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Research Interests

DNA Repair

                Although diverse molecular and cellular biology studies have revealed numerous biological mechanisms involved in DNA damage responses and repair processes, understanding the roles of DNA repair genes at the level of the entire organisms remains limited. Zebrafish is a powerful genetic model system allowing for an array of diverse experimental approaches including large-scale forward screening and gene-editing through CRISPR targeting. Taking advantage of this model system, we generated multiple loss-of-function animals using high-throughput CRISPR mutagenesis. We obtained around 40 mutants of DNA repair genes and have continuously characterized the phenotypes of embryos and adult animals. Using these experimental tools, we will explore the in vivo roles and functions of DNA repair genes during development and eventually analyze the correlation of their functions with human genetic diseases.

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Hematopoiesis

               Hematopoietic stem cells (HSCs) are multipotent progenitors of blood cells that self-renew and differentiate into all mature blood lineages. Therefore, strict control of the temporal and spatial specification, maturation, and expansion of HSCs is crucial for the normal function of the blood and immune system. HSCs arise from the hemogenic endothelium, a special population of endothelial cells within the ventral wall of the dorsal aorta that transdifferentiate into HSCs. Our studies are aimed at understanding how HSCs are specified. We performed forward genetic screen using zebrafish embryos to find novel genes required for HSC specification, obtaining multiple mutants, which failed to form HSCs in the aorta. We are currently characterizing the mutant phenotypes and are mapping and positionally cloning genes, which cause the defects of HSC formation. Our studies will provide insight into the molecular cues that specify HSCs.

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