范衡宇

范衡宇博士，浙江大学生命科学研究院教授、研究员、博士生导师。办公地点位于医学院科研楼A305，电话0571-88981582，邮箱hyfan@zju.edu.cn。实验室网站：http://lsi.zju.edu.cn/yjdw_detail.aspx?ID=8。 ADFASDFAF23RQ23R

• 1993-1997：东北农业大学生物工程系，学士
• 1997-2000：东北农业大学生命科学学院，动物组织胚胎学硕士
• 2000-2003：中国科学院动物研究所，生殖生物学博士
• 2003-2006：美国德克萨斯大学西南医学中心（UTSW）分子生物学系，博士后
• 2006-2009：美国贝勒医学院（Baylor College of Medicine）分子与细胞生物学系，博士后
• 2010-至今：浙江大学生命科学研究院教授，研究员，博士生导师

• 2003：中国科学院院长优秀奖
• 2009：Ruth L. Kirschstein National Research Service Award, National Institute of Health, USA
• 2009：Lalor Foundation Merit Award
• 2007-至今：Membership of the Society for the Study of Reproduction

本实验室主要研究哺乳动物卵巢功能的分子调节机理以及卵巢相关疾病的发生机理。卵巢作为雌性生殖器官，其功能主要是产生成熟的雌性生殖细胞（卵母细胞）并分泌性激素。哺乳动物卵巢主要由处于不同发育阶段的卵泡和黄体组成。卵泡的发育、排卵和黄体化受到两种促性腺激素FSH和LH的紧密调控。我们利用多种卵泡颗粒细胞或卵母细胞特异性的基因敲除小鼠和转基因小鼠，研究促性腺激素激活的信号通路及其靶基因对卵巢功能的调节作用。我们最近的研究揭示，PI3K/AKT信号通路参与调节颗粒细胞增殖或凋亡，而RAS/ERK1/2信号途径是LH诱导卵母细胞成熟、排卵和黄体化过程所必需的。通过基因芯片分析，我们鉴定出了小鼠基因组中所有在排卵过程中受到LH调节的基因，并进一步确定了哪些LH靶基因的表达依赖于RAS/ERK1/2信号通路的激活。在进一步的研究中，我们将继续分析这些新发现的LH靶基因在卵巢中的功能，以及其他重要信号通路对卵泡发育和排卵的调节作用。

当这些调节卵巢正常功能的信号分子发生遗传缺失或过度激活，就会导致各种卵巢疾病，比如卵巢早衰、多囊卵巢综合症和卵巢肿瘤。本实验室也将综合利用转基因小鼠模型和人类临床样本，研究重要基因和信号通路在这些卵巢疾病发生中的作用。

上述工作，不仅可以推动哺乳动物生殖与发育生物学的基础研究，也在医学临床实践（如辅助生殖、计划生育、内分泌疾病和卵巢癌的治疗）、经济动物养殖和珍稀野生动物保护等领域具有重要的理论指导作用。 ADSFAEQWER353423413434

1. Fan HY, O'Connor A, Shitanaka M, Shimada M, Liu Z, Richards JS. Beta-catenin (CTNNB1) promotes preovulatory follicular development but represses luteinizing hormone-mediated ovulation and luteinization. Molecular Endocrinology, 2010 (me.2010-0141).
2. Liu Z, Fan HY, Wang Y, Richards JS. Targeted disruption of MAPK14 (p38MAPK alpha) in granulosa cells and cumulus cells causes cell specific and compensatory changes in gene expression profiles that maintain fertility in vivo. Molecular Endocrinology, 2010 (me.2010-0138).
3. Fan HY, Richards JS. Physiological and pathological actions of RAS in the ovary. Molecular Endocrinology, 2010, 24:286-298.
4. Fan HY, Liu Z, Paquet M, Wang J, Lydon JP, DeMayo FJ, Richards JS. Cell type-specific targeted mutations of Kras and Pten document proliferation arrest in granulosa cells versus oncogenic insult to ovarian surface epithelial cells. Cancer Research, 2009, 69:6463-6472.
5. Fan HY, Liu Z, Shimada M, Sterneck E, Johnson PF, Hedrick SM, Richards JS. MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science, 2009, 324:938-941.
6. Sun Y, Kucej M, Fan HY, Yu H, Sun QY, Zou H. Separase is recruited to mitotic chromosomes to dissolve sister chromatid cohesion in a DNA-dependent manner. Cell, 2009, 137:123-132.
7. Liu Z, de Matos DG, Fan HY, Shimada M, Palmer S, Richards JS. Interleukin-6: an autocrine regulator of the mouse cumulus cell-oocyte complex expansion process. Endocrinology, 2009, 150(7):3360-3368.
8. Liu Z, Rudd MD, Hernandez-Gonzalez I, Gonzalez-Robayna I, Fan HY, Zeleznik AJ, Richards JS. FSH and FOXO1 regulate genes in the sterol/steroid and lipid biosynthetic pathways in granulosa cells. Molecular Endocrinology, 2009, 23:649-661.
9. Laguë MN, Paquet M, Fan HY, Kaartinen MJ, Chu S, Jamin SP, Behringer RR, Fuller PJ, Mitchell A, Doré M, Huneault LM, Richards JS, Boerboom D. Synergistic effects of Pten loss and WNT/CTNNB1 signaling pathway activation in ovarian granulosa cell tumor development and progression. Carcinogenesis, 2008, 29(11):2062-2072.
10. Fan HY, Liu Z, Cahill N, Richards JS. Targeted disruption of Pten in ovarian granulosa cells enhances ovulation and extends the life span of luteal cells. Molecular Endocrinology, 2008, 22(9):2128-2140.
11. Fan HY, Shimada M, Liu Z, Cahill N, Noma N, Wu Y, Gossen J, Richards JS. Selective expression of KrasG12D in granulosa cells of the mouse ovary causes defects in follicle development and ovulation. Development, 2008, 135:2127-2137.
12. Wayne CW, Fan HY, Cheng X, Richards JS. FSH induces multiple signaling cascades: evidence that activation of SRC, RAS and the EGF receptor are critical for granulosa cell differentiation. Molecular Endocrinology, 2007, 21:1940-1957.
13. Fan HY, Sun QY, Zou H. Regulation of separase in meiosis: separase is activated at the metaphase I-II transition in Xenopus oocytes during meiosis. Cell Cycle, 2006, 10:198-204.
14. Fan HY, Huo LJ, Schatten H, Chen DY, Sun QY. Protein kinase C and MAPK cascade in mouse cumulus cells: crosstalk and effect on meiotic resumption of oocyte. Biology of Reproduction, 2004, 70:1178-1187.
15. Fan HY, Sun QY. Involvement of mitogen-activated protein kinase cascade during oocyte maturation and fertilization in mammals. Biology of Reproduction, 2004, 70(3):535-547.
16. Tong C, Fan HY, Li SW, Chen DY, Schatten H, Song XF, Sun QY. Effects of MEK inhibitor U0126 on meiotic progression in mouse oocyte: microtubule organization, asymmetric division and metaphase II arrest. Cell Research, 2003, 13:375-383.
17. Fan HY, Tong C, Teng CB, Lian L, Li SW, Yang ZM, Chen DY, Schatten H, Sun QY. Characterization of Polo-like kinase-1 in rat oocytes and early embryos implies its functional roles in the regulation of meiotic maturation, fertilization and cleavage. Molecular Reproduction and Development, 2003, 65:318-329.
18. Fan HY, Huo LJ, Meng XQ, Zhong ZS, Hou Y, Chen DY, Sun QY. Involvement of calcium/calmodulin-dependent protein kinase II (CaMKII) in the meiotic maturation and activation of pig oocytes. Biology of Reproduction, 2003, 69:1552-1564.
19. Fan HY, Tong C, Lian L, Li SW, Gao WX, Cheng Y, Chen DY, Schatten H, Sun QY. Characterization of ribosomal S6 protein kinase p90rsk during meiotic maturation and fertilization in pig oocytes: MAPK-associated activation and localization. Biology of Reproduction, 2003, 68:968-977.
20. Tong C, Fan HY, Lian L, Li SW, Chen DY, Schatten H, Sun QY. Polo-like kinase 1 is a pivotal regulator of microtubule assembly during mouse oocyte meiotic maturation, fertilization, and early embryonic mitosis. Biology of Reproduction, 2002, 67:546-554.
21. Fan HY, Li MY, Tong C, Chen DY, Xia GL, Song XF, Schatten H, Sun QY. Inhibitory effects of cAMP and protein kinase C on meiotic maturation and MAP kinase phosphorylation in porcine oocytes. Molecular Reproduction and Development, 2002, 63:480-487.
22. Fan HY, Tong C, Li MY, Lian L, Chen DY, Schatten H, Sun QY. Translocation of classical protein kinase C (cPKC) isoforms in porcine oocytes: implications of PKC involvement in the regulation of nuclear activity and cortical granule exocytosis. Experimental Cell Research, 2002, 277:183-191.

• Fan HY, O'Connor A, Shitanaka M, et al. Beta-catenin (CTNNB1) promotes preovulatory follicular development but represses luteinizing hormone-mediated ovulation and luteinization. Molecular Endocrinology, 2010.
• Fan HY, Liu Z, Paquet M, et al. Cell type-specific targeted mutations of Kras and Pten document proliferation arrest in granulosa cells versus oncogenic insult to ovarian surface epithelial cells. Cancer Research, 2009, 69:6463-6472.
• Fan HY, Liu Z, Shimada M, et al. MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science, 2009, 324:938-941.
• Sun Y, Kucej M, Fan HY, et al. Separase is recruited to mitotic chromosomes to dissolve sister chromatid cohesion in a DNA-dependent manner. Cell, 2009, 137:123-132.
• Fan HY, Richards JS. Physiological and pathological actions of RAS in the ovary. Molecular Endocrinology, 2010, 24:286-298.
• Fan HY, Liu Z, Cahill N, Richards JS. Targeted disruption of Pten in ovarian granulosa cells enhances ovulation and extends the life span of luteal cells. Molecular Endocrinology, 2008, 22(9):2128-2140.
• Zhang Y, Wang Y, Sun QY, et al. The role of PI3K/AKT signaling in ovarian follicle development. Frontiers in Cell and Developmental Biology, 2021, 9:678943.
• Chen X, Liu J, Li Y, et al. Advances in understanding the molecular mechanisms of ovulation. Reproduction, 2020, 160(2):R1-R13.
• 范衡宇, 孙青原. 哺乳动物卵母细胞成熟过程中MAPK级联信号通路的研究进展. 动物学报, 2004, 50(2):305-312.
• 刘忠华, 范衡宇, 陈大元. 卵母细胞减数分裂的分子调控. 中国科学基金, 2005, 19(4):206-210.