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张宏冰


课题组成员:硕士生5名、博士生5名、博士后1名、主管技师1名、助理研究员2名、教授1名


负责人:张宏冰是美国宾夕法尼亚大学(University of Pennsylvania)医学院博士, 哈佛大学医学院博士后、讲师。从2006年以来,任中国医学科学院-北京协和医学院生理学博士生导师,医学分子生物学国家重点实验室成员,美国中华医学基金会(CMB) 杰出教授,国家杰出青年科学基金获得者。

目前研究方向:研究细胞信号传导的调节,探讨疾病的发生机制、早期诊断和靶向治疗,为促进基础医学到临床医学的转化、疾病的精准治疗提供依据。

实验室成立以来发表的论文:

1.   Sun Q, Li S, Wang Y, Peng H, Zhang X, Zheng Y, Li C, Li L, Chen R, Chen X, Bai W, Jiang X, Liu L, Wei F, Wang B, Zhang Y, Li H, Ren X, Zhang H. Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis. Cell Death Differ. (accepted)

2.   Chen R, Duan J, Li L, Ma Q, Sun Q, Ma J, Li C, Zhou X, Chen H, Jing Y, Zhao S, Wu X, Zhang H. mTOR promotes pituitary tumor development through activation of PTTG1. Oncogene 2017;36(7):979-988

3.   Nie M, Xu H, Chen R, Mao J, Wang X, Xiong S, Zheng J, Yu B, Cui M, Ma W, Huang Q, Zhang H, Wu X. Analysis of genetic and clinical characteristics of a Chinese Kallmann syndrome cohort with ANOS1 mutations. Eur J Endocrinol. 2017:177(4):389-398.

4.   Wu H, Wu Z, Li P, Cong Q, Chen R, Xu W, Biswas S, Liu H, Xia X, Li S, Hu W, Zhang Z, Habib SL, Zhang L, Zou J, Zhang H, Zhang W, Li B. Bone Size and Quality Regulation: Concerted Actions of mTOR in Mesenchymal Stromal Cells and Osteoclasts. Stem Cell Reports. 2017: 8(6):1600-1616.

5.   Huang F, Cai P, Wang Y, Zhou X, Chen H, Liao W, Mao Y, Zha X, Zhang H, Hu Z. Up-regulation of brain-expressed X-linked 2 is critical for hepatitis B virus X protein-induced hepatocellular carcinoma development. Oncotarget 2017; 8:65789-65799

6.   Jin F, Jiang K, Ji S, Wang L, Ni Z, Huang F, Li C, Chen R, Zhang H, Hu Z, Zha X. Deficient TSC1/TSC2-complex suppression of SOX9-osteopontin-AKT signalling cascade constrains tumour growth in tuberous sclerosis complex. Hum Mol Genet. 2017;26(2):407-419

7.   Liu Z, Mao J, Wu X, Xu H, Wang X, Huang B, Zheng J, Nie M, Zhang H. Efficacy and Outcome Predictors of Gonadotropin Treatment for Male Congenital Hypogonadotropic Hypogonadism. Medicine 2016;95(9):e2867.

8.   Wang L, Zhang H, Li C, Yi Y, Liu J, Zhao Y, Tian J, Zhang Y, Wei X, Gao Y, Liang A. Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity. PLoS One 2016;11(10):e0164215.

9.   Liao W, Yang H, Xu H, Wang Y, Ge P, Ren J, Xu W, Lu X, Sang X, Zhong S, Zhang H, Mao Y. Noninvasive detection of tumor-associated mutations from circulating cell-free DNA in hepatocellular carcinoma patients by targeted deep sequencing. Oncotarget. 2016; 7(26):40481-40490. 

10.   Hu Z, Yang A, Fan H, Wang Y, Zhao Y, Zha X, Zhang H, Tu P. Huaier aqueous extract sensitizes cells to rapamycin and cisplatin through activating mTOR signaling. J Ethnopharmacol. 2016;186:143-50.

11.   Chen X, Zhu Y, Wang Z, Zhu H, Pan Q, Su S, Dong Y, Li L, Zhang H, Wu L, Lou X, Liu S. mTORC1 alters the expression of glycolytic genes by regulating KPNA2 abundances. J Proteomics. 2016;136:13-24.

12.   Chen X, Wang Y, Tao J, Shi Y, Gai X, Huang F, Ma Q, Zhou Z, Chen H, Zhang H, Liu Z, Sun Q, Peng H, Chen R, Jing Y, Yang H, Mao Y, Zhang H. mTORC1 Upregulates GP73 to Promote Proliferation and Migration of Hepatocellular Carcinoma Cells and Growth of Xenograft Tumors in Mice. Gastroenterology. 2015;149:741–752.

13.   Hu Z, Wang Y, Huang F, Chen R, Li C, Wang F, Goto J, Kwiatkowski DJ, Wdzieczak-Bakala J, Tu P, Liu J, Zha X, Zhang H. Brain Expressed X-Linked 2 Is Pivotal for Hyperactive mTOR-mediated Tumorigenesis. J Biol Chem. 2015; 290:25756-65.

14.   Chen R, Li S, Liu G, Yuan Y, Liu J, Liu T, Wu R, Sun Q, Ren X, Yi X, Zhang H. Digital karyotyping with whole genome sequencing for complex congenital disorder. J Genet Genomics. 2015; 42:651-5

15.   Jin D, Tao J, Li D, Wang Y, Li L, Hu ZD, Zhou ZZ, Chang XL, Qu CF, Zhang H. Golgi protein 73 activation of MMP-13 promotes hepatocellular carcinoma cell invasion Oncotarget. 2015; 6:33523-33.

16.   茅江峰 陈蓉蓉 伍学焱 刘兆祥 郑俊杰 王曦 聂敏 段婧 张宏冰. 先天性低促性腺激素性性腺功能减退症男性患者的性腺轴外表现和致病基因间的关系中华医学杂志, 2015,95(42) : 3424-3427.

17.   Zha X, Hu Z, Ji S, Jin F, Jiang K, Li C, Zhao P, Tu Z, Chen X, Di L, Zhou H, Zhang H. NFκB up-regulation of glucose transporter 3 is essential for hyperactive mammalian target of rapamycin-induced aerobic glycolysis and tumor growth. Cancer Lett. 2015; 359:97-106

18.   Zhang L, Liu L, He Z, Li G, Liu J, Song Z, Jin H, Rudolph KL, Yang H, Mao Y, Zhang L, Zhang H, Xiao Z, Ju Z. Inhibition of Wild-type p53-induced phosphatase 1 promotes liver regeneration in mice by direct activation of mTOR. Hepatology. 2015; 61:2030-41

19.   Mao JF, Xu HL, Duan J, Chen RR, Li L, Li B, Nie M, Min L, Zhang HB, Wu XY. Reversal of idiopathic hypogonadotropic hypogonadism: a cohort study in Chinese patients. Asian J Androl. 2015; 17:497-502.

20.   Liu Z, Chen X, Wang Y, Peng H, Wang Y, Jing Y, Zhang H. PDK4 Protein Promotes Tumorigenesis through Activation of cAMP-response Element-binding Protein (CREB)-Ras Homolog Enriched in Brain (RHEB)-mTORC1 Signaling Cascade. J Biol Chem. 2014; 289:29739-49(Paper of the Week).

21.   Wang F, Chen X, Li C, Sun Q, Chen Y, Wang Y, Peng H, Liu Z, Chen R, Liu K, Yan H, Ye BH, Kwiatkowski DJ, Zhang H. Pivotal role of augmented αB-crystallin in tumor development induced by deficient TSC1/2 complex. Oncogene. 2014; 33:4352-8.

22.   Liu Z, Xu KF, Hu C, Chen R, Duan J, Shi Y, Wang Y, Zhang W, Moss J, Wu J, Zhang H.  Use of whole-exome sequencing for the diagnosis of atypical Birt-Hogg-Dubé syndrome.  J Genet Genomics. 2014; 41: 449-151

23.   Ma A, Wang L, Gao Y, Chang Z, Peng H, Zeng N, Gui YS, Tian X, Li X, Cai B, Zhang H, Xu KF. Tsc1 deficiency-mediated mTOR hyperactivation in vascular endothelial cells causes angiogenesis defects and embryonic lethality. Hum Mol Genet. 2014; 23: 693-705

24.   Chen Y, Wang F, Li C, Wang L, Zhang H, Yan H. Acquired cardiomyopathy caused by cardiac Tsc1 deficiency. J Genet Genomics. 2014; 41: 73-7 

25.   Zhu L, Yang T, Li L, Sun L, Hou Y, Hu X, Zhang L, Tian H, Zhao Q, Peng J, Zhang H, Wang R, Yang Z, Zhang L, Zhao Y.TSC1 controls macrophage polarization to prevent inflammatory disorder. Nature Commun. 2014;5:4696.

26.   Wang F, Remke M, Bhat K, Wong ET, Zhou S, Ramaswamy V, Dubuc A, Fonkem E, Salem S, Zhang H, Hsieh TC, O'Rourke ST, Wu L, Li DW, Hawkins C, Kohane IS, Wu JM, Wu M, Taylor MD, Wu E. A microRNA-1280/JAG2 network comprises a novel biological target in high-risk medulloblastoma. Oncotarget. 2014; 6:2709-24

27.   Wang W, Liu J, Ma A, Miao R, Jin Y, Zhang H, Xu K, Wang C, Wang J. mTORC1 is involved in hypoxia-induced pulmonary hypertension through the activation of Notch3. J Cell Physiol. 2014; 229: 2117-25

28.   Wang Y, Hu Z, Liu Z, Chen R, Peng H, Guo J, Chen X, Zhang H. MTOR inhibition attenuates DNA damage and apoptosis through autophagy-mediated suppression of CREB1. Autophagy. 2013; 9: 2069-86

29.   Peng H, Liu J, Sun Q, Chen R, Wang Y, Duan J, Li C, Bin Li, Jing Y, Chen X, Mao Q, Xu KF, Walker CL, Li J, Wang J, Zhang H. mTORC1 enhancement of STIM1-mediated store-operated Ca2+ entry constrains tuberous sclerosis complex-related tumor development. Oncogene. 2013; 32: 4702-11

30.   Li H, Wang J, Xu H, Xing R, Pan Y, Li W, Cui J, Zhang H, Lu Y. Decreased fructose-1,6-bisphosphatase-2 expression promotes glycolysis and growth in gastric cancer cells. Mol Cancer. 2013; 12(1):110

31.   Chen H, Zhang L, Zhang H, Xiao Y, Shao L, Li H, Yin H, Wang R, Liu G, Corley D, Yang Z, Zhao Y. Disruption of TSC1/2 signaling complex reveals a checkpoint governing thymic CD4+CD25+Foxp3+ regulatory T-cell development in mice. FASEB J. 2013; 27: 3979-90

32.   Dai C, Zhang B, Liu X, Ma S, Yang Y, Yao Y, Feng M, Bao X, Li G, Wang J, Guo K, Ma W, Xing B, Lian W, Xiao J, Cai F, Zhang H, Wang R. Inhibition of PI3K/AKT/mTOR pathway enhances temozolomide-induced cytotoxicity in pituitary adenoma cell lines in vitro and xenografted pituitary adenoma in female nude mice. Endocrinology. 2013; 154: 1247-1259.

33.   Gui YS, Wang L, Tian X, Ma A, Cai B, Zhang H, Xu KF. SPC-Cre-ERT2 transgenic mouse used for temporal gene deletion in mouse alveolar epithelial cells. PLoS One 2012;7: e46076

34.   He J, Kang L, Wu T, Zhang J, Wang H, Gao H, Zhang Y, Huang B, Liu W, Kou Z, Zhang H, Gao S. An elaborate regulation of mTOR activity is required for somatic cell reprogramming induced by defined transcription factors. Stem Cells Dev. 2012; 21: 2630-41.

35.   Zhang Y, Du XL, Wang CJ, Lin DC, Ruan X, Feng YB, Huo YQ, Peng H, Cui JL, Zhang TT, Wang YQ, Zhang H, Zhan QM, Wang MR. Reciprocal activation between PLK1 and Stat3 contributes to survival and proliferation of esophageal cancer cells. Gastroenterology. 2012; 142: 521-30.

36.   Zhang L, Zhang H, Li L, Xiao Y, Rao E, Miao Z, Chen H, Sun L, Li H, Liu G, Zhao Y. TSC1/2 Signaling complex is essential for peripheral naïve CD8 T cell survival and homeostasis in mice. PLoS One. 2012; 7: e30592.

37.   Chen T, Yan F, Qian J, Guo M, Zhang H, Tang X, Chen F, Stoner GD, Wang X. Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus. Cancer Prev Res. 2012; 5: 41-50.

38.   Sun Q, Chen X, Ma J, Peng H, Wang F, Zha X, Wang Y, Jing Y, Yang H, Chen R, Chang L, Zhang Yu, Goto J, Onda H, Chen T, Wang MR, Lu Y, You H, Kwiatkowski DJ, Zhang H. Mammalian target of rapamycin upregulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proc Natl Acad Sci USA 2011, 108: 4129-34.

39.   Ma J, Sun Q, Mi R, Zhang H. Avian influenza A virus H5N1 causes autophagy-mediated cell death through suppression of mTOR signaling. J Genet Genomics. 2011, 38: 533-7.

40.   Zha X, Hu Z, He S, Wang F, Shen H, Zhang H. TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation of STAT3-PTEN cascade. Cancer Lett. 2011, 313: 211-7.

41.   Tian X, Shao C, Feng R, Xu K, Zhang H. Expiratory lymphatic sacs. Am J Respir Crit Care Med. 2011, 184: 1085.

42.   Wu XN, Wang XK, Wu SQ, Lu J, Zheng M, Wang YH, Zhou H, Zhang H, Han J. Phosphorylation of raptor by p38β participates in arsenite-induced mammalian target of rapamycin complex 1 (mTORC1) activation. J Biol Chem. 2011, 286:31501-11.

43.   Sun Y, Yang H, Mao Y, Xu H, Zhang J, Li G, Lu X, Sang X, Zhao H, Zhong S, Huang J, Zhang H. Increased GP73 expression in hepatocellular carcinoma tissue correlates with tumor aggression but not survival. J Gastroenterol Hepatol. 2011, 26:1207-12.

44.   Zha X, Sun Q, Zhang H. mTOR upregulation of glycolytic enzymes promotes tumor development. Cell Cycle 2011, 10: 1015-6

45.   Zheng M, Wang YH, Wu XN, Wu SQ, Lu BJ, Dong MQ, Zhang H, Sun P, Lin SC, Guan KL, Han J. Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1. Nature Cell Biol. 2011, 13; 263-72

46.   Zha X, Wang F, Wang Y, He S, Jing Y, Wu X, Zhang H. Lactate dehydrogenase B is critical for hyperactive mTOR-mediated tumorigenesis. Cancer Res. 2011, 71; 13–8.

47.   Mao Y, Yang H, Xu H, Lu X, Sang X, Du S, Zhao H, Chen W, Xu Y, Chi T, Yang Z, Cai J, Li H, Chen J, Zhong S, Mohanti SR, Lopez-Soler R, Millis JM, Huang J, Zhang H. Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut. 2010, 59:1687-93.

48.   Qin L, Wang Z, Tao L, Wang Y. ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy. Autophagy. 2010, 6:239-47.

49.   Lai KP, Leong WF, Chau JF, Jia D, Zeng L, Liu H, He L, Hao A, Zhang H, Meek D, Velagapudi C, Habib SL, Li B. S6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage response. EMBO J. 2010, 29: 2994–3006.

50.   Ma J, Meng Y, Kwiatkowsk DJ, Chen X, Peng H, Sun Q, Zha X, Wang F, Wang Y, Jing Y, Zhang S, Chen R, Wang L, Wu E, Cai G, Malinowska-Kolodziej I, Liao Q, Liu Y, Zhao Y, Sun Q, Xu K, Dai J, Han J, Wu L, Zhao RC, Shen H, Zhang H. Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade. J Clin Invest. 2010, 120: 103-14.

51.   Mi R, Ma J, Zhang D, Li L, Zhang H. Efficacy of combined inhibition of mTOR and ERK/MAPK pathways in treating a tuberous sclerosis complex cell model. J Genet Genomics. 2009, 36:355-61.

52.   Wu E, Palmer N, Tian Z, Moseman AP, Galdzicki M, Wang X, Berger B, Zhang H, Kohane IS. Comprehensive dissection of PDGF-PDGFR signaling pathways in PDGFR genetically defined cells. PLoS One. 2008, 3: e3794.  

53.   毛一雷、杨华瑜、徐海峰、桑新亭、卢欣、杨志英、张锦春、钟守先、黄洁夫、张宏冰. 新的肝癌血清标记物GP73在肝癌诊断中的初步研究。 中华医学杂志  2008, 88:948-51.

54.   Zhang J., B. Wang, Z. Xiao, Y. Zhao, B. Chen, J. Han, Y. Gao, W. Ding,Zhang H, J. Dai. Olfactory ensheathing cells promote proliferation and inhibit neuronal differentiation of neural progenitor cells through activation of Notch1. Neuroscience 2008, 153: 406-13.

55.   Zhang H, Bajraszewski N, Wu E, Wang H, Moseman AP, Dabora SL, Griffin JD, Kwiatkowski DJ. PDGF receptors are critical for PI3K/AKT activation and negatively regulated by mTOR. J Clin Invest. 2007, 117: 730-8.