Dr. Xu directs the Zebrafish Genetics Laboratory, which studies cardiac diseases using zebrafish as a vertebrate model. Dr. Xu's lab has generated the first embryonic and adult zebrafish models for cardiomyopathies.
By leveraging unique genetic tools offered by zebrafish, Dr. Xu and his colleagues are using these models to elucidate molecular mechanisms of cardiomyopathy and develop novel therapeutic strategies.
· Develop target of rapamycin (TOR)-based therapy for cardiomyopathy. Dr. Xu's laboratory characterized a zebrafish target of rapamycin (ztor) mutant fish and provided the first genetic evidence of a therapeutic effect of long-term TOR signaling inhibition on cardiomyopathy.
In collaboration with Mayo clinician-scientists, Dr. Xu's lab is working to translate this TOR-based therapy from bench to bedside. This is being done through projects aimed at elucidating the downstream signaling branches that confer the therapeutic effect of TOR signaling inhibition and screening new compounds of better therapeutic value than rapamycin.
· Elucidate an inhibitory mechanotransduction signaling pathway in cardiomyopathy. Dr. Xu's laboratory identified the transcriptional regulation of the Tcap gene as a stretch-induced signaling event during pathogenesis of cardiomyopathy. By leveraging both embryonic and adult zebrafish models, his lab aims to elucidate the underlying molecular mechanisms. The ultimate goal is to develop Tcap-based therapeutics for cardiomyopathy.
· Identify new genetic modifiers of cardiomyopathy via zebrafish genetics. By conducting a pilot transposon-based insertional mutagenesis screen, Dr. Xu's lab proved the feasibility of identifying cardiomyopathy modifiers via generating an adult zebrafish cardiac insertional mutant (ZIC) collection. His lab is expanding the ZIC collections to identify novel genes and signaling pathways that modify the pathogenesis of cardiomyopathy. The goal is to develop new therapeutic strategies based on these novel modifiers.
Significance to patient care
By generating cardiomyopathy models in zebrafish, Dr. Xu's lab aims to develop novel therapeutics for cardiomyopathy and heart failure based on molecular genetic studies in this model organism.