劉明耀

1993年到1998年先後在美國約翰-霍普金斯大學醫學院神經科學系和加州理工學院生物學部做博士后研究；1999至2007年先後在美國德克薩斯農工大學生物科學與技術研究所任助理教授、副教授及終身教授。

2007年受聘回國加入華東師範大學，組建生命醫學研究所並任所長；2011年12月起擔任上海市調控生物學重點實驗室主任，同年起擔任教育部創新團隊帶頭人、國家重大科學研究計劃（973項目）首席科學家；2012年入選上海市優秀學科帶頭人，2012年起任華東師範大學生命科學學院院長。

研究領域

劉明耀教授致力於G蛋白偶聯受體（GPCR）在個體發育和腫瘤及重大疾病發生髮展過程中的功能及信號轉導機理研究，以及靶向GPCR的新葯研發。

G-蛋白偶聯受體及其信號轉導途徑基因敲除和轉基因動物。

細胞信號網路與疾病。

血管新生與分子藥理學。

幹細胞和發育生物學。

生殖和代謝疾病。

腫瘤生長與轉移的分子機理。

劉明耀教授的研究領域主要涉及發育和疾病過程中G-蛋白偶聯受體(GPCRs)及其信號轉導途徑在胚胎髮育和疾病發生過程中的作用（包括生殖系統、癌症、糖尿病、骨骼和心血管系統）。G-蛋白偶聯受體是已知數目最多的細胞表面受體家族，它們把多種多樣的胞外信號傳遞到細胞內，並通過和其它信號轉導途徑間的相互作用廣泛參與細胞增殖、分化、遷移，尤其是各類生理活動和疾病的調控。劉明耀教授實驗室研究的總體目標就是利用基因敲除和轉基因動物技術平台研究構建疾病模型並研究GPCRs在生物體中的功能；利用細胞信號轉導網路技術平台來闡明GPCRs在正常和疾病狀態下的細胞和分子機制。其最終目標是開發特異靶向性膜受體和信號途徑的疾病治療藥物。研究領域集中在G蛋白偶聯受體(GPCRs)及其信號轉導途徑，包括1）發育和代謝疾病；2）腫瘤發生，發展和轉移的分子機理；3）血管新生和抗血管新生藥物的分子機制及新葯研發；4）炎症和腫瘤免疫中G蛋白偶聯受體介導的NF-КB信號途徑；5）幹細胞分化調控和人類疾病轉基因動物模型的建立。

課題

回國後作為首席科學家主持中國重大科學研究計劃1項，主持國家自然科學基金重點項目2項，參與國家重大專項新葯創製項目1項。

主持多項美國國立衛生研究院（NIH）研究項目。

主持多項美國國防部（DOD）研究項目。

主持中國科委973前期項目一項。

主持上海市科委"細胞信號轉導網路研究技術"研發公共服務平台。

論文

已在Science、Nature、Nature Biotechnology、PNAS、J Natl Cancer Inst等國際學術刊物上發表SCI論文150多篇。

1) Liu, M., Chen, T.-Y., Ahamed, B., Li, J. and Yau, K.-Y. (1994) Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. Science 266, 1348-1354. (Research Article)

2) Liu, M. and Simon, M.I. (1996) Regulation by cAMP-dependent protein kinase of a G-protein mediated phospholipase C. Nature 38, 82-87 (1996).

3) Xia, C., Bao, Z., Tabassum, F., Qiu, M., Hua, S.-B., and Liu, M. (2000) GCIP, a novel human Grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity. J. Biol. Chem. 275, 20942-20948.

4) Yue, C., Ku, CY, Liu, M., Simon, M.I., and Sanborn, B.M. (2000) Molecular mechanism of the inhibition of phospholipase C-b3 by protein kinase C. J. Biol. Chem. 275, 30220-30225.

5) Ma, W., Xia, C., Ling, P., Qiu, M., Tan, T.-H., and Liu, M. (2001) Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor kinase 1 (HPK1) to activate the JNK signaling pathway in T cells. Oncogene 20, 1703-1714.

6) Xia, C., Bao, Z., Yu, C., Sanborn, B., and Liu, M. (2001) Regulation of G-protein mediated phospholipase C-b by cGMP-dependent protein kinase. J. Biol. Chem. 276, 19770-19777.

7) Kim, H.W., Yang, P., Qyang, Y., Lai, H., Du, H., Henkel, J.S., Kumar, K., Bao, S., Liu, M., and Marcus, S. (2001) Genetic and molecular characterization of Skb15, a highly conserved inhibitor of the fission yeast PAK, ShK1. Molecular Cell, 7, 1095-1101.

8) Xia, C., Ma, W., Stafford, L.J., Marcus, S., Xiong, W-C., and Liu, M. (2001) Regulation of the p21-activated kinase (PAK) by a novel human Gb-like WD-repeat protein, hPIP1. Proc. Natl. Acad. Sci. U.S.A. 98: 6174-6179.

9) Xia, C. Ma, W., Wang, F., Hua, S-B., and Liu, M. (2001) Identification of a prostate-specific G-protein coupled receptor in prostate cancer. Oncogene 20, 5903-5907.

10) Luo, Z.J., Wang, Q., Zhou, J.Z., Wang, J.B., Liu, M., He, X., Wynshaw-Boris, A., Xiong, C.X., Lu, B., Mei, L. (2002) Dishevelled Mediates AChR Clustering by Interacting with MuSK and PAK1. Neuron 35, 489-505.

11) Stafford, L.J., Xia, C., Ma, W., Cai, Y., and Liu, M. (2002) Identification and characterization of mouse metastasis-suppressor KiSS1 and its G-protein coupled receptor. Cancer Res. 62: 5399-5404.

12) Mukhopadhyay, A., Banerjee, S., Stafford, L.J., Xia, C., Liu, M., and Aggarwal, B.B. (2002) Curcumin-induced suppression of cell proliferation correlates with downregulation of the cyclin D1 expression and Cdk4-mediated retinoblastoma protein phosphorylation. Oncogene 21, 8852-8861.

13) Xiang, H., Wang, J., Mao, Y., Liu, M., Reddy, V., and Li, D.W. (2002) Human telomerase accelerates cell growth of lens epithelial cells through regulation of the genes mediating RB/E2F pathway. Oncogene 21, 3784-3791

14) Gu, J., Xia, C., Lu, W., Wu, X., and Liu, M. (2003) Regulation and phosphorylation of hematopoietic Ga15 and Ga16 by protein kinase C. J. Biol. Chem. 88, 1101-1111.

15) Guo, X., Stafford, L.J., Bryan, B., Xia, C., Ma, W., Wu, X., Liu, D., Songyang, Z., and Liu, M. (2003) A Rac/Cdc42 specific exchange factor, GEFT, mediates cell migration, proliferation and transformation. J. Biol. Chem. 278, 13207-13215.

16) Xia, C., Stafford, L.J., Ma, W., Cai, Y., Gong, L., Liu, C., Martin, J.F., and Liu, M. (2003) GGAPs, a new family of bifunctional GTP-binding and GTPase-activating proteins. Mol. Cell. Biol. 23 (7), 2476-2488.

17) Li, Z., Hannigan, M., Mo, Z., Liu, B., Lu, W., Smrcka, A., Wu, G., Liu, M., Huang, C.K., and Wu, D. (2003) A novel chemoattractant-activated Gbg and PIXa-mediated signaling mechanism for activation of Cdc42 and PAK1 that is required for direction sensing and stabilization of cell polarity. Cell 114, 215-227.

18) Weng, J., Wang, J. Cai, Y., Stafford, L.J., Mitchell, D., Ittman, M., and Liu, M. (2004) Increased expression of prostate-specific G-protein coupled receptor (PSGR) in human prostate intraepithelial neoplasia (PIN) and prostate cancers. International Journal of Cancer 113 (5):811-8.

19) Bryan, B., Kumar, V., Cai, Y., Ma, W., Wu, G., and Liu, M. (2004) GEFT, a Rho-family guanine nucleotide exchange factor, regulates neurite outgrowth and dendritic spine formation. J. Biol. Chem. 279, 45824-32. Epub 2004 Aug 17.

2005年發表的論文

20) Cai, Y., Stafford, L.J., Bryan B.A., Mitchell, D. and Liu, M. (2005) G-protein activated phospholipase C, new partners for cell polarity protein Par3 and Par6. Oncogene 24: 4293-300.

21) Bryan, B., Cai, Y., Wrighton, K., Wu, G., Feng, X.H., and Liu, M. (2005) Ubiquitination of RhoA by Smurf1 Promotes Neurite Outgrowth. FEBS Letters 579: 1015-9.

22) Provost, J.J., Olmschenk S.M., Metcalf A.L., Korpi N., Thronson H., Liu M., Wallert M.A. (2005) Phospholipase C-beta1 mediates alpha1-adrenergic receptor-stimulated activation of the sodium-hydrogen exchanger in Chinese hamster lung fibroblasts (CCL39). Biochem. Cell. Biol. 83: 123-132.

23) Bryan, B.A., Li, D., Wu, X., and Liu, M. (2005) The Rho family of small GTPases: crucial regulators of skeletal myogenesis. Cell Mol. Life Sci. 62:1547-55.

24) Bryan, B.A. and Liu, M. (2005) GEFT, an exchange factor for Rho GTPases. AfCS-Nature Molecule Pages, doi:10.1038/mp.a003469.01

25) Weng, G., Ma, W., Mitchell, D., and Liu, M. (2005) Transcriptional regulation of human prostate-specific G-protein coupled receptor (PSGR) by two distinct promoters and growth factors. J. Cell. Biochem. 96:1034-1048.

26) Bryan, B.A., Mitchell, M.C., Zhao, L., Ma, W., Stafford, L.J., Teng, B.B., and Liu, M. (2005) Modulation of muscle regeneration, myogenesis and adipogenesis by the Rho family guanine nucleotide exchange factor GEFT. Mol. Cell. Biol. 25:11089-11101.

2006年發表的論文

27) Weng J, Wang J, Hu X, Wang F, Ittmann M, Liu M. (2006) PSGR2, a novel G-protein coupled receptor, is overexpressed in human prostate cancer. Int. J. Cancer 118: 1471-1480 [Epub 2005 Oct 4].

28) Mitchell, D. C., Abdelrahim, M., Weng, J., Stafford, L.J., Safe, S., Bar-Eli, M., and Liu, M. (2006) Regulation of KiSS-1 metastasis suppressor gene expression in breast cancer. J. Biol. Chem. 281(1):51-8 [Epub 2005 Oct 27].

29) Cai, Y., Wu, P., Ozen, M., Yu, Y., Wang, J., Ittmann, M., and Liu, M. (2006) Gene expression profiling and analysis of signaling pathways of human neural stem cell priming and differentiation. Neuroscience 138(1):133-48 [Epub 2006 Jan 18].

30) Bryan, B.A., Cai, Y., and Liu, M. (2006) Rho family guanine nucleotide exchange factor GEFT enhances retinoic acid- and cAMP-induced neurite outgrowth. J. Neuroscience Res. 83 (7):1151-9.

31) Wang, J., Weng, J., Cai, Y., Penland, R., Liu, M., and Ittmann, M. (2006) The prostate specific G-protein coupled receptors PSGR and PSGR2 are prostate cancer biomarkers that are complementary to b-methylacyl-CoA racemase. The Prostate 66 (8):847-57.

32) Ma, W., Xia, X., Stafford, L.J., Yu, C., Wang, F., LeSage, G., and Liu, M. (2006) Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis. Oncogene 25, 4207-16 [Epub 2006 Feb 27].

2007年發表的論文

33) Hsu, Y-C., Chern, J.J., Cai, Y., Liu, M., and Choi, K.W. (2007) Drosophila Homolog of TCTP Regulates Cell Growth and Proliferation through regulation of dRheb GTPase. Nature 445 (7129), 785-788.

34徠) Li, D., Mitchell, D.C., Luo, J., Yi, Z., Cho, S.-G., Li, X., Ning, G., Wu, X., and Liu, M. (2007) Estrogen regulates KiSS1 gene expression through estrogen receptor a and SP protein complexes. Endocrinology 2007 Jul 26; [Epub ahead of print] PMID: 17656465

35) Mitchell, D.C., Bryan, B.A., Liu, J.P., Liu, W.B., Zhou, X., Qu, J., Hurwitz, R., Liu, M., and Li, D.W. (2007) Differential Expression of Rho family of GTPases during mouse eye development. Molecular Vision 13:1144-53.

36) Kunnumakkara, A.B., Nair, A.S., Ahn, K.S., Pandey, M.K., Yi, Z.F., Liu, M., and Aggarwal, B.B. (2007) Gossypin, a pentahydroxy glucosyl flavone, inhibits the transforming growth factor beta-activated kinase-1 mediated NF-kB activation pathway, leading to potentiation of apoptosis, suppression of invasion, and abrogation of osteoclastogenesis. Blood 109 (12):5112-21. Epub 2007 Mar 1

37) Shi, H.Y., Stafford, L.J., Liu, Z., Liu, M., and Zhang, M. (2007) Maspin controls mammary tumor cell migration through inhibiting Rac1 and Cdc42, but not RhoA GTPase. Cell Motility and Cytoskeleton 64 (5):338-46. [Epub 2007 Feb 14].

38) Wrighton, K.H., Liang, M., Bryan, B.A., Luo, K., Liu, M., Feng, X.H., and Lin, X. (2007) TGF-beta-independent regulation of myogenesis by SnoN sumoylation. J. Biol. Chem. 282(9):6517-24. [Epub ahead of print] PMID: 17202138

39) Ma, W., Stafford, J.L., Li, D., Luo, J., Li, X., Ning, G., and Liu, M. (2007) GCIP/ CCNDBP1, a helix-loop-helix leucine-zip protein, suppresses tumorigenesis. Journal of Cell. Biochem 100 (6):1376-86.

40) Mitchell, D.C., Stafford, L.J., Li, D., Bar-Eli, M., and Liu, M. (2007) Transcriptional Regulation of KiSS-1 Gene Expression in Metastatic Melanoma by Specificity Protein-1 and its Coactivator DRIP-130. Oncogene 26 (12):1739-47.

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