南京大学模式动物研究所

在瑞士学习工作期间，制作和分析了癌基因蛋白激酶B（PKB/Akt）三个成员的基因敲除小鼠，并将这些突变小鼠进行交配产生了混合突变鼠和双基因敲除小鼠。对其中一些小鼠的分析发现这些小鼠存在有多器官组织发育缺陷，其中心血管发育和功能异常可能是致命的因素。我们将继续对这些PKB/Akt基因敲除小鼠进行研究，同时也开展新的研究领域。目前该实验室将对以下几个方面进行研究：

1）心血管发育和功能调控机制，主要是PKB/Akt和p38 MAPK在心血管发育和功能方面的作用。

2）PKB/Akt 促进肿瘤生长的分子机理。

发表论文：

1．Dummler B., Tschopp O., Hynx D., Yang ZZ., Dirnhofer S. & Hemmings BA.(2006) Life with a single isoform of Akt: mice lacking Akt2 and Akt3 are viable but display impaired glucose homeostasis and growth deficiencies. Mol. Cell. Biol. 26:8042-8051.

2. Zhong-zhou Yang, Oliver Tschopp, Nicolas Di-Poï, Elisabeth Bruder, Anne Baudry, Bettina Duemmler, Walter Wahli and Brian A. Hemmings. (2005) Dosage-dependent ffects of Akt1/PKBa and Akt3/PKBg on thymus, skin, cardiovascular and nervous system development in mice. Mol. Cell. Biol. 23: 10407-10418.

3．Anne Baudry, Zhong-zhou Yang and Brian A. Hemmings. (2005) PKBa is required for adipose differentiation of mouse embryonic fibroblasts. J. Cell Sci. 119:889-897.

4．Oliver Tschopp, Zhong-Zhou Yang, Daniela Brodbeck, Maja Hemmings-Mieszczak, Bettina Duemmler, Takashi Watanabe, Thomas Michaelis, Jens Frahm and Brian A. Hemmings. (2005) Essential role of protein kinase Bg (PKBg/Akt3) in postnatal brain development, but not for glucose homeostasis. Development. 132:2943-2954.

5．Nicolas Di-Poï, Chuan Young Ng, Nguan Soon Tan, Zhongzhou Yang, Brian A. Hemmings, Béatrice Desvergne, Liliane Michalik, and Walter Wahli. (2005) Epithelial-mesenchymal interactions control the activity of PPARb/d during hair follicle development. Mol. Cell. Biol. 25: 1696-1712.

6．Derek Brazil, Zhong-zhou Yang and Brian A. Hemmings. (2004) New advances in Protein Kinase B signaling: AKTion on multiple fronts. Trends Biol. Sci. 29:233-242.

7．Zhong-zhou Yang, Oliver Tschopp, Anne Baudry, Bettina Duemmler, Deborah Hynx and Brian A. Hemmings. (2004) Physiolgical functions of PKB/Akt. Biochem. Soc. Trans. 32: 350-354.

8．Jianhua Feng, Rastislav Tamaskovic, Zhong-zhou Yang, Derek Brazil, Adrian Merlo,Daniel Hess and Brian A. Hemmings.(2004) Stablization of Mdm2 via decreased ubiqutination is mediated by protein kinase B/Akt-dependent phosphorylation. J. Biol. Chem. 279:35510-35517.

9．Zhong-zhou Yang, Oliver Tschopp, Maja Hemmings-Mieszczak, Jianhua Feng, Daniela Brodbeck, Elias Perentes and Brian A. Hemmings. (2003) Protein Kinase Ba/Akt1 Regulates Placental Development and Fetal Growth. J. Biol. Chem. 278, 32124-32131.

10．Zhong-zhou Yang and Brian A. Hemmings. (2001) The complexity of protein kinase B (PKB/Akt) signaling ¾ implications for human cancer. In: Protein Modules in Cellular Signalling edited by Ludwig Heilmeyer and Peter Friedrich, pp29-40, IOS, Ohmsha.

11．Joshi Venugopal, Kazuhiko Hanashiro, Zhong-Zhou Yang and Yoshikuni Nagamine. (2005) Identification and pharmacological modulation of a caveolae-dependent signal pathway that upregulates PAI-1 in insulin-resistant adipocytes. Proc. Natl. Acad. Sci. USA. 101: 17120-17125.1.

实验室成员：

技术员 :季明

研究生：常在（博士生），栾青（硕博连读），卢双双（硕博连读），滕腾（本科生）

吕镗锋（博士生，合作培养）

国家大学生创新训练计划团队：查佶，蔡琳琳，万玲艳，朱琳

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