I lead multiple projects including: Screening small compounds to boost AAV production; Tissue-specific promoter engineering; In Vitro VCN assay development etc.

I am a Postdoc at UCSF studying the developmental disorders of lung, heart, and small intestine in mouse models. These are great extensions of my knowledge and skill in addition to my previous experience in genetic disorders. Genes are expressed in various tissues but their mutations usually cause phenotypes in a tissue-specific manner. And the roles and mechanisms of some genes can be different in different tissues. Also, different mutations of the same gene can cause different phenotypes. This is interesting as it challenges the models of uniformly consistent roles and mechanisms of genes. I'm interested in bridging in vitro biology to in vivo, unveiling the specificity among different tissues, and improving our understanding of life.

I worked on the PRKAG2 cardiac syndrome and used AAV9-CRISPR to specifically inactivate the gain-of-function mutant allele. This strategy has been proved effective in mouse models. It's very exciting as traditional gene therapies can't shut down the hyperactive genes. And CRISPR can discriminate single-base mutations, which is common in most genetic inherited diseases!I also worked on Niemann-Pick Type C (NPC) disease in mouse models. This is a typical loss-of-function genetic disease caused by mutations in NPC1 or NPC2. It's a lysosomal storage disorder and affects multiple tissues including the central nervous system, lung, liver. kidney, spleen, etc. It's also listed as a neurodegenerative disease. It's perfectly fit for traditional gene therapy: deliver the functional cDNA via AAV. Actually, AAV-based gene therapy is the most direct, effective, specific treatment with much less side effect. I also designed the gene therapy strategy to treat Danon disease, which is caused by X-linked Lamp2 mutation.

We identified H530R mutation of PRKAG2 from a family with WPW heart syndrome. And confirmed the mutation as the cause of the cardiac disease by generating heart specific transgenic mice and single mutation knock-in mutant mice. In order to cure the dominant inherited diesease, I tried the CRISPR/Cas9 genome editing system. By selecting the specific guide RNA, I was able to target and inactivate the mutant allele specifically. This strategy has been proven effective in mouse models of the PRKAG2 cardiac syndrome.I Identified bile acids analogues that are able to mobilize cholesterol and alleviate the symptoms in livers of NPC mice. I designed gene therapies to treat NPC disease. The most effective 2-HP-beta-cyclodextrin treatment showed inevitable adverse effects including hearing loss. Gene therapies are direct and less toxic.