We are interested in generating next-generation mouse models and novel therapeutics. Our primary focus is to develop and validate novel tools/reagents for rapid generation of mouse models of human disease using CRISPR/Cas9 and Integrase systems, identify genetic modifiers, and to treat the underlying cause of the disease.
Development of state-of-the-art technologies is essential to precisely and rapidly generate and characterize mouse models of human disease. Since 2015 we have been utilizing advanced genetic engineering technology, including CRISPR/Cas9 and Bxb1 recombinases to uncover several major findings: a) Gene disruption in mouse embryonic stem cells or zygotes is a conventional genetics approach to identify gene function in vivo. However, because different gene disruption strategies use different mechanisms to disrupt genes, the strategies can result in diverse phenotypes in the resulting mouse model. To determine whether different gene disruption strategies affect the phenotype of resulting mutant mice, we characterized Rhbdf1 mouse mutant strains generated by three commonly used strategies—definitive-null, targeted knockout (KO)-first, and CRISPR/Cas9. we found that Rhbdf1 responds differently to distinct KO strategies, for example, by skipping exons and reinitiating translation to potentially yield gain-of-function alleles rather than the expected null or severe hypomorphic alleles. These findings have significant implications for the application of genome editing in both basic research and clinical practice, b) Mice have been excellent surrogates for studying immune system and, moreover, murine models of human disease have provided fundamental insights into the roles of human macrophages and neutrophils in innate immunity. The emergence of novel humanized mice and high-diversity mouse populations offers the research community innovative and powerful platforms for better understanding the mechanisms by which human innate immune cells drive pathogenicity. We have been developing advanced genetic engineering tools, including Bxb1 recombinase system, sophisticated profiling technologies, and nanoparticle (NP)-based-targeting strategies to understand how genetic differences underpin the variation in macrophage/neutrophil biology observed among humans.
NCI funded Postdoc positions available
We are looking for a brilliant and self-motivated individuals to join our team to generate and validate humanized mouse models of cancer using novel gene-editing technologies. This position is ideally suited for an individual with a strong background in molecular biology (CRISPR/Cas9) and next-generation sequencing methods. Exceptional candidates can show early independence through the JAX Scholars Program.