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发育疾病课题组

简介:

比较医学中心发育疾病课题组成立于2011年,课题组长为雍伟东研究员。1990 年于兰州大学获学士学位,1996年于内蒙古大学获硕士学位,1999 年在中国科学院获博士学位。2000 年至2011 年先后在美国普渡大学,印第安那大学医学院做博士后、研究助理和研究助理教授。 2011 年作为协和学者特聘教授到中国医学科学院医学实验动物研究所工作。长期从事实验动物模型的创制和发育生物学研究。首次发现激素受体共伴侣蛋白与雄性小鼠尿道下裂的关系,进一步的研究发现这与雌性激素和雄性激素受体的转录活性相关。另外通过对蛋白磷酸酶5的研究发现,癌症抑制基因p53与PP5在体内能够直接相作用,二者在蛋白和转录水平上存在相互调节关系,这对癌症抑制基因p53的研究是一个很大的推动。发表SCI 论文30 余篇。先后承担科技部863、973、重大专项课题,国家自然科学基金面等国家级项目。研究组现有研究员1名,技术员2名,研究生1名。

研究方向:

激素受体相关蛋白与发育及疾病之间的关系。利用创建的一系列与之相关的动物模型,从整体、组织、细胞、分子水平揭示这些基因在发育和疾病中的作用及其机制:

1、糖皮质激素受体(GR)相关蛋白FKBP51在肝脏糖、脂代谢及肝脏纤维化中的作用;

2、雄激素受体(AR)、雌激素受体(ER)在雄性和雌性生殖发育及行为学中的作用;

3、蛋白磷酸酶5 (PP5)与脂肪代谢,骨发育以及与肿瘤发生之间的关系。

4、利用转基因, ES细胞同源重组、CRISP/Cas9等技术创制各种细胞及大小鼠模型。

人员组成:

课题组组长:雍伟东,研究院,北京协和医院特聘教授,担任《实验动物学报》,《比较医学杂志》,“Animal Models and Experimental Medicine”编委;首届协和青年科学家联盟理事

             

组员:邓然               组员:王超

科研成果:

1.    Bin Qiu, Yuxue Xu, Lingling Zhang, Jun Wang, Ming Liu, Chao Wang, Ran Deng, Kent Williams, Robert Stewart, Zhongwen Xie, Tiebing Liang*, Weidong Yong*. Loss of FKBP5 plays a critical role in neuronal synaptic plasticity and depression-like behavior. Neuroscience. 2019 Jan 24.

2.    Spence JP, Reiter JL, Qiu B, Gu H, Garcia DK, Zhang L, Graves T, Williams KE, Bice PJ, Zou Y, Lai Z, Yong W* and Liang T*. Estrogen-Dependent Upregulation of Adcyap1r1 Expression in Nucleus Accumbens Is Associated with Genetic Predisposition of Sex-Specific QTL for Alcohol Consumption on Rat Chromosome 4. Frontiers in Genetics. 2018 Dec 04 9:513. (Co-corresponding author)

3.    Wang J, Shen T, Zhu W, Dou L, Gu H, Zhang L, Yang Z, Chen H, Zhou Q, Sánchez ER, Field LJ, Mayo LD, Xie Z, Xiao D, Lin X, Shou W*, Yong W*.  Protein phosphatase 5 and the tumor suppressor P53 down-regulate each other’s activities in mice.  J Biol Chem. 2018 Nov 23;293(47):18218-18229.

4.    Wang J, Cao Y, Qiu B, Du J, Wang T, Wang C, Deng R, Shi X, Gao K, Xie Z*, Yong W*. Ablation of protein phosphatase 5 (PP5) leads to enhanced both bone and cartilage development in mice. Cell Death Dis. 2018 Feb 12;9(2):214.

5.    Zhang L, Qiu B, Wang T, Wang J, Liu M, Xu Y, Wang C, Deng R, Williams K, Yang Z, Liang T, Yong W*. Loss of FKBP5 impedes adipocyte differentiation under both normoxia and hypoxic stress. Biochem Biophys Res Commun. 2017 Apr 15;485(4):761-767.

6.    Stechschulte LA, Qiu B, Warrier M, Hinds TD Jr, Zhang M, Gu H, Xu Y, Khuder SS, Russo L, Najjar SM, Lecka-Czernik B, Yong W*, Sanchez ER*. FKBP51 Null Mice Are Resistant to Diet-Induced Obesity and the PPARγ Agonist Rosiglitazone. Endocrinology. 2016 Oct;157(10):3888-3900 (Co-corresponding author)

7.    Gu H, Cao Y, Qiu B, Zhou Z, Deng R, Chen Z, Li R, Li X, Wei Q, Xia X, Yong W*.  Establishment and phenotypic analysis of an Mstn knockout rat. Biochem Biophys Res Commun. 2016 Aug 12;477(1):115-22.

8.    Qiu B, Luczak SE, Wall TL, Kirchhoff AM, Xu Y, Eng MY, Stewart RB, Shou W, Boehm SL, Chester JA, Yong W*, Liang T*. The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans. Int J Mol Sci. 2016 Aug 5;17(8). (Co-corresponding author)

9.    Qiu B, Bell RL, Cao Y, Zhang L, Stewart RB, Graves T, Lumeng L, Yong W*, Liang T*. Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight. J Genet Genomics. 2016 Jul 20;43(7):421-30. (Co-corresponding author)

10.    Zhang Y, Wang J, Liu J, Han J, Xiong S, Yong W, Zhao Z. Combination of ESI and MALDI mass spectrometry for qualitative, semi-quantitative and in situ analysis of gangliosides in brain. Sci Rep. 2016 May 4;6:25289.

11.    Yong W, Spence JP, Eskay R, Fitz SD, Damadzic R, Lai D, Foroud T, Carr LG, Shekhar A, Chester JA, Heilig M, Liang T. Alcohol-preferring rats show decreased corticotropin-releasing hormone-2 receptor expression and differences in HPA activation compared to alcohol-non preferring rats. Alcohol Clin Exp Res. 2014 May;38(5):1275-83.