张宏冰



课题组成员：硕士生5名、博士生5名、博士后1名、邓唯唯主管技师、王亚南、浦洋、邓敬娜助理研究员、张宏冰教授
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。

课题组成员发表的代表性论文:
1. Li C, Chen H, Lan Z, He S, Chen R, Wang F, Liu Z, Li K, Cheng L, Liu Y, Sun K, Wan X, Chen X, Peng H, Li L, Zhang Y, Jing Y, Huang M, Wang Y, Wang Y, Jiang J, Zha X, Chen L, Zhang H. mTOR-dependent upregulation of xCT blocks melanin synthesis and promotes tumorigenesis. Cell Death Differ. 2019 Feb 13. doi: 10.1038/s41418-019-0274-0. [Epub ahead of print]

2. 中华医学会呼吸病学分会间质性肺疾病学组, 淋巴管肌瘤病共识专家组, 中国医学科学院罕见病研究中心等. 西罗莫司治疗淋巴管肌瘤病专家共识（2018）. 中华结核和呼吸杂志,2019,42( 2 ): 92-97.

3. Hu D, Mao Y, Xu G, Liao W, Ren J, Yang H, Yang J, Sun L, Chen H, Wang W, Wang Y, Sang X, Lu X, Zhang H, Zhong S. Time-restricted feeding causes irreversible metabolic disorders and gut microbiota shift in pediatric mice. Pediatr Res. 2019;85(4):518-526.
4.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. 2018;25(6):1160-1173.
5.Xu KF, Tian X, Yang Y, ZhangH. Rapamycin for Lymphangioleiomyomatosis: Optimal time and optimal dosage.Thorax 2018;73(4):308-310.
6.王冬梅，孟真，张宏冰。雷帕霉素靶蛋白抑制剂西罗莫司治疗晚期骨髓纤维化二例，中华医学杂志 2018;98(2):154-155。
7.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
8.Xu MM, Pu Y, Han D, Shi Y,Cao X, Liang H, Chen X, Li XD, Deng L, Chen ZJ, Weichselbaum RR, Fu YX.Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA forCross-priming through Signal Regulatory Protein α Signaling. Immunity.2017;47(2):363-373.e5.
9.Xu MM, Pu Y, WeichselbaumRR, Fu YX. Integrating conventional and antibody-based targeted anticancertreatment into immunotherapy. Oncogene. 2017 Feb 2;36(5):585-592.
10.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 andclinical characteristics of a Chinese Kallmann syndrome cohort with ANOS1mutations. Eur J Endocrinol. 2017:177(4):389-398.
11.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-complexsuppression of SOX9-osteopontin-AKT signalling cascade constrains tumour growthin tuberous sclerosis complex. Hum Mol Genet. 2017;26(2):407-419
12.Liu KM, Zhang HH, Wang YN, Wang LM, Chen HY,Long CF, Zhang LF, Zhang HB, Yan HB. Wild-type p53-induced Phosphatase 1Deficiency Exacerbates Myocardial Infarction-induced Ischemic Injury. Chin MedJ (Engl). 2017;130(11):1333-1341.
13.Wu H, Wu Z, Li P, Cong Q, ChenR, 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 ofmTOR in Mesenchymal Stromal Cells and Osteoclasts. Stem Cell Reports. 2017:8(6):1600-1616.
14.Pu Y, Xu M, Liang Y, Yang K,Guo Y, Yang X, Fu YX. Androgen receptor response against prostate cancerleading to early tumor relapse. Sci. Transl. Med. 2016 Apr 6;8(333):333ra47
15.Liu Z, MaoJ, Wu X, Xu H, Wang X, Huang B, Zheng J, Nie M, Zhang H. Efficacy and OutcomePredictors of Gonadotropin Treatment for Male Congenital HypogonadotropicHypogonadism. Medicine 2016;95(9):e2867.
16.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 ofglycolytic genes by regulating KPNA2 abundances. J Proteomics. 2016;136:13-24.
17. Chen X,Wang Y, Tao J, Shi Y, Gai X, Huang F, Ma Q, Zhou Z, Chen H, Zhang H, Liu Z, SunQ, Peng H, Chen R, Jing Y, Yang H, Mao Y, Zhang H. mTORC1 Upregulates GP73 toPromote Proliferation and Migration of Hepatocellular Carcinoma Cells andGrowth of Xenograft Tumors in Mice. Gastroenterology. 2015;149(3):741–752.
18.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-mediatedTumorigenesis. J Biol Chem.2015; 290 (42):25756-65.
19.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 wholegenome sequencing for complex congenital disorder. J Genet Genomics. 2015; 42(11):651-5
20.Jin D, Tao J, Li D, Wang Y, LiL, Hu ZD, Zhou ZZ, Chang XL, Qu CF, Zhang H. Golgi protein 73 activation ofMMP-13 promotes hepatocellular carcinoma cell invasion Oncotarget. 2015; 6(32):33523-33.
21.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;95:3424-7.
21.Zha X, Hu Z, Ji S, Jin F, Jiang K, Li C, ZhaoP, Tu Z, Chen X, Di L, Zhou H, Zhang H. NFκB up-regulation of glucosetransporter 3 is essential for hyperactive mammalian target ofrapamycin-induced aerobic glycolysis and tumor growth. Cancer Lett. 2015; 359:97-106
23.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 ofWild-type p53-induced phosphatase 1 promotesliver regenerationinmice by direct activation ofmTOR. Hepatology. 2015; 61:2030-41
24.Mao JF, Xu HL, Duan J, Chen RR, Li L, Li B,Nie M, Min L, Zhang HB, Wu XY. Reversal of idiopathic hypogonadotropichypogonadism: a cohort study in Chinese patients. Asian J Androl. 2015;17:497-502.
25.Liu Z, Chen X, Wang Y, Peng H, Wang Y, JingY, Zhang H. PDK4 Protein Promotes Tumorigenesis through Activation ofcAMP-response Element-binding Protein (CREB)-Ras Homolog Enriched in Brain(RHEB)-mTORC1 Signaling Cascade. J Biol Chem. 2014; 289 (43):29739-49 (Paper ofthe Week).
26.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 bydeficient TSC1/2 complex. Oncogene. 2014; 33(34):4352-8.
27.Liu Z, XuKF, Hu C, Chen R, Duan J, Shi Y, Wang Y, Zhang W, Moss J,Wu J,ZhangH. Use of whole-exome sequencing for the diagnosis ofatypicalBirt-Hogg-Dubé syndrome. J Genet Genomics. 2014; 41(8): 449-151
28.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 mTORhyperactivation in vascular endothelial cells causes angiogenesis defects andembryonic lethality. Hum Mol Genet. 2014; 23: 693-705
29.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
30.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. NatureCommun. 2014; 5:4696.
31.Wang W,Liu J, Ma A, Miao R, Jin Y, Zhang H, Xu K, Wang C, Wang J. mTORC1 is involvedin hypoxia-induced pulmonary hypertension through the activation of Notch3. JCell Physiol. 2014; 229: 2117-25
32.Wang Y, HuZ, Liu Z, Chen R, Peng H, Guo J, Chen X, Zhang H. MTOR inhibitionattenuates DNA damage and apoptosis through autophagy-mediated suppression ofCREB1. Autophagy. 2013;9(12):2069-86.
33.Peng H,Liu J, Sun Q, Chen R, Wang Y, Duan J, Li C, Bin Li, Jing Y, Chen X, Mao Q, XuKF, Walker CL, Li J, Wang J, Zhang H. mTORC1 enhancement of STIM1-mediatedstore-operated Ca2+ entry constrains tuberous sclerosis complex-related tumordevelopment. Oncogene. 2013; 32(39):4702-11.
34.LiH,Wang J,Xu H,Xing R,Pan Y,Li W,CuiJ,ZhangH, Lu Y. Decreased fructose-1,6-bisphosphatase-2expressionpromotesglycolysisandgrowthingastriccancercells.MolCancer. 2013; 12(1):110
35.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 cytotoxicityin pituitary adenoma cell lines in vitro and xenografted pituitary adenoma infemale nude mice. Endocrinology. 2013; 154: 1247-1259.
36. He J, KangL, Wu T, Zhang J, Wang H, Gao H, Zhang Y, Huang B, Liu W, Kou Z, Zhang H, GaoS. An elaborate regulation of mTOR activity is required for somatic cellreprogramming induced by defined transcription factors. Stem Cells Dev. 2012; 21: 2630-41.
37. Zhang Y,Du XL, Wang CJ, Lin DC, Ruan X, Feng YB, Huo YQ, Peng H, Cui JL, Zhang TT, WangYQ, Zhang H, Zhan QM, Wang MR. Reciprocal activation between PLK1 and Stat3contributes to survival and proliferation of esophageal cancer cells. Gastroenterology.2012; 142: 521-30.
38. 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 na?ve CD8 T cell survivaland homeostasis in mice. PLoS One. 2012; 7: e30592.
39.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, ZhangH. Mammalian target of rapamycin upregulation of pyruvate kinase isoenzyme typeM2 is critical for aerobic glycolysis and tumor growth. Proc Natl Acad Sci USA2011, 108: 4129-34.
40.Ma J, Sun Q, Mi R, Zhang H. Avian influenza Avirus H5N1 causes autophagy-mediated cell death through suppression of mTORsignaling. J Genet Genomics. 2011, 38: 533-7.
41.Zha X, Hu Z, He S, Wang F, Shen H, Zhang H.TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation ofSTAT3-PTEN cascade. Cancer Lett. 2011, 313: 211-7.
42.Tian X, Shao C, Feng R, Xu K, Zhang H.Expiratory lymphatic sacs. Am J Respir Crit Care Med. 2011, 184: 1085.
43.Wu XN, Wang XK, Wu SQ, Lu J, Zheng M, WangYH, Zhou H, Zhang H, Han J. Phosphorylation of raptor by p38β participates inarsenite-induced mammalian target of rapamycin complex 1 (mTORC1) activation. J Biol Chem. 2011,286:31501-11.
44.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 GP73expression in hepatocellular carcinoma tissue correlates with tumor aggressionbut not survival. J Gastroenterol Hepatol. 2011, 26:1207-12.
45.Zha X, SunQ, Zhang H. mTOR upregulation of glycolytic enzymes promotes tumor development.Cell Cycle 2011, 10: 1015-6
46.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 forenergy-depletion-induced suppression of mTORC1. Nature Cell Biol. 2011, 13;263-72
47.Zha X,Wang F, Wang Y, He S, Jing Y, Wu X, Zhang H. Lactate dehydrogenase B iscritical for hyperactive mTOR-mediated tumorigenesis. Cancer Res. 2011, 71;13–8.
48.Mao Y, Yang H, Xu H, Lu X, Sang X, Du S, ZhaoH, 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 avaluable serum marker for hepatocellular carcinoma. Gut. 2010, 59:1687-93.
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 ofMdm2 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 andhuman cell differentiation through STAT3/p63/Jagged/Notch cascade. J ClinInvest. 2010, 120: 103-14.
51.Mi R, Ma J, Zhang D, Li L, Zhang H. Efficacy ofcombined inhibition of mTOR and ERK/MAPK pathways in treating a tuberoussclerosis 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.Zhang J., B. Wang, Z. Xiao, Y. Zhao, B. Chen,J. Han, Y. Gao, W. Ding，Zhang H, J. Dai. Olfactory ensheathingcells promote proliferation and inhibit neuronal differentiation of neuralprogenitor cells through activation of Notch1. Neuroscience 2008, 153: 406-13.
54.Zhang H, Bajraszewski N, Wu E, Wang H,Moseman AP, Dabora SL, Griffin JD, Kwiatkowski DJ. PDGF receptors are criticalfor PI3K/AKT activation and negatively regulated by mTOR. J Clin Invest. 2007,117: 730-8.
55.Lee L, Sudentas P, Donohue B, Asrican K,Worku A, Walker V, Sun Y, Schmidt K, Albert MS, El-Hashemite N, Lader AS, OndaH, Zhang H, Kwiatkowski DJ, Dabora SL. Efficacy of a rapamycin analog (CCI-779)and IFN-gamma in tuberous sclerosis mouse models. Genes Chromosomes Cancer.2005, 42: 213-27.
56.Chan JA, Zhang H, Roberts PS, Jozwiak S,Wieslawa G, Lewin-Kowalik J, Kotulska K, Kwiatkowski DJ. Pathogenesis oftuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivationof TSC1 or TSC2 leads to mTOR activation. J Neuropath Exp Neur. 2004,63:1236-42.
57.El-Hashemite N, Zhang H, Walker V,Hoffmeister KM, Kwiatkowski DJ. Perturbed IFNg-Jak-stat signaling in tuberousesclerosis mouse models: synergistic effects of rapamycin-IFNg treatment. CancerRes. 2004, 64: 3436-43.
58.Finlay GA, York B, Karas RH, Fanburg BL,Zhang H, Kwiatkowski DJ, Noonan DJ. Estrogen-induced smooth muscle cell growthis regulated by tuberin and associated with altered activation ofplatelet-derived growth factor receptor-beta and ERK-1/2. J Biol Chem 2004,279: 23114-22
59.Zhang H, Cicchetti G, Onda H, Koon HB,Asrikan K, Bajraszewski N, Vazquez P. Carpenter C, Kwiatkowski DJ. Loss ofTsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signalling throughdownregulation of PDGFR. J Clin Invest. 2003, 112: 1223-33.
60.El-Hashemite N, Walker V, Zhang H,Kwiatkowski DJ. Loss of tuberous sclerosis complex genes induces vascularendothelial growth factor production through mTOR pathway. Cancer Res. 2003,63: 5173-7.
61.El-Hashemite N, Zhang H, Henske EP,Kwiatkowski DJ. Mutation in TSC2 and activation of mammalian target ofrapamycin signalling pathway in renal angiomyolipoma. Lancet. 2003, 361:1348-9.
62.Onda H, Crino P, Zhang H, Murphey R, RastelliL, Rothberg BG, Kwiatkowski DJ. Tsc2 null murine neuroepithelial cells are amodel for human tuber giant cells, and show activation of an mTOR pathway. MolCell Neurosci. 2002, 21: 561-74.
63.Kwiatkowski DJ, Zhang H, Bandura JL,Heiberger KM, Onda H. A mouse model of TSC1 reveals sex-dependent lethalityfrom liver hemangiomas, and up-regulation of p70S6 kinase activity in TSC1 nullcells. Hum Mol Genet. 2002, 11: 525-34.
64.Houvras Y, Benezra M, Zhang H, Manfredi JJ,Weber BL., Licht JD. BRCA1 physically and functionally interacts with the ATF1transcription factor. J Biol Chem. 2000, 275: 36230-7.
65.Sun J, Paddock C, Shubert J, Zhang H, Amin K,Newman PJ, Albelda SM. Contributions of the extracellular and cytoplasmic domainsof platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) in regulatingcell-cell localization. J Cell Sci. 2000, 113:1459-69.
66.Liu L, Scolnick DM, Trievel RC, Zhang HB,Marmorstein R, Halazonetis TD, Berger SL. p53 sites acetylated in vitro by PCAFand p300 are acetylated in vivo in response to DNA damage. Mol Cell Biol. 1999,19:1202-9.
67.Zhang HB, TomblineG, Weber BL. BRCA1, BRCA2, and DNA Damage Response: Collision or Collusion? Cell. 1998, 92, 433-6.
68.Zhang H, Somasundaram K, PengY, Tian H, Zhang H, Bi D, Weber BL, El-Deiry WS. BRCA1 physically associateswith p53 and stimulates its transcriptional activity. Oncogene. 1998, 16: 1713-21.
69.Somasundaram K, Zhang HB (equalcontribution as the first author), Zeng YX, Houvras Y, Peng Y, Zhang H, Wu GS,Licht JD, Weber BL, El-Deiry WS. Arrest of the cell cycle by thetumour-suppressor BRCA1 requires the CDK-inhibitor p21^WAF1/CiP1. Nature. 1997, 389: 187-90.
70.Thakur S, ZhangHB, Peng Y, Le H, Carroll B, Ward T, Yao J, Farid LM, Couch F, WilsonRB, Weber BL. Localization of BRCA1 and a splice variant identifies the nuclearlocalization signal. Mol Cell Bio.1997, 17: 444-52.
71.Elshami AA, Saavedra A, Zhang H, Kucharczuk JC, Spray DC,Fishman GI, Amin KM, Kaiser LR, Albelda SM. Gap-junctions play a role in thebystander effect of the herpes-simplex virus thymidine kinase ganciclovirsystem in-vitro. Gene Therapy.1996, 85-92.
72.Elshami AA, Kucharczuk JC, Zhang HB, Smythe WR, Hwang HC,Litzky LA, Kaiser LR, Albelda SM. Treatment of pleural mesothelioma in animmunocompetent rat model utilizing adenoviral transfer of the herpes-simplexvirus thymidine kinase gene. Human Gene Therapy. 1996, 141-8.
73.Kucharczuk JC, Elshami AA, Zhang HB, Smythe WR, Hwang HC,Tomlinson JS, Amin KM, Litzky LA, Albelda SM, Kaiser LR. Pleural basedmesothelioma in immune competent rats--a model to study adenoviralgene-transfer. Ann Thoracic Surg. 1995, 60: 593-8.
74.Muschel RJ, Zhang HB, McKenna WG. Differential effect of ionizing radiation on theexpression of cyclin A and cyclin B in HeLa cells. Cancer Res. 1993, 53:1128-35.
75. Muschel RJ, Zhang HB, Iliakis G, McKenna WG. Effects of ionizing radiation oncyclin expression in HeLa cells. RadiationRes. 1992, 132:153-7.
76. Muschel RJ, ZhangHB, Iliakis G, McKenna WG. CyclinB expression in HeLa cells during the G2 block induced by ionizing radiation. Cancer Res. 1991, 51:5113-7.

77. 张宏冰、陈夏丰. 心内直视手术中心钠素与环核苷酸的研究。中华胸心血管外科杂志. 10: 234-237, 1990