研究组主要以小鼠为模型，通过细胞示踪、基因敲除、高通量筛选、以及常规的分子生化实验，研究肝细胞异质性在肝脏稳态维持及疾病发生过程中的作用，重点关注细胞在响应内在基因突变及外在环境改变时的功能调整及命运抉择。期望通过调控基因在不同时空的表达影响细胞命运，促进肝脏正常再生，阻断肝疾病及肝癌的发生。

具体研究方向：

1. 细胞异质性在肝脏稳态维持、损伤修复及癌变过程中的作用；

2. 物质代谢与肝疾病的联系；

3. 肝细胞与微环境的互作，以及这些互作在肝疾病中的作用。

1. Wei YL, Wang Y G, Jia YM, Li L, Yoon J, Zhang SY, Wang ZX, Zhang Y, Zhu M, Sharma T, Lin YH, Hsieh MH, Albrecht J. H, Le P.T, Rosen C.J, Wang T and Zhu H. Liver homeostasis is maintained by midlobular zone 2 hepatocytes. Science 371(6532): eabb1625, (2021).

2. Wei YL, Xu J, Zhang WQ, Wen Z, and Liu F. RNA polymerase III component Rcp9 regulates hematopoietic stem and progenitor cell maintenance in zebrafish. Development. 143(12):2103-2110, (2016).

3. Wei YL, Ma DY, Gao Y, Zhang CX, Wang L, Liu F. Ncor2 is required for hematopoietic stem cell emergence by inhibiting Fos signaling in zebrafish. Blood. 124(10):1578-85, (2014).

4. Hu, SQ, Fang Y, Chen X, Cheng TL, Zhao MQ, Du MJ, Li T, Li MH, Zeng ZQ, Wei YL, Gu ZM, Zhang CG, Sun LJ and Chen Z J. "cGAS restricts colon cancer development by protecting intestinal barrier integrity." Proc Natl Acad Sci U S A. 118(23), (2021).

5. Cheng Q, Wei T, Jia YM, Farbiak L, Zhou KJ, Zhang SY, Wei YL, Zhu H, Siegwart D.J. Dendrimer‐based lipid nanoparticles deliver therapeutic FAH mRNA to normalize liver function and extend survival in a mouse model of hepatorenal tyrosinemia type I. Adv Mater30(52): p. e1805308, (2018).

6. Sun XX, Wang SC, Wei YL, Luo X, Jia YM, Li L, Gopal P, Zhu M, Nassour I, Chuang JC, Maples T, Celen C, Nguyen LH, Singal AG and Zhu H et. al. "Arid1a Has Context-Dependent Oncogenic and Tumor Suppressor Functions in Liver Cancer." Cancer Cell 32(5): 574-589, (2017)

7. Liu XJ, Wei YL, Li YN, Li HY, Yang X, Yi YZ and Zhang ZF "A highly efficient and simple construction Strategy for producing recombinant Baculovirus Bombyx mori nucleopolyhedrovirus." PLoS One 11(3): e0152140, (2016).

8. Lu XY, Wei YL, Liu F. Direct regulation of p53 by miR-142a-3p mediates the survival of hematopoietic stem and progenitor cells in zebrafish. Cell Discovery, doi:10.1038/celldisc.2015.27.5.

9. Wang L, Liu TH, Xu LJ, Gao Y, Wei YL, Duan C, Chen GQ, Lin S, Patient R, Zhang B, Hong DL, Liu F. Fev regulates hematopoietic stem cell development via ERK signaling. Blood. 122(3):367-75, (2013).

10. Ma DY#, Wei YL#, Liu F. Regulatory mechanisms of thymus and T cell development. Dev Comp Immunol.39(1-2):91-102, (2013) (#Equal contributors).

11. Ma DY, Wang L, Wang SF, Gao Y, Wei YL, Liu F. Foxn1 maintains thymic epithelial  cells to support T-cell development via mcm2 in zebrafish. Proc Natl Acad Sci U S A. 109(51):21040-5, (2012).

12. Wang L, Zhang PP, Wei YL, Gao Y, Patient R, Liu F. A blood flow-dependent klf2a-NO signaling cascade is required for stabilization of hematopoietic stem cell programming in zebrafish embryos. Blood. 118(15):4102-10, (2011).

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