范衡宇，男，浙江大學(xué)生命科學(xué)研究院教授、研究員、博士生導(dǎo)師。

教育和工作背景：1993-1997：東北農(nóng)業(yè)大學(xué)生物工程系 學(xué)士

1997-2000：東北農(nóng)業(yè)大學(xué)生命科學(xué)學(xué)院 動(dòng)物組織胚胎學(xué)碩士

2000-2003：中國科學(xué)院動(dòng)物研究所 生殖生物學(xué)博士

2003-2006：美國德克薩斯大學(xué)西南醫(yī)學(xué)中心（UTSW）分子生物學(xué)系博士后

2006-2009：美國貝勒醫(yī)學(xué)院（Baylor College of Medicine）分子與細(xì)胞生物學(xué)系博士后

2010-至今： 浙江大學(xué)生命科學(xué)研究院教授，研究員，博士生導(dǎo)師

本實(shí)驗(yàn)室主要研究哺乳動(dòng)物卵巢功能的分子調(diào)節(jié)機(jī)理以及卵巢相關(guān)疾病的發(fā)生機(jī)理。

卵巢作為雌性生殖器官，其功能主要是產(chǎn)生成熟的雌性生殖細(xì)胞（卵母細(xì)胞）并分泌性激素。哺乳動(dòng)物卵巢主要由處于不同發(fā)育階段的卵泡和黃體組成。卵泡的發(fā)育、排卵和黃體化受到兩種促性腺激素FSH和LH的緊密調(diào)控。我們利用多種卵泡顆粒細(xì)胞或卵母細(xì)胞特異性的基因敲除小鼠和轉(zhuǎn)基因小鼠，研究促性腺激素激活的信號(hào)通路及其靶基因?qū)β殉补δ艿恼{(diào)節(jié)作用。我們最近的研究揭示，PI3K/AKT信號(hào)通路參與調(diào)節(jié)顆粒細(xì)胞增殖或凋亡，而RAS/ERK1/2信號(hào)途徑是LH誘導(dǎo)卵母細(xì)胞成熟、排卵和黃體化過程所必需的。通過基因芯片分析，我們鑒定出了小鼠基因組中所有在排卵過程中受到LH調(diào)節(jié)的基因，并進(jìn)一步確定了哪些LH靶基因的表達(dá)依賴于RAS/ERK1/2信號(hào)通路的激活。在進(jìn)一步的研究中，我們將繼續(xù)分析這些新發(fā)現(xiàn)的LH靶基因在卵巢中的功能，以及其他重要信號(hào)通路對(duì)卵泡發(fā)育和排卵的調(diào)節(jié)作用。

當(dāng)這些調(diào)節(jié)卵巢正常功能的信號(hào)分子發(fā)生遺傳缺失或過度激活，就會(huì)導(dǎo)致各種卵巢疾病，比如卵巢早衰、多囊卵巢綜合癥和卵巢腫瘤。本實(shí)驗(yàn)室也將綜合利用轉(zhuǎn)基因小鼠模型和人類臨床樣本，研究重要基因和信號(hào)通路在這些卵巢疾病發(fā)生中的作用。

上述工作，不僅可以推動(dòng)哺乳動(dòng)物生殖與發(fā)育生物學(xué)的基礎(chǔ)研究，也在醫(yī)學(xué)臨床實(shí)踐（如輔助生殖、計(jì)劃生育、內(nèi)分泌疾病和卵巢癌的治療）、經(jīng)濟(jì)動(dòng)物養(yǎng)殖和珍稀野生動(dòng)物保護(hù)等領(lǐng)域具有重要的理論指導(dǎo)作用。

2002：中國科學(xué)院動(dòng)物研究所 優(yōu)秀研究生獎(jiǎng)　　2003：中國科學(xué)院 院長優(yōu)秀獎(jiǎng)　　2009：美國國立衛(wèi)生研究院 杰出研究獎(jiǎng)學(xué)金 (Ruth L. Kirschstein National Research Service Award, National Institute of Health, USA).　　2009：北美生殖生物學(xué)會(huì) 優(yōu)秀研究獎(jiǎng) (Lalor Foundation Merit Award)　　2010：國際卵巢生物學(xué)會(huì) 杰出青年科學(xué)家獎(jiǎng)　　2010：浙江省 杰出青年基金獲得者

　　1）早期研究集中在蛋白激酶在哺乳動(dòng)物卵母細(xì)胞減數(shù)分裂和受精中的作用。利用小鼠、大鼠和豬卵母細(xì)胞為實(shí)驗(yàn)?zāi)Ｐ�，提出蛋白激酶C亞型調(diào)節(jié)卵皮質(zhì)顆粒釋放，Polo-like激酶和鈣調(diào)蛋白依賴的蛋白激酶參與調(diào)節(jié)卵母細(xì)胞減數(shù)分裂，促性腺激素通過激活MAPK誘導(dǎo)卵母細(xì)胞減數(shù)分裂成熟。相關(guān)文章在Biology of Reproduction, Cell Cycle, Experimental Cell Research等國際主流期刊上發(fā)表，并獲得中國科學(xué)院院長優(yōu)秀獎(jiǎng)和中國科學(xué)院動(dòng)物研究所優(yōu)秀研究生等榮譽(yù)。　　2）最早克隆了模式生物非洲爪蟾的Separase基因，并研究了該基因在減數(shù)分裂染色體分離過程中的作用，以及細(xì)胞周期過程中Separase蛋白酶活性的調(diào)節(jié)機(jī)制。　　3）近年來，建立了卵巢顆粒細(xì)胞特異性的基因敲除小鼠模型，并成功應(yīng)用該技術(shù)研究了多個(gè)重要信號(hào)轉(zhuǎn)導(dǎo)分子和癌基因在卵巢中的功能。發(fā)現(xiàn)促性腺激素通過激活小G蛋白R(shí)AS和蛋白激酶ERK1/2，誘導(dǎo)卵母細(xì)胞成熟、排卵和黃體形成。用基因芯片技術(shù)篩選出小鼠基因組中所有受促性腺激素和ERK1/2調(diào)節(jié)的排卵相關(guān)基因，并用條件基因敲除技術(shù)證明C/EBP beta是卵巢顆粒細(xì)胞中重要的ERK1/2下游靶基因。通過這些研究，建立了促性腺激素誘導(dǎo)排卵的關(guān)鍵信號(hào)轉(zhuǎn)導(dǎo)網(wǎng)絡(luò)和基因表達(dá)譜�！　�4）在卵巢癌相關(guān)基因的研究中，發(fā)現(xiàn)抑癌基因PETN在調(diào)節(jié)卵泡生長、卵泡閉鎖、排卵數(shù)目和黃體細(xì)胞壽命等方面具有重要作用。發(fā)現(xiàn)癌基因KrasG12D 誘導(dǎo)卵泡發(fā)育異常，導(dǎo)致雌性動(dòng)物生殖力下降，發(fā)生卵巢早衰。建立了卵巢顆粒細(xì)胞癌和漿液性卵巢上皮細(xì)胞癌的小鼠模型，發(fā)現(xiàn)了PTEN和KrasG12D在誘導(dǎo)卵巢上皮細(xì)胞癌中的重要作用。

1. Fan HY, Liu Z, Mullany LK, Richards JS.Consequences of RAS and MAPK activation in the ovary: The good, the bad and the ugly.. 2012 ,356:74-79

2. Richards JS,Fan HY, Liu Z, Tsoi M, Laguë MN, Boyer A, Boerboom D.Either Kras activation or Pten loss similarly enhance the dominant-stable CTNNB1-induced genetic program to promote granulosa cell tumor development in the ovary and testis..2011,1u201317 【PDF download 】

3. Mullany LK,Fan HY, Liu Z, White LD, Marshall A, Gunaratne P, Anderson ML, Creighton CJ, Xin L, Deavers M, Wong KK, Richards JS.Molecular and functional characteristics of ovarian surface epithelial cells transformed by KrasG12D and loss of Pten in a mouse model in vivo.2011, 30:3522u20133536 【PDF download 】

4. Fan HY, Liu Z, Johnson PF, Richards JS.CCAAT/Enhancer binding proteins (C/EBP)-α and -β are essential for ovulation, luteinization and the expression of key target genes., 2011, 25(2): 253-268 【PDF download 】

5. Noma N, Kawashima I,Fan HY, Fujita Y, Kawai T, Tomoda Y, Mihara T, Richards JS, and Shimada M.LH-induced neuregulin 1 (NRG1) type III transcripts control granulosa cell differentiation and oocyte maturation., 2011 (1):104-16

6. Fan HY, Ou2019connor A, Shitanaka M, Shimada M, Liu Z, Richards JS.Beta-catenin (CTNNB1) promotes preovulatory follicular development but represses luteinizing hormone-mediated ovulation and luteinization., 2010, 24(8):1529-1542

7. Fan HY. BubR1, a spindle assembly checkpoint protein in mammalian oocyte meiosis.. 2010, 9(8):1458 【PDFDownload】

8. 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., 2010 24(9):1794-804

9. Fan HY, Richards JS. Physiological and pathological actions of RAS in the ovary., 2010,24:286-298 【PDF download 】

10. 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 【PDF download 】

11. 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. (Comment in:Science, 2009, 324:938-941., 2009, 361:718-719) 【PDF download】

12. 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., 2009, 137:123-132.

13. Liu Z, de Matos DG,Fan HY, Shimada M, Palmer S, Richards JS.(2009). Interleukin-6: an autocrine regulator of the mouse cumulus cell-oocyte complex expansion process.150(7): 3360-8. 【PDF download】

14. 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., 2009 23:649-661. 【PDF download】

15. 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., 2008, 29(11):2062-2072. 【PDF download 】

16. 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., 2008, 22(9):2128-2140. (Comment in Nature Medicine, 2008, 11:1192-1193.) 【PDF download 】

　　17. 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., 2008, 135:2127-2137.

　　18. Wayne CW,Fan HY,Cheng X, and Richards JS. FSH-induces multiple signaling cascades: evidence that activation of SRC, RAS and the EGF receptor are critical for granulosa cell differentiation., 2007, 21:1940-1957. 【PDF download 】

　　19. 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., 2006, 10:198-204

　　20. 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., 2004, 70:1178-1187 【PDF download 】

　　21. Fan HY, Sun QY. Involvement of mitogen-activated protein kinase Cascade during oocyte maturation and fertilization in mammals., 2004, 70(3):535-547 【PDF download 】

22. 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 itu2019s functional roles in the regulation of meiotic maturation and cleavage.Molecular Reproduction and Development, 2003 65:318-329

23. 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 【PDF download 】

24. 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., 2003, 68:968-977 【PDF download 】

　　25. Tong C,Fan HY, Lian L, Li SW, Chen DY, Schatten H, Sun QY. Polo-like kinase 1 is a pivotal regulator of micrutubule assembly during mouse oocyte meiotic maturation, fertilization, and early embryonic mitosis., 2002, 67:546-554 【PDF download 】

　　26. 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., 2002, 63: 480-487

　　27. 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., 2002, 277:183-191

28. Liang CG, Su YQ,Fan HY, Schatten H and Sun QY. Mechanisms regulating oocyte meiotic resumption: roles of mitogen-activated protein kinase., 2007, 21, 2037-2055

29. 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: microtuble organization, asymmetric division and metaphase II arrest., 2003, 13:375~383

30. Huo LJ,Fan HY, Zhong ZS, Schatten H, Chen DY, Sun QY. Involvement of ubiquitin-proteasome pathway in mouse oocyte meiotic maturation, fertilization and early embryonic cleavage., 2004 121(10):1275-1287

31. Huo LJ,Fan HY, Liang CG, Yu LZ, Zhong ZS, Schatten H, Chen DY, Sun QY. Regulation of ubiquitin-proteasome pathway on pig oocyte meiotic maturation and fertilization., 2004, 71(3):853-862

32. Cheng Y,Fan HY, Wen DC, Tong C, Zhu ZY, Lei L, Sun QY, Chen DY. Asynchronous cytoplast and karyoplast transplantation reveals that the cytoplasm determines the developmental fate of the nucleus in mouse oocytes., 2003 65:278~282

33. Yao LJ,Fan HY, Tong C, Chen DY, Sun QY. Polo-like kinase-1 in porcine oocyte meiotic maturation, fertilization and early embryonic mitosis., 2003, 49(3):399-405

34. Quan HM,Fan HY, Meng XQ, Huo LJ, Chen DY, Schatten H, Yang PM, Sun QY. Effects of PKC activation on the meiotic maturation, fertilization, and early embryonic development of mouse oocytes., 2003, 11 (4):329-337

35. Meng XQ,Fan HY, Zhong ZS, Zhang G, Li YL, Chen DY, Sun QY. Localization of gamma-tubulin in mouse eggs during meiotic maturation, fertilization, and early embryonic development., 2004, 50 (1):97-105.

36. Huo LJ, Yu LZ, Liang CG,Fan HY, Chen DY, Sun QY. Cell cycle-dependent subcellular localization of cyclin B1, phosphorylated cyclin B1 and p34cdc2 during oocyte meiotic maturation and fertilization in mouse.. 2005, 13(1):45-53.

37. Fan HY, Tong C, Chen DY, Sun QY. Roles of MAP kinase signaling pathway in meiosis of oocytes., 47:1157~1162

38. Fan HY, Tong C, Chen DY, Sun QY. Roles of protein kinase C in meiotic maturation and fertilization of oocytes., 2003, 13:401-406

39. 范衡宇，佟超，陳大元，孫青原：蛋白激酶在卵母細(xì)胞減數(shù)分裂成熟和受精中的作用。 生物化學(xué)與生物物理學(xué)報(bào)，2002，34: 259-265

40. 范衡宇，佟超，李滿玉，孫青原：用激光共聚焦顯微術(shù)在小鼠卵母細(xì)胞中檢測(cè)蛋白激酶C。生物化學(xué)與生物物理進(jìn)展，2001, 28: 900-903

41. 范衡宇，佟超，孫青原：核糖體S6蛋白激酶p90rsk與卵母細(xì)胞減數(shù)分裂。生物化學(xué)與生物物理進(jìn)展，2002，29: 506-509

42. 范衡宇，孟小倩，霍立軍，佟超，陳大元，孫青原. Detection of spindle-associated proteins in mammalian oocytes by confocal microscopy. 生物化學(xué)與生物物理進(jìn)展, 2004, 31（1）: 54-58

43. 范衡宇，佟超，李世文，陳大元，孫青原：Microtubule organization during in vitro development of rat oocytes. 生物化學(xué)與生物物理進(jìn)展，2002, 29 (5): 708-713

44. 范衡宇，霍立軍，孫青原：Roles of calmodulin-dependent protein kinase II in meiotic maturation and fertilization of oocytes. 生物化學(xué)與生物物理進(jìn)展，2003, 30 (2) 171-174

45. 范衡宇，白玉妍，楊增明：胚泡著床窗口的分子調(diào)控。生物化學(xué)與生物物理進(jìn)展，2001, 28:11-16

46. Li MY,Fan HY, Tong C, Chen DY, Xia GL, Sun QY. Mitogen-activated protein kinase regulates cell cycle progression in pig oocytes and fertilized eggs., 2002, 47: 843-847

47. 霍立軍，范衡宇，陳大元，孫青原. 卵母細(xì)胞減數(shù)分裂和受精過程中MAPK和MPF的作用和相互調(diào)節(jié). 自然科學(xué)進(jìn)展, 2004,14: 256-261

48. 白玉妍，范衡宇，楊增明：同源盒基因與哺乳動(dòng)物生殖。 生物化學(xué)與生物物理進(jìn)展，2001, 28: 329-332

49. 范衡宇，佟超， 李世文，陳大元，孫青原：蛋白激酶C在小鼠卵母細(xì)胞成熟和受精中的作用。實(shí)驗(yàn)生物學(xué)報(bào)，2003, 36(1): 37-42

50. 范衡宇，楊增明：乙醇對(duì)小鼠著床前胚胎體外發(fā)育的影響。 動(dòng)物學(xué)報(bào)，2001, 47(1): 85-88

51. 范衡宇，楊增明：催產(chǎn)素及其受體與哺乳動(dòng)物的生殖。 動(dòng)物學(xué)報(bào)，2001, 47(4):453-458

52. 范衡宇，佟超，孫青原：絲裂原活化蛋白激酶（MAPK）信號(hào)通路的研究進(jìn)展。動(dòng)物學(xué)雜志, 2002, 37: 98-102

53. 范衡宇，佟超，孫青原：絲裂原活化蛋白激酶（MAPK）信號(hào)通路與受精。 生命的化學(xué)，2001，21(4): 308~310

54. 范衡宇：與“implantation”相關(guān)的幾個(gè)概念的討論。 細(xì)胞生物學(xué)雜志，2001, 23: 230-231

55. 佟超，范衡宇，陳大元，孫青原：Parthenogenetic activation of mouse eggs induced by cycloheximide is calcium-dependent and can be blocked by okadaic acid. 動(dòng)物學(xué)報(bào), 2002, 48: 749-753

56. 佟超，范衡宇，李滿玉，陳大元，孫青原：Polo like激酶在細(xì)胞分裂中的作用研究進(jìn)展。生理科學(xué)進(jìn)展，2002，33: 45-47

57. 霍立軍，范衡宇，陳大元，孫青原：泛素-蛋白水解酶信號(hào)通路在卵母細(xì)胞減數(shù)分裂和受精中的作用。細(xì)胞生物學(xué)雜志， 2003, 25(2):73-77

58. 范衡宇，楊增明：前列腺素及其受體與哺乳動(dòng)物的生殖。生理科學(xué)進(jìn)展，2000, 31(1): 75-78