课题组成员：硕士生4名，博士生4名，邓唯唯主管技师，王亚南、刘芳铭助理研究员，浦洋副研究员，张宏冰教授

负责人：张宏冰先后毕业于三峡大学医学院、华中科技大学同济医学院、美国宾夕法尼亚大学（University of Pennsylvania）医学院，曾是哈佛大学博士后、讲师。为中国医学科学院-北京协和医学院基础医学研究所长聘教授、 中华医学基金会杰出教授、国家杰出青年科学基金获得者、全球前2%顶尖科学家、2014-2022中国高被引学者。

目前研究方向：研究细胞信号传导的调节，探讨肿瘤等疾病的发生机制、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. Liu F, Wu Y, Zhang B, Yang S, Shang K, Li J, Zhang P, Deng W, Chen L, Zheng L, Gai X, Zhang H. Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis. Chin Med J (Engl). 2023 Aug 23. doi: 10.1097/CM9.0000000000002816. Epub ahead of print.
2. Chen R, Wang H, Zheng C, Zhang X, Li L, Wang S, Chen H, Duan J, Zhou X, Peng H, Guo J, Zhang A, Li F, Wang W, Zhang Y, Wang J, Wang C, Meng Y, Du X, Zhang H. Polo-like kinase 1 promotes pulmonary hypertension. Respir Res. 2023 Aug 19;24(1):204.
3. Xu W, Yang C, Cheng C, Wang Y, Hu D, Huang J, He Y, Wang J, Chen K, Yang L, Zhou W, Zhang T, Liu S, Dai J, Meng S, Li X, Yang Y, Wang ST, Feng R, Zhang W, Zhang H, Wang L, Tian X, Xu KF. Determinants of Progression and Mortality in Lymphangioleiomyomatosis. Chest. 2023 Jul;164(1):137-148. doi: 10.1016/j.chest.2023.02.026. Epub 2023 Feb 18. PMID: 36801466.
4. Wu Y, Yang S, Han L, Shang K, Zhang B, Gai X, Deng W, Liu F, Zhang H. β-catenin-IRP2-primed iron availability to mitochondrial metabolism is druggable for active β-catenin-mediated cancer. J Transl Med. 2023 Jan 26;21(1):50.
5. Tang B, Wang Y, Xu W, Zhu J, Weng Q, Chen W, Fang S, Yang Y, Qiu R, Chen M, Mao W, Xu M, Zhao Z, Cai S, Zhang H, Ji J. Macrophage xCT deficiency drives immune activation and boosts responses to immune checkpoint blockade in lung cancer. Cancer Lett. 2022 Nov 29;554:216021.
6. Wan L, Wang Y, Li J, Wang Y, Zhang H. Inhibition of the AKT/mTOR pathway negatively regulates PTEN expression via miRNAs. Acta Biochim Biophys Sin (Shanghai). 2022 Oct 25;54(11):1637-1647.
7. Liu F, Gai X, Wu Y, Zhang B, Wu X, Cheng R, Tang B, Shang K, Zhao N, Deng W, Chen J, Zhang Z, Gu S, Zheng L, Zhang H. Oncogenic β-catenin stimulation of AKT2-CAD-mediated pyrimidine synthesis is targetable vulnerability in liver cancer. Proc Natl Acad Sci U S A. 2022 Sep 27;119(39):e2202157119.
8. Gai X, Liu F, Wu Y, Zhang B, Tang B, Shang K, Wang L, Zhang H, Chen Y, Yang S, Deng W, Li P, Wang J, Zhang H. Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis. Animal Model Exp Med. 2022 Aug 16. 6(2):92-102.
9. Xie B, Pu Y, Yang F, Chen W, Yue W, Ma J, Zhang N, Jiang Y, Wu J, Lin Y, Liang X, Wang C, Zou P, Li M. Proteomic Mapping and Targeting of Mitotic Pericentriolar Material in Tumors Bearing Centrosome Amplification. Cancer Res. 2022 Jul 18;82(14):2576-2592.
10. Han L, Wu Y, Liu F, Zhang H. eIF4A1 Inhibitor Suppresses Hyperactive mTOR-associated Tumors by Inducing Necroptosis and G2/M Arrest. Int. J. Mol. Sci. 2022 Jun 22;23(13):6932.
11. Zhang X, Zheng C, Gao Z, Chen H, Li K, Wang L, Zheng Y, Li C, Zhang H, Gong M, Zhang H, Meng Y. SLC7A11/xCT Prevents Cardiac Hypertrophy by Inhibiting Ferroptosis. Cardiovasc Drugs Ther. 2022 Jun;36(3):437-447.
12. Dai Y, Zhang X, Lv J, Feng F, Wan X, Huang F, Zhang H, Zhu L. Familial uterine leiomyoma-associated germline oncogenic mutant VEGFR1 is sensitive to mTOR inhibitor. Sci Bull (Beijing). 2022 Mar 30;67(6):585-587.
13. Zhou X, Sun Z, Zhang M, Qu X, Yang S, Wang L, Jing Y, Li L, Deng W, Liu F, Di J, Chen J, Wu J, Zhang H. Deficient Rnf43 potentiates hyperactive Kras-mediated pancreatic preneoplasia initiation and malignant transformation. Animal Model Exp Med. 2022 Feb;5(1):61-71.
14. Wan LY, Peng H, Ni YR, Jiang XP, Wang JJ, Zhang YQ, Ma L, Li R, Han L, Tan Y, Li JM, Cai WL, Yuan WF, Liang JJ, Huang L, Wu X, Zhou Q, Cheng QN, Yang X, Liu MY, Ai WB, Liu CB, Zhang H, Wu JF. The miR-23b/27b/24-1 cluster inhibits hepatic fibrosis by inactivating hepatic stellate cells. Cell Mol Gastroenterol Hepatol. 2022;13(5):1393-1412.
15. Wang L, Wang F, Liu K, Long C, Chen Y, Li C, Li L, Liu F, Zhang X, Jing Y, Wang Y, Liang A, Yan H, Zhang H. αB-crystallin/HSPB2 is critical for hyperactive mTOR-induced cardiomyopathy. J Cell Physiol. 2021 Dec;236(12): 8110-8121.
16. Zhou J, Zhao Z, Sun T, Liu W, Yu Z, Liu J, Yu Y, Ning S, Zhang H. Efficacy and Safety of Sirolimus for Blue Rubber Bleb Nevus Syndrome: A Prospective Study. Am J Gastroenterol. 2021 May 1;116(5):1044-1052.
17. Pu Y, Song Y, Zhang M, Long C, Li J, Wang Y, Xu Y, Pan F, Zhao N, Zhang X, Xu Y, Cui J, Wang H, Li Y, Zhao Y, Jin D, Zhang H. GOLM1 restricts colitis and colon tumorigenesis by ensuring Notch signaling equilibrium in intestinal homeostasis. Signal Transduct Target Ther. 2021 Apr 14;6(1):148.
18. Yang H, Sun L, Pang Y, Hu D, Xu H, Mao S, Peng W, Wang Y, Xu Y, Zheng YC, Du S, Zhao H, Chi T, Lu X, Sang X, Zhong S, Wang X, Zhang H, Huang P, Sun W, Mao Y. Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure. Gut. 2021 Mar;70(3):567-574.
19. Wan X, Zhou M, Huang F, Zhao N, Chen X, Wu Y, Zhu W, Ni Z, Jin F, Wang Y, Hu Z, Chen X, Ren M, Zhang H, Zha X. AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development. Cell Death Dis. 2021 Feb 10;12(2):172.
20. Gao Y, Ma X, Bi J, Chu J, Liu B, Chi C, Yan J, Yu X, Liu F, Deng X, Zhang H, Jin B. Epidemiological and clinical differences of coronavirus disease 2019 patients with distinct viral exposure history. Virulence. 2020 Dec;11(1):1015-1023.
21. 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 Oct;26(10):2015-2028.
22. Wang Y, Zhang H. Regulation of Autophagy by mTOR Signaling Pathway. Adv Exp Med Biol. 2019;1206:67-83.
23. 徐凯峰，金美玲，刘杰，欧阳若芸，田欣伦，张波，张宏冰，中华医学会呼吸病学分会间质性肺疾病学组。西罗莫司治疗淋巴管肌瘤病专家共(2018)。中华结核和呼吸杂志,2019,42( 2 ): 92-97。
24. Gai X, Tang B, Liu F, Wu Y, Wang F, Jing Y, Huang F, Jin D, Wang L, Zhang H. miR-145-regulated exosomal GOLM1 promotes hepatocellular carcinoma through augmented GSK-3β/MMPs. J Genet Genomics. 2019 May 20;46(5):235-245.
25. 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 Mar;85(4):518-526.
26. 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.
27. Xu KF, Tian X, Yang Y, Zhang H. Rapamycin for Lymphangioleiomyomatosis: Optimal time and optimal dosage. Thorax 2018;73(4):308-310.
28. 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
29. 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 for Cross-priming through Signal Regulatory Protein α Signaling. Immunity. 2017;47(2):363-373.e5.
30. Xu MM, Pu Y, Weichselbaum RR, Fu YX. Integrating conventional and antibody-based targeted anticancer treatment into immunotherapy. Oncogene. 2017 Feb 2;36(5):585-592.
31. Pu Y, Xu M, Liang Y, Yang K, Guo Y, Yang X, Fu YX. Androgen receptor response against prostate cancer leading to early tumor relapse. Sci. Transl. Med. 2016 Apr 6;8(333):333ra47
32. 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.
33. Xu MM, Pu Y, Zhang Y, Fu YX. The Role of Adaptive Immunity in the Efficacy of Targeted Cancer Therapies. Trends Immunol. 2016 Feb;37(2):141-53.
34. Liu X, Pu Y, Cron K, Deng L, Kline J, Frazier WA, Xu H, Peng H, Fu YX, Xu MM. CD47 blockade triggers T cell–mediated destruction of immunogenic tumors, Nat Med. 2015 Oct;21(10):1209-15
35. 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(3):741–752.
36. 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 (42):25756-65.
37. 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 (11):651-5
38. 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 (32):33523-33.
39. 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
40. 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 (43):29739-49 (Paper of the Week).
41. 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(34):4352-8.
42. 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(8): 449-151
43. 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
44. 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(12):2069-86.
45. 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(39):4702-11.
46. 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
47. 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.
48. 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.
49. 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.
50. 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.
51. Tian X, Shao C, Feng R, Xu K, Zhang H. Expiratory lymphatic sacs. Am J Respir Crit Care Med. 2011, 184: 1085.
52. 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.
53. Zha X, Sun Q, Zhang H. mTOR upregulation of glycolytic enzymes promotes tumor development. Cell Cycle 2011, 10: 1015-6
54. 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.
55. 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.
56. 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.
57. 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.
58. Zhang J, Wang B, Xiao Z, Zhao Y, Chen B, Han J, Gao Y, Ding W, Zhang H, Dai J. Olfactory ensheathing cells promote proliferation and inhibit neuronal differentiation of neural progenitor cells through activation of Notch signaling. Neuroscience. 2008 May 2;153(2):406-13.
59. 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.
60. Chan JA, Zhang H, Roberts PS, Jozwiak S, Wieslawa G, Lewin-Kowalik J, Kotulska K, Kwiatkowski DJ. Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation. J Neuropath Exp Neur. 2004, 63:1236-42.
61. El-Hashemite N, Zhang H, Walker V, Hoffmeister KM, Kwiatkowski DJ. Perturbed IFNg-Jak-stat signaling in tuberouse sclerosis mouse models: synergistic effects of rapamycin-IFNg treatment. Cancer Res. 2004, 64: 3436-43.
62. Zhang H, Cicchetti G, Onda H, Koon HB, Asrikan K, Bajraszewski N, Vazquez P. Carpenter C, Kwiatkowski DJ. Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signalling through downregulation of PDGFR. J Clin Invest. 2003, 112: 1223-33.
63. El-Hashemite N, Walker V, Zhang H, Kwiatkowski DJ. Loss of tuberous sclerosis complex genes induces vascular endothelial growth factor production through mTOR pathway. Cancer Res. 2003, 63: 5173-7.
64. El-Hashemite N, Zhang H, Henske EP, Kwiatkowski DJ. Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma. Lancet. 2003, 361: 1348-9.
65. Kwiatkowski DJ, Zhang H, Bandura JL, Heiberger KM, Onda H. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in TSC1 null cells. Hum Mol Genet. 2002, 11: 525-34.
66. Zhang HB, Tombline G, Weber BL. BRCA1, BRCA2, and DNA Damage Response: Collision or Collusion? Cell. 1998, 92, 433-6.
67. Zhang H, Somasundaram K, Peng Y, Tian H, Zhang H, Bi D, Weber BL, El-Deiry WS. BRCA1 physically associates with p53 and stimulates its transcriptional activity. Oncogene. 1998, 16: 1713-21.
68. Somasundaram K, Zhang HB (equal contribution 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 the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAF1/CiP1. Nature. 1997, 389: 187-90.
69. Thakur S, Zhang HB, Peng Y, Le H, Carroll B, Ward T, Yao J, Farid LM, Couch F, Wilson RB, Weber BL. Localization of BRCA1 and a splice variant identifies the nuclear localization signal. Mol Cell Bio. 1997, 17: 444-52.
70. Muschel RJ, Zhang HB, McKenna WG. Differential effect of ionizing radiation on the expression of cyclin A and cyclin B in HeLa cells. Cancer Res. 1993, 53:1128-35.
71. Muschel RJ, Zhang HB, Iliakis G, McKenna WG. Effects of ionizing radiation on cyclin expression in HeLa cells. Radiation Res. 1992, 132:153-7.
72. Muschel RJ, Zhang HB, Iliakis G, McKenna WG. Cyclin B expression in HeLa cells during the G2 block induced by ionizing radiation. Cancer Res. 1991, 51:5113-7.