstrated that a non-selective Ca2+ channel TRPM2 is a critical mediator. Read more ...