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、刘芳铭助理研究员，浦洋副研究员、张宏冰教授

课题组成员发表的代表性论文:

1.     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 Feb 18:S0012-3692(23)00272-6. doi: 10.1016/j.chest.2023.02.026.

2.     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.

3.     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.

4.     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.

5.     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.

6.     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. doi: 10.1002/ame2.12266.

7.     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.

8.     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.

9.     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.

10.   Cheng C, Wang Y, Hu D, Zhou W, Liu C, Tian X, Zhang H, Xu YC, Xu KF. Humoral response to inactivated SARS-CoV-2 vaccines in patients on sirolimus alone. Sci China Life Sci. 2022 Apr 21:1-3. doi: 10.1007/s11427-022-2102-3.

11.   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.

12.   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.

13.   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.

14.   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.

15.   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.

16.   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.

17.   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.

18.   Wang Y, Wan YY. Golgi protein 73, hepatocellular carcinoma and other types of cancers. Liver Res. 2020 Dec;4(4):161-167.

19.   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.

20.   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.

21.   Wang Y, Zhang H. Regulation of Autophagy by mTOR Signaling Pathway. Adv Exp Med Biol. 2019;1206:67-83.

22.   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.

23.   吴玉婷，马茜，汤步富，刘芳铭，靳迪，王玲，盖晓晨，张宏冰。氯化锂对第10号染色体缺失的磷酸酶及张力蛋白同源基因缺失肿瘤的疗效分析 [J].中华医学杂志, 2019,99( 30 ): 2362-2366.

24. 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识(2018)。中华结核和呼吸杂志,2019,42( 2 ): 92-97。

25. 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，中华医学杂志 2018;98(2):154-155。

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.   Liu KM, Zhang HH, Wang YN, Wang LM, Chen HY, Long CF, Zhang LF, Zhang HB, Yan HB. Wild-type p53-induced Phosphatase 1 Deficiency Exacerbates Myocardial Infarction-induced Ischemic Injury. Chin Med J (Engl). 2017;130(11):1333-1341.

30.   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.

31.   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.

32.   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

33.   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.

34.   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.

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;149:741–752.

36.   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

37.   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.

38.   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

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; 289:29739-49 (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; 33:4352-8.

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: 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.   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 

45.   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

46.   Peng H, Liu J, Sun Q, Chen R, Wang Y, Duan J, Li C, Li B, 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

47.   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

48.   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.

49.   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.

50.   Sun Q, Chen X, Ma J, Peng H, Wang F, Zha X, Wang Y, Jing Y, Yang H, Chen R, Chang L, Zhang Y, 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.

51.   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.

52.   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.

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

54.   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.

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

56.   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.

57.   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.

58.   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.

59.   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.

60.   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.

61.   Lee L, Sudentas P, Donohue B, Asrican K, Worku A, Walker V, Sun Y, Schmidt K, Albert MS, El-Hashemite N, Lader AS, Onda H, 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.

62.   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.

63.   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.

64.   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.

65.   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.

66.   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.

67.   Onda H, Crino P, Zhang H, Murphey R, Rastelli L, Rothberg BG, Kwiatkowski DJ. Tsc2 null murine neuroepithelial cells are a model for human tuber giant cells, and show activation of an mTOR pathway. Mol Cell Neurosci. 2002, 21: 561-74.

68.   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.

69.   Zhang HB, Tombline G, Weber BL. BRCA1, BRCA2, and DNA Damage Response: Collision or Collusion? Cell. 1998, 92, 433-6.

70.   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.

71.   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.

72.   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.

73.   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.

74.   Muschel RJ, Zhang HB, Iliakis G, McKenna WG. Effects of ionizing radiation on cyclin expression in HeLa cells. Radiation Res. 1992, 132:153-7.

75.   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.

76. 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

国家自然科学基金杰出青年基金、重点项目、面上项目，科技部国家重点基础研究发展计划、国家科技重大专项、国家863计划重大项目，中国教育部博士生基金，中国医学科学院医学与健康科技创新工程，美国中华医学基金会杰出教授基金。

发现结节性硬化症（TSC）肿瘤抑制基因TSC1和TSC2的蛋白复合体抑制mTOR，TSC1或TSC2基因突变导致mTOR活化引起TSC，mTOR抑制剂为其靶向治疗药物（现已成为全球一线靶向治疗）；mTOR通过激活糖酵解酶促进细胞发生有氧糖酵解（Warburg 效应），促进肿瘤发生发展；过度活化的mTOR通过增加脱黑色素的产生并抑制了真黑素合成从而抑制铁死亡、促进细胞增殖和肿瘤形成；功能亢进的mTOR反馈性抑制上游信号通路是良性肿瘤发生的一个机制；mTOR通过Notch级联反应调节细胞分化，过度活化的mTOR上调Notch抑制分化是恶性肿瘤低分化机制；GOLM1（GP73）通过平衡Notch信号维持肠上皮（IEC）稳态，GOLM1的耗竭异常激活Notch，干扰IEC的分化成熟，促进炎性结肠癌的发生；mTOR上调GP73促进肝癌的发生发展，阻断GP73可治疗肝癌；mTOR功能亢进促进垂体瘤发展, mTOR-PTTG1信号通路是垂体瘤治疗靶点；雷帕霉素有效治疗血管增生性消化道出血；激活自噬、抑制CREB1进而减少DNA损伤和细胞凋亡是雷帕霉素引起化疗抵抗的机制； RNF43的缺失与KRAS过度活化促进胰腺囊肿恶性转化，Wnt抑制剂是这类胰腺癌靶向药物；β-catenin活化突变通过刺激嘧啶合成、上调铁代谢促进肝癌发生发展；禽流感病毒H5N1通过抑制mTOR通路而引起自噬性细胞死亡，提出抑制自噬可治疗禽流感；随着新冠病毒在人群不断传播，其毒力降低，但传染性增强。