张洪涛,教授、博士生导师,国家教育部新世纪优秀人才支持计划获得者,苏州大学东吴学者。现任苏州大学基础医学院副院长、医学遗传学系系主任(兼)、苏州大学癌症分子遗传学实验室主任、苏州市癌症分子遗传学重点实验室主任。
立足国内发展,10年来一直围绕非小细胞肺癌的遗传学与表观遗传学的致病机制研究开展工作。主持承担 9 项国家自然科学基金项目(8项已结题)、2项教育部人才项目(已结题)、2项江苏省自然科学基金(已结题)和1项苏州市重点实验室建设项目(已结题)和2项横向课题(在研)。以通讯作者身份在J Clin Oncol、Cancer Res、EMBO Reports、Cell Reports、Oncogene、FASEB J、Semin Cancer Biol 等国际著名期刊上发表30余篇SCI论文,他引1,000余次。2008年获江苏省科技进步奖三等奖1项(第1完成人),2014年获江苏省科学技术奖二等奖1项(第1完成人),2021年获江苏省科学技术奖三等奖1项(第1完成人),荣获2022年度江苏省行业领域(基础研究)十大科技进展(第1完成人)。现任中国抗癌协会非小细胞肺癌专业委员会常务委员、中国抗癌协会肿瘤转移专业委员会委员、Oncology Letters 和 Thoracic Cancer编委、《中国肺癌杂志》常务编委。NEJM、JAMA、Cancer Res、Oncogene、Int J Cancer、Lung Cancer等国际期刊的审稿人。
1. 肿瘤细胞与分子生物学(肺癌的TGF-β/Smads信号通路调控,蛋白翻译后修饰PTM)
2. 肿瘤表观遗传学(肺癌的非编码RNA调控机制、肺癌的RNA m6A甲基化调控机制)
一、研究内容:
课题组以研究TGF-β/Smads信号通路在肺癌发生发展、恶性转化、侵袭与转移中的作用机制为特色,密切围绕以下几个方面开展肺癌的生物学、分子遗传学与表观遗传学的调控机理研究:
1)非编码RNA(miRNA、lncRNA、circRNA)在TGF-β诱导非小细胞肺癌上皮-间质转化(EMT)中的表观调控作用机制
2)TGF-β/Smads与IL-6/JAK/STAT信号通路在非小细胞肺癌EMT过程中的协同作用机制
3)Decorin (TGF-β inhibitor)基因甲基化调控的非小细胞肺癌转移的分子机制
4)TGF-β/Smads信号通路受体基因启动子区变异与非小细胞肺癌发生发展关系
5)SOX2-TIF1γ轴向调控TGF-β诱导的EMT和NSCLC细胞的侵袭转移的机制
6)TIF1γ 泛素化TAF15调控肺腺癌细胞EMT和侵袭转移的作用机制
二、主持课题:
1. 国家自然科学基金(82273372)“TRIM33/TAF15/IL6轴调控抑制肺腺癌细胞EMT和侵袭转移的作用机制” 2023.1-2026.12;在研
2. 国家自然科学基金(82073198)“心肌素促进非小细胞肺癌侵袭转移的作用机制” 2021.1-2024.12;已结题
3. 国家自然科学基金(81872343)“Circ-PTK2/miR-429/TIF1γ轴调控TGF-β诱导的NSCLC细胞EMT的机制” 2019.1-2022.12;已结题
4. 国家自然科学基金(81672277)“lncRNA XIST/miR-367/ZEB2轴促进TGF-β诱导非小细胞肺癌EMT的表观调控机制” 2017.1-2020.12;已结题
5. 国家自然科学基金(81372277)“TGF-β/Smads与IL-6/JAK/STAT信号通路在非小细胞肺癌上皮-间质转化(EMT)过程中协同作用的机制” 2014.1-2017.12;已结题
6. 国家自然科学基金(81171894)“基于Decorin基因甲基化调控的非小细胞肺癌转移的分子机制” 2012.1-2015.12;已结题
7. 国家自然科学基金(30973425)“基于DNA甲基化的非小细胞肺癌中TGFβR3基因失活的表观遗传调控机制研究” 2010.1-2012.12;已结题
8. 国家自然科学基金(30672400)“TGFBRI基因启动子区变异与非小细胞肺癌发生发展关系的研究” 2007.1-2009.12;已结题
9. 国家自然科学基金(30400533)“非小细胞肺癌患者外周血DNA甲基化异常基因的研究及其临床意义” 2005.1-2007.12;已结题
10. 国家教育部 “新世纪优秀人才支持计划” 项目(NCET-09-0165)“非小细胞肺癌的分子遗传学和表观遗传学的致病机制研究” 2010.1-2012.12;已结题
11. 江苏省自然科学基金(BK2008162)“hOGG1基因的表观修饰与非小细胞肺癌发生发展关系的研究” 2008.6-2011.6;已结题
12. 江苏省科技厅青年科技创新人才学术带头人项目(BK2004402)“非小细胞肺癌中癌相关基因的DNA甲基化研究及其临床意义” 2005.1-2006.12;已结题
13. 教育部 “留学回国人员科研启动基金”(教外司留[2008]890号),已结题
14. 苏州市癌症分子遗传学重点实验室建设项目(SZS201209),2012.7-2015.6;已结题
讲 师:刘霞
副研究员:雷哲
博士生(16人):石浩(2025级),尹小屿(2024级),胡凌吉(2023级),王永(2022级),靳二锁(2021级),孙泽龙(2020级),王昭(2019级),苏志越(2018级),王胜洁(2017级),童新(2016级),汪龙强(2014级),李畅(2013级),杨海平(2012级)、雷哲(2011级)、刘仍允(2009级)、刘泽毅(2008级)
硕士生(48人):丁乙、许展慎(2025级),张志豪(2024级),王名宇、潘利娜(2023级),梁鹏、石浩(2022级),胡凌吉、吴高添(2021级),万立、王菲菲、尹小屿(2020级),王宇鑫、陈小燕(2019级),靳二锁、王永(2018级),孙泽龙、张伟伟 (2017级),王昭、张翠娟(2016级),苏志越、张滢溪(2015级),童新、孙天锦(2014级),万亮、杨庆慧、杨天杰(2013级),陈红兵、占雷(2012级),石祥广、徐桂丽(2011级),汪龙强、杨海平、曾园园(2010级),卢芳、宋晓雪(2009级),钱乾、孙金霞(2008级),蒋谢芳(2007级),雷哲、刘仍允、曹志飞、彭晓蓓(2006级),刘泽毅、李雯雯(2005级),尤伟明、刘霞、许林燕(2004级)
P.S.
刘泽毅,曾为美国 Kentucky 大学博士后,现为苏州大学附一院呼吸科 研究员;国家自然科学基金青年、面上项目获得者。
刘仍允,曾为美国 Johns Hopkins 大学医学院博士后,现为中山大学附一院精准医学研究院 研究员;国家自然科学基金优秀青年科学基金、面上项目获得者。
雷 哲,曾为美国 National Jewish Health 访问学者,现为苏州大学附一院病理科 副研究员;国家自然科学基金青年、面上项目获得者。
李 畅,曾为芬兰 Helsinki 大学访问学者,现为苏州大学附一院胸外科 主任医师、副教授;国家自然科学基金面上项目获得者。
汪龙强,现为美国 MD Anderson 癌症中心 博士后研究员
石祥广,现为复旦大学附属华山医院皮肤科 副研究员;国家自然科学基金优秀青年科学基金、面上项目获得者。
童 新,现为苏州大学附一院胸外科 助理研究员;国家自然科学基金青年基金项目获得者。
王胜洁,现为南京医科大学康达学院 副教授;国家自然科学基金青年基金项目获得者。
苏志越,现为苏州大学附一院病理科 博士后研究员;国家自然科学基金青年基金项目获得者。
王 昭,现为苏州大学附一院肿瘤科 助理研究员。
靳二锁,现为嘉兴大学医学院 副教授。
(1). 讲授医学本科生《医学遗传学》和卓越医师班《医学基础II》、生物技术专业的《医学遗传学》(双语)、研究生《医学分子遗传学》以及留学生的《Medical Genetics》等课程。(2). 主持承担苏州大学《医学遗传学》双语教学示范课程建设1项。(3).《Textbook of Medical Genetics》(双语教材) 编委,负责其中第10、16章节的编写。(4). 近五年来,共指导博士生6名、硕士生16名、“莙政学者”1名。
一、2023-至今发表的SCI论文(* 通讯作者)
1. Jin E, Wang S, Chen D, Wang JP, Zeng Y, Sun R*, Zhang HT*. (2024) P4HA2 activates mTOR via hydroxylation and targeting P4HA2-mTOR inhibits lung adenocarcinoma cell growth. Oncogene, 43(24):1813-1823. https://doi.org/10.1038/s41388-024-03032-1
2. Wang Z, Lei Z, Wang Y, Wang S, Wang JP, Jin E, Liu X, Sun R*, Zhang HT*. (2024) Bone-metastatic lung adenocarcinoma cells bearing CD74-ROS1 fusion interact with macrophages to promote their dissemination. Oncogene, 43(28):2215-2227. https://doi.org/10.1038/s41388-024-03072-7
二、2013-2022年间发表的SCI论文(* 通讯作者)
1. Su Z, Sun Z, Wang Z, Wang S, Wang Y, Jin E, Li C, Zhao J, Liu Z, Zhou Z, Wang Y, Chen X, Liu X, Lei Z*, Zhang HT*. (2022) TIF1γ inhibits lung adenocarcinoma EMT and metastasis by interacting with the TAF15/TBP complex. Cell Reports, 41(3):111513. (Research Article) https://doi.org/10.1016/j.celrep.2022.111513
2. Wang S, Sun Z, Lei Z*, Zhang HT*. (2022) RNA-binding proteins and cancer metastasis. Semin Cancer Biol, 86(Pt 2):748-768. (Invited Review, IF:17.012) https://doi.org/10.1016/j.semcancer.2022.03.018
3. Wang Z, Chen J, Wang S, Sun Z, Lei Z, Zhang HT*, Huang J*. (2022) RGS6 suppresses TGF-β-induced epithelial–mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4. Cell Death & Disease, 13(7):656. https://doi.org/10.1038/s41419-022-05093-0
4. Sun Z, Su Z, Zhou Z, Wang S, Wang Z, Tong X, Li C, Wang Y, Chen X, Lei Z, Zhang HT*. (2022) RNA demethylase ALKBH5 inhibits TGF-β-induced EMT by regulating TGF-β/SMAD signaling in non-small cell lung cancer. FASEB J, 36(5):e22283. (Research Article) https://doi.org/10.1096/fj.202200005RR
5. Wang S, Tong X, Li C, Jin E, Su Z, Sun Z, Zhang W, Lei Z, Zhang HT*. (2021) Quaking 5 suppresses TGF-β-induced EMT and cell invasion in lung adenocarcinoma. EMBO Reports, 22(6):e52079. (Research Article) https://doi.org/10.15252/embr.202052079
6. Tong X, Wang S, Lei Z, Li C, Zhang C, Su Z, Liu X, Zhao J, Zhang HT*. (2020) MYOCD and SMAD3/SMAD4 form a positive feedback loop and drive TGF-β-induced epithelial-mesenchymal transition in non-small cell lung cancer. Oncogene, 39(14):2890-2904. https://doi.org/10.1038/s41388-020-1189-4
7. Wang L, Tong X, Zhou Z, Wang S, Lei Z, Zhang T, Liu Z, Zeng Y, Li C, Zhao J, Su Z, Zhang C, Liu X, Xu G*, Zhang HT*. (2018) Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by controlling TIF1γ in non-small cell lung cancer. Mol Cancer, 17(1):140 (p1-18).(Research Article) https://doi.org/10.1186/s12943-018-0889-7
8. Li C, Wan L, Liu Z, Xu G, Wang S, Su Z, Zhang Y, Zhang C, Liu X, Lei Z*, Zhang HT*. (2018) Long non-coding RNA XIST promotes TGF-β-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer. Cancer Lett, 418:185-195. https://doi.org/10.1016/j.canlet.2018.01.036
9. Wang L, Yang H, Lei Z, Zhao J, Chen Y, Chen P, Li C, Zeng Y, Liu Z, Liu X, Zhang HT*. (2016) Repression of TIF1γ by SOX2 promotes TGF-β-induced epithelial-mesenchymal transition in non-small-cell lung cancer. Oncogene,35(7):867-877. https://doi.org/10.1038/onc.2015.141
10. Shi X, Zhan L, Xiao C, Lei Z, Yang H, Wang L, Zhao J, Zhang HT*. (2015) miR-1238 inhibits cell proliferation by targeting LHX2 in non-small cell lung cancer. Oncotarget, 6(22):19043-19054. https://doi.org/10.18632/oncotarget.4232
11. Lei Z, Xu G, Wang L, Yang H, Liu X, Zhao J, Zhang HT*. (2014) MiR-142-3p represses TGF-β-induced growth inhibition through repression of TGFβR1 in non-small cell lung cancer. FASEB J, 28(6):2696-2704. https://doi.org/10.1096/fj.13-247288
12. Chen H, Yang T, Lei Z, Wang L, Yang H, Tong X, Yang WT, Zhao J, Gu Y, Chen Y*, Zhang HT*.(2015) RNF111/Arkadia is regulated by DNA methylation and affects TGF-β/Smad signaling associated invasion in NSCLC cells. Lung Cancer, 90(1):32-40. https://doi.org/10.1016/j.lungcan.2015.07.010
13. Yang H, Wang L, Zhao J, Chen Y, Lei Z, Liu X, Xia W, Guo L, Zhang HT*. (2015) TGF-β-activated SMAD3/4 complex transcriptionally upregulates N-cadherin expression in non-small cell lung cancer. Lung Cancer, 87(3):249-257. https://doi.org/10.1016/j.lungcan.2014.12.015
14. Hu H, Xu Z, Li C, Xu C, Lei Z, Zhang HT*, Zhao J*. (2016) MiR-145 and miR-203 represses TGF-β-induced epithelial-mesenchymal transition and invasion by inhibiting SMAD3 in non-small cell lung cancer cells. Lung Cancer, 97:87-94. https://doi.org/10.1016/j.lungcan.2016.04.017
15. Liu RY, Zeng Y, Lei Z, Wang L, Yang H, Liu Z, Zhao J*, Zhang HT*. (2014) JAK/STAT3 signaling is required for TGF-β-induced epithelial-mesenchymal transition in lung cancer cells. Int J Oncol, 44(5):1643-1651. https://doi.org/10.3892/ijo.2014.2310
16. Qian Q, Shi X, Lei Z, Zhan L, Liu RY, Zhao J, Yang B, Liu Z, Zhang HT*. (2014) Methylated +58CpG site decreases DCN mRNA expression and enhances TGF-β/Smad signaling in NSCLC cells with high metastatic potential. Int J Oncol, 44(3):874-882. https://doi.org/10.3892/ijo.2014.2255
17. Chen J, Liu RY, Yang L, Zhao J, Zhao X, Lu D, Yi N, Han B, Chen XF, Zhang K, He J, Lei Z, Zhou Y, Pasche B*, Li X*, Zhang HT*. (2013) A two-SNP IL-6 promoter haplotype is associated with increased lung cancer risk. J Cancer Res Clin Oncol, 139(2):231-242. https://doi.org/10.1007/s00432-012-1314-z
18. Liu XL, Xue BX, Lei Z, Yang DR, Zhang QC, Shan YX*, Zhang HT*. (2013) TGFBR3 co-downregulated with GATA3 is associated with methylation of the GATA3 gene in bladder urothelial carcinoma. Anat Rec (Hoboken), 296(11):1717-1723. https://doi.org/10.1002/ar.22802
19. Ling N, Gu J, Lei Z, Li M, Zhao J, Zhang HT*, Li X*. (2013) microRNA-155 regulates cell proliferation and invasion by targeting FOXO3a in glioma. Oncol Rep, 30(5):2111-2118. https://doi.org/10.3892/or.2013.2685
20. Liu XL, Xiao K, Xue B, Yang D, Lei Z, Shan Y*, Zhang HT*. (2013) Dual role of TGFBR3 in bladder cancer. Oncol Rep, 30(3):1301-1308. https://doi.org/10.3892/or.2013.2599
21. Huang H, Sun P, Lei Z, Li M, Wang Y, Zhang HT*, Liu J*. (2015) miR-145 inhibits invasion and metastasis by directly targeting Smad3 in nasopharyngeal cancer. Tumor Biol, 36(6):4123-4131. https://doi.org/10.1007/s13277-015-3046-6
22. Xiao K, Yu Z, Shi DT, Lei Z, Chen H, Cao J, Tian W, Chen W*, Zhang HT*. (2015) Inactivation of BLU is associated with methylation of Sp1-binding site of BLU promoter in gastric cancer. Int J Oncol, 47(2):621-631. https://doi.org/10.3892/ijo.2015.3032
三、2003-2012年间发表的SCI论文 (* 通讯作者)
1. Liu RY, Song X, Chen P, Lei Z, Miao J, Yi N, Zhang K, Pasche B*, Zhang HT*. (2012) Association between IL6 -174G/C and cancer: A meta-analysis of 105,482 individuals. Exp Ther Med, 3(4):655-664. https://doi.org/10.3892/etm.2012.454
2. Lu F, Zhang HT*. (2011) DNA methylation and nonsmall cell lung cancer. Anat Rec (Hoboken), 294(11):1787-1795. https://doi.org/10.1002/ar.21471
3. Sun J, Lei Z, Liu RY, Lu Y, Zhuang Z, Jiang X, Qian Q, Liu Z, Zhao J*, Zhang HT*. (2011) A haplotype of TGFBR1 is predominantly found in non-small cell lung cancer patients displaying TGFBR1 allelic-specific expression. Oncol Rep, 25(3):685-691. https://doi.org/10.3892/or.2011.1135
4. Liu Z, Li W, Lei Z, Zhao J, Chen XF, Liu R, Peng X, Wu ZH, Chen J, Liu H, Zhou QH*, Zhang HT*. (2010) CpG island methylator phenotype involving chromosome 3p confers an increased risk of non-small cell lung cancer. J Thorac Oncol, 5(6):790-797. https://doi.org/10.1097/jto.0b013e3181d862f5
5. Liu RY, Lei Z, Li W, Xu L, Liu Z, Chen XF, Zhao J*, Zhang HT*. (2009) Infrequently methylated event at sites -181 to -9 within the 5' CpG island of E-cadherin in non-small cell lung cancer. Exp Lung Res, 35(7):541-553. https://doi.org/10.1080/01902140902770016
6. Lei Z, Liu RY, Zhao J, Liu Z, Jiang X, You W, Chen XF, Liu X, Zhang K, Pasche B*, Zhang HT*. (2009) TGFBR1 haplotypes and risk of non-small-cell lung cancer. Cancer Res,69(17):7046-7052. (Highlighted article) https://doi.org/10.1158/0008-5472.CAN-08-4602
7. Valle L, Serena-Acedo T, Liyanarachchi S, Hampel H, Comeras I, Li Z, Zeng Q, Zhang HT, Pennison MJ, Sadim M, Pasche B*, Tanner SM*, de la Chapelle A*. (2008) Germline Allele-specific Expression of TGFBR1 Confers an Increased Risk of Colorectal Cancer. Science, 321 (5894):1361-1365. https://doi.org/10.1126/science.1159397
8. Liu Z, Zhao J, Chen XF, Li W, Liu R, Lei Z, Liu X, Peng X, Xu K, Chen J, Liu H, Zhou QH*, Zhang HT*. (2008) CpG island methylator phenotype involving tumor suppressor genes located on chromosome 3p in non-small cell lung cancer. Lung Cancer, 62(1):15-22. https://doi.org/10.1016/j.lungcan.2008.02.005
9. Zhao J, Liu Z, Li W, Liu X, Chen XF, Zhang HT*. (2008) Infrequently methylated event at sites -362 to -142 in the promoter of TGFβR1 gene in non-small cell lung cancer. J Cancer Res Clin Oncol, 134(8):919-925. https://doi.org/10.1007/s00432-008-0392-4
10. You W, Liu Z, Zhao J, Zheng M, Zheng SY, Liu X, Zhang HT*. (2007) No association between TGFBR1*6A and lung cancer.J Thorac Oncol,2(7):657-659. https://doi.org/10.1097/JTO.0b013e318070ccd7
11. Zhang HT*, Zhao J, Zheng SY, Chen XF. (2005) Is TGFBR1*6A really associated with increased risk of cancer? J Clin Oncol, 23(30):7743-7744. https://doi.org/10.1200/JCO.2005.02.9108
12. Zhang HT*. (2005) Int7G24A variant of the TGFBR1 gene and cancer risk: a meta-analysis of three case-control studies. Lung Cancer, 49(3):419-420. https://doi.org/10.1016/j.lungcan.2005.03.038
13. Chen XF, Zhang HT*, Qi QY, Sun MM, Tao LY. (2005) Expression of E-cadherin and nm23 is associated with the clinicopathological factors of human non-small cell lung cancer in China. Lung Cancer, 48(1):69-76. https://doi.org/10.1016/j.lungcan.2004.09.009
14. Zhang HT, Chen XF, Wang MH, Wang JC, Qi QY, Zhang RM, Xu WQ, Fei QY, Wang F, Cheng QQ, Chen F, Zhu CS, Tao SH, Luo Z*. (2004) Defective expression of transforming growth factor β receptor type II is associated with CpG methylated promoter in primary non-small cell lung cancer. Clin Cancer Res, 10(7):2359-2367. https://doi.org/10.1158/1078-0432.ccr-0959-3
15. Zhang HT, Fei QY, Chen F, Qi QY, Zou W, Wang JC, Zhang RM, Tao SH, Chen XF, Luo ZW*. (2003) Mutational analysis of the transforming growth factor beta receptor type I gene in primary non-small cell lung cancer. Lung Cancer, 40(3):281-287. https://doi.org/10.1016/S0169-5002(03)00121-1
1. 博士研究生招生(硕博连读、申请-考核制):
基础医学(1001):医学细胞与分子生物学(1001Z2)
2. 硕士研究生招生(免试推荐、公开招考):
基础医学(1001):人类遗传学/医学细胞生物学(研究方向)
张洪涛,教授、博士生导师,国家教育部新世纪优秀人才支持计划获得者,苏州大学东吴学者。现任苏州大学基础医学院副院长、医学遗传学系系主任(兼)、苏州大学癌症分子遗传学实验室主任、苏州市癌症分子遗传学重点实验室主任。
立足国内发展,10年来一直围绕非小细胞肺癌的遗传学与表观遗传学的致病机制研究开展工作。主持承担 9 项国家自然科学基金项目(8项已结题)、2项教育部人才项目(已结题)、2项江苏省自然科学基金(已结题)和1项苏州市重点实验室建设项目(已结题)和2项横向课题(在研)。以通讯作者身份在J Clin Oncol、Cancer Res、EMBO Reports、Cell Reports、Oncogene、FASEB J、Semin Cancer Biol 等国际著名期刊上发表30余篇SCI论文,他引1,000余次。2008年获江苏省科技进步奖三等奖1项(第1完成人),2014年获江苏省科学技术奖二等奖1项(第1完成人),2021年获江苏省科学技术奖三等奖1项(第1完成人),荣获2022年度江苏省行业领域(基础研究)十大科技进展(第1完成人)。现任中国抗癌协会非小细胞肺癌专业委员会常务委员、中国抗癌协会肿瘤转移专业委员会委员、Oncology Letters 和 Thoracic Cancer编委、《中国肺癌杂志》常务编委。NEJM、JAMA、Cancer Res、Oncogene、Int J Cancer、Lung Cancer等国际期刊的审稿人。
1. 肿瘤细胞与分子生物学(肺癌的TGF-β/Smads信号通路调控,蛋白翻译后修饰PTM)
2. 肿瘤表观遗传学(肺癌的非编码RNA调控机制、肺癌的RNA m6A甲基化调控机制)
一、研究内容:
课题组以研究TGF-β/Smads信号通路在肺癌发生发展、恶性转化、侵袭与转移中的作用机制为特色,密切围绕以下几个方面开展肺癌的生物学、分子遗传学与表观遗传学的调控机理研究:
1)非编码RNA(miRNA、lncRNA、circRNA)在TGF-β诱导非小细胞肺癌上皮-间质转化(EMT)中的表观调控作用机制
2)TGF-β/Smads与IL-6/JAK/STAT信号通路在非小细胞肺癌EMT过程中的协同作用机制
3)Decorin (TGF-β inhibitor)基因甲基化调控的非小细胞肺癌转移的分子机制
4)TGF-β/Smads信号通路受体基因启动子区变异与非小细胞肺癌发生发展关系
5)SOX2-TIF1γ轴向调控TGF-β诱导的EMT和NSCLC细胞的侵袭转移的机制
6)TIF1γ 泛素化TAF15调控肺腺癌细胞EMT和侵袭转移的作用机制
二、主持课题:
1. 国家自然科学基金(82273372)“TRIM33/TAF15/IL6轴调控抑制肺腺癌细胞EMT和侵袭转移的作用机制” 2023.1-2026.12;在研
2. 国家自然科学基金(82073198)“心肌素促进非小细胞肺癌侵袭转移的作用机制” 2021.1-2024.12;已结题
3. 国家自然科学基金(81872343)“Circ-PTK2/miR-429/TIF1γ轴调控TGF-β诱导的NSCLC细胞EMT的机制” 2019.1-2022.12;已结题
4. 国家自然科学基金(81672277)“lncRNA XIST/miR-367/ZEB2轴促进TGF-β诱导非小细胞肺癌EMT的表观调控机制” 2017.1-2020.12;已结题
5. 国家自然科学基金(81372277)“TGF-β/Smads与IL-6/JAK/STAT信号通路在非小细胞肺癌上皮-间质转化(EMT)过程中协同作用的机制” 2014.1-2017.12;已结题
6. 国家自然科学基金(81171894)“基于Decorin基因甲基化调控的非小细胞肺癌转移的分子机制” 2012.1-2015.12;已结题
7. 国家自然科学基金(30973425)“基于DNA甲基化的非小细胞肺癌中TGFβR3基因失活的表观遗传调控机制研究” 2010.1-2012.12;已结题
8. 国家自然科学基金(30672400)“TGFBRI基因启动子区变异与非小细胞肺癌发生发展关系的研究” 2007.1-2009.12;已结题
9. 国家自然科学基金(30400533)“非小细胞肺癌患者外周血DNA甲基化异常基因的研究及其临床意义” 2005.1-2007.12;已结题
10. 国家教育部 “新世纪优秀人才支持计划” 项目(NCET-09-0165)“非小细胞肺癌的分子遗传学和表观遗传学的致病机制研究” 2010.1-2012.12;已结题
11. 江苏省自然科学基金(BK2008162)“hOGG1基因的表观修饰与非小细胞肺癌发生发展关系的研究” 2008.6-2011.6;已结题
12. 江苏省科技厅青年科技创新人才学术带头人项目(BK2004402)“非小细胞肺癌中癌相关基因的DNA甲基化研究及其临床意义” 2005.1-2006.12;已结题
13. 教育部 “留学回国人员科研启动基金”(教外司留[2008]890号),已结题
14. 苏州市癌症分子遗传学重点实验室建设项目(SZS201209),2012.7-2015.6;已结题
讲 师:刘霞
副研究员:雷哲
博士生(16人):石浩(2025级),尹小屿(2024级),胡凌吉(2023级),王永(2022级),靳二锁(2021级),孙泽龙(2020级),王昭(2019级),苏志越(2018级),王胜洁(2017级),童新(2016级),汪龙强(2014级),李畅(2013级),杨海平(2012级)、雷哲(2011级)、刘仍允(2009级)、刘泽毅(2008级)
硕士生(48人):丁乙、许展慎(2025级),张志豪(2024级),王名宇、潘利娜(2023级),梁鹏、石浩(2022级),胡凌吉、吴高添(2021级),万立、王菲菲、尹小屿(2020级),王宇鑫、陈小燕(2019级),靳二锁、王永(2018级),孙泽龙、张伟伟 (2017级),王昭、张翠娟(2016级),苏志越、张滢溪(2015级),童新、孙天锦(2014级),万亮、杨庆慧、杨天杰(2013级),陈红兵、占雷(2012级),石祥广、徐桂丽(2011级),汪龙强、杨海平、曾园园(2010级),卢芳、宋晓雪(2009级),钱乾、孙金霞(2008级),蒋谢芳(2007级),雷哲、刘仍允、曹志飞、彭晓蓓(2006级),刘泽毅、李雯雯(2005级),尤伟明、刘霞、许林燕(2004级)
P.S.
刘泽毅,曾为美国 Kentucky 大学博士后,现为苏州大学附一院呼吸科 研究员;国家自然科学基金青年、面上项目获得者。
刘仍允,曾为美国 Johns Hopkins 大学医学院博士后,现为中山大学附一院精准医学研究院 研究员;国家自然科学基金优秀青年科学基金、面上项目获得者。
雷 哲,曾为美国 National Jewish Health 访问学者,现为苏州大学附一院病理科 副研究员;国家自然科学基金青年、面上项目获得者。
李 畅,曾为芬兰 Helsinki 大学访问学者,现为苏州大学附一院胸外科 主任医师、副教授;国家自然科学基金面上项目获得者。
汪龙强,现为美国 MD Anderson 癌症中心 博士后研究员
石祥广,现为复旦大学附属华山医院皮肤科 副研究员;国家自然科学基金优秀青年科学基金、面上项目获得者。
童 新,现为苏州大学附一院胸外科 助理研究员;国家自然科学基金青年基金项目获得者。
王胜洁,现为南京医科大学康达学院 副教授;国家自然科学基金青年基金项目获得者。
苏志越,现为苏州大学附一院病理科 博士后研究员;国家自然科学基金青年基金项目获得者。
王 昭,现为苏州大学附一院肿瘤科 助理研究员。
靳二锁,现为嘉兴大学医学院 副教授。
(1). 讲授医学本科生《医学遗传学》和卓越医师班《医学基础II》、生物技术专业的《医学遗传学》(双语)、研究生《医学分子遗传学》以及留学生的《Medical Genetics》等课程。(2). 主持承担苏州大学《医学遗传学》双语教学示范课程建设1项。(3).《Textbook of Medical Genetics》(双语教材) 编委,负责其中第10、16章节的编写。(4). 近五年来,共指导博士生6名、硕士生16名、“莙政学者”1名。
一、2023-至今发表的SCI论文(* 通讯作者)
1. Jin E, Wang S, Chen D, Wang JP, Zeng Y, Sun R*, Zhang HT*. (2024) P4HA2 activates mTOR via hydroxylation and targeting P4HA2-mTOR inhibits lung adenocarcinoma cell growth. Oncogene, 43(24):1813-1823. https://doi.org/10.1038/s41388-024-03032-1
2. Wang Z, Lei Z, Wang Y, Wang S, Wang JP, Jin E, Liu X, Sun R*, Zhang HT*. (2024) Bone-metastatic lung adenocarcinoma cells bearing CD74-ROS1 fusion interact with macrophages to promote their dissemination. Oncogene, 43(28):2215-2227. https://doi.org/10.1038/s41388-024-03072-7
二、2013-2022年间发表的SCI论文(* 通讯作者)
1. Su Z, Sun Z, Wang Z, Wang S, Wang Y, Jin E, Li C, Zhao J, Liu Z, Zhou Z, Wang Y, Chen X, Liu X, Lei Z*, Zhang HT*. (2022) TIF1γ inhibits lung adenocarcinoma EMT and metastasis by interacting with the TAF15/TBP complex. Cell Reports, 41(3):111513. (Research Article) https://doi.org/10.1016/j.celrep.2022.111513
2. Wang S, Sun Z, Lei Z*, Zhang HT*. (2022) RNA-binding proteins and cancer metastasis. Semin Cancer Biol, 86(Pt 2):748-768. (Invited Review, IF:17.012) https://doi.org/10.1016/j.semcancer.2022.03.018
3. Wang Z, Chen J, Wang S, Sun Z, Lei Z, Zhang HT*, Huang J*. (2022) RGS6 suppresses TGF-β-induced epithelial–mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4. Cell Death & Disease, 13(7):656. https://doi.org/10.1038/s41419-022-05093-0
4. Sun Z, Su Z, Zhou Z, Wang S, Wang Z, Tong X, Li C, Wang Y, Chen X, Lei Z, Zhang HT*. (2022) RNA demethylase ALKBH5 inhibits TGF-β-induced EMT by regulating TGF-β/SMAD signaling in non-small cell lung cancer. FASEB J, 36(5):e22283. (Research Article) https://doi.org/10.1096/fj.202200005RR
5. Wang S, Tong X, Li C, Jin E, Su Z, Sun Z, Zhang W, Lei Z, Zhang HT*. (2021) Quaking 5 suppresses TGF-β-induced EMT and cell invasion in lung adenocarcinoma. EMBO Reports, 22(6):e52079. (Research Article) https://doi.org/10.15252/embr.202052079
6. Tong X, Wang S, Lei Z, Li C, Zhang C, Su Z, Liu X, Zhao J, Zhang HT*. (2020) MYOCD and SMAD3/SMAD4 form a positive feedback loop and drive TGF-β-induced epithelial-mesenchymal transition in non-small cell lung cancer. Oncogene, 39(14):2890-2904. https://doi.org/10.1038/s41388-020-1189-4
7. Wang L, Tong X, Zhou Z, Wang S, Lei Z, Zhang T, Liu Z, Zeng Y, Li C, Zhao J, Su Z, Zhang C, Liu X, Xu G*, Zhang HT*. (2018) Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by controlling TIF1γ in non-small cell lung cancer. Mol Cancer, 17(1):140 (p1-18).(Research Article) https://doi.org/10.1186/s12943-018-0889-7
8. Li C, Wan L, Liu Z, Xu G, Wang S, Su Z, Zhang Y, Zhang C, Liu X, Lei Z*, Zhang HT*. (2018) Long non-coding RNA XIST promotes TGF-β-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer. Cancer Lett, 418:185-195. https://doi.org/10.1016/j.canlet.2018.01.036
9. Wang L, Yang H, Lei Z, Zhao J, Chen Y, Chen P, Li C, Zeng Y, Liu Z, Liu X, Zhang HT*. (2016) Repression of TIF1γ by SOX2 promotes TGF-β-induced epithelial-mesenchymal transition in non-small-cell lung cancer. Oncogene,35(7):867-877. https://doi.org/10.1038/onc.2015.141
10. Shi X, Zhan L, Xiao C, Lei Z, Yang H, Wang L, Zhao J, Zhang HT*. (2015) miR-1238 inhibits cell proliferation by targeting LHX2 in non-small cell lung cancer. Oncotarget, 6(22):19043-19054. https://doi.org/10.18632/oncotarget.4232
11. Lei Z, Xu G, Wang L, Yang H, Liu X, Zhao J, Zhang HT*. (2014) MiR-142-3p represses TGF-β-induced growth inhibition through repression of TGFβR1 in non-small cell lung cancer. FASEB J, 28(6):2696-2704. https://doi.org/10.1096/fj.13-247288
12. Chen H, Yang T, Lei Z, Wang L, Yang H, Tong X, Yang WT, Zhao J, Gu Y, Chen Y*, Zhang HT*.(2015) RNF111/Arkadia is regulated by DNA methylation and affects TGF-β/Smad signaling associated invasion in NSCLC cells. Lung Cancer, 90(1):32-40. https://doi.org/10.1016/j.lungcan.2015.07.010
13. Yang H, Wang L, Zhao J, Chen Y, Lei Z, Liu X, Xia W, Guo L, Zhang HT*. (2015) TGF-β-activated SMAD3/4 complex transcriptionally upregulates N-cadherin expression in non-small cell lung cancer. Lung Cancer, 87(3):249-257. https://doi.org/10.1016/j.lungcan.2014.12.015
14. Hu H, Xu Z, Li C, Xu C, Lei Z, Zhang HT*, Zhao J*. (2016) MiR-145 and miR-203 represses TGF-β-induced epithelial-mesenchymal transition and invasion by inhibiting SMAD3 in non-small cell lung cancer cells. Lung Cancer, 97:87-94. https://doi.org/10.1016/j.lungcan.2016.04.017
15. Liu RY, Zeng Y, Lei Z, Wang L, Yang H, Liu Z, Zhao J*, Zhang HT*. (2014) JAK/STAT3 signaling is required for TGF-β-induced epithelial-mesenchymal transition in lung cancer cells. Int J Oncol, 44(5):1643-1651. https://doi.org/10.3892/ijo.2014.2310
16. Qian Q, Shi X, Lei Z, Zhan L, Liu RY, Zhao J, Yang B, Liu Z, Zhang HT*. (2014) Methylated +58CpG site decreases DCN mRNA expression and enhances TGF-β/Smad signaling in NSCLC cells with high metastatic potential. Int J Oncol, 44(3):874-882. https://doi.org/10.3892/ijo.2014.2255
17. Chen J, Liu RY, Yang L, Zhao J, Zhao X, Lu D, Yi N, Han B, Chen XF, Zhang K, He J, Lei Z, Zhou Y, Pasche B*, Li X*, Zhang HT*. (2013) A two-SNP IL-6 promoter haplotype is associated with increased lung cancer risk. J Cancer Res Clin Oncol, 139(2):231-242. https://doi.org/10.1007/s00432-012-1314-z
18. Liu XL, Xue BX, Lei Z, Yang DR, Zhang QC, Shan YX*, Zhang HT*. (2013) TGFBR3 co-downregulated with GATA3 is associated with methylation of the GATA3 gene in bladder urothelial carcinoma. Anat Rec (Hoboken), 296(11):1717-1723. https://doi.org/10.1002/ar.22802
19. Ling N, Gu J, Lei Z, Li M, Zhao J, Zhang HT*, Li X*. (2013) microRNA-155 regulates cell proliferation and invasion by targeting FOXO3a in glioma. Oncol Rep, 30(5):2111-2118. https://doi.org/10.3892/or.2013.2685
20. Liu XL, Xiao K, Xue B, Yang D, Lei Z, Shan Y*, Zhang HT*. (2013) Dual role of TGFBR3 in bladder cancer. Oncol Rep, 30(3):1301-1308. https://doi.org/10.3892/or.2013.2599
21. Huang H, Sun P, Lei Z, Li M, Wang Y, Zhang HT*, Liu J*. (2015) miR-145 inhibits invasion and metastasis by directly targeting Smad3 in nasopharyngeal cancer. Tumor Biol, 36(6):4123-4131. https://doi.org/10.1007/s13277-015-3046-6
22. Xiao K, Yu Z, Shi DT, Lei Z, Chen H, Cao J, Tian W, Chen W*, Zhang HT*. (2015) Inactivation of BLU is associated with methylation of Sp1-binding site of BLU promoter in gastric cancer. Int J Oncol, 47(2):621-631. https://doi.org/10.3892/ijo.2015.3032
三、2003-2012年间发表的SCI论文 (* 通讯作者)
1. Liu RY, Song X, Chen P, Lei Z, Miao J, Yi N, Zhang K, Pasche B*, Zhang HT*. (2012) Association between IL6 -174G/C and cancer: A meta-analysis of 105,482 individuals. Exp Ther Med, 3(4):655-664. https://doi.org/10.3892/etm.2012.454
2. Lu F, Zhang HT*. (2011) DNA methylation and nonsmall cell lung cancer. Anat Rec (Hoboken), 294(11):1787-1795. https://doi.org/10.1002/ar.21471
3. Sun J, Lei Z, Liu RY, Lu Y, Zhuang Z, Jiang X, Qian Q, Liu Z, Zhao J*, Zhang HT*. (2011) A haplotype of TGFBR1 is predominantly found in non-small cell lung cancer patients displaying TGFBR1 allelic-specific expression. Oncol Rep, 25(3):685-691. https://doi.org/10.3892/or.2011.1135
4. Liu Z, Li W, Lei Z, Zhao J, Chen XF, Liu R, Peng X, Wu ZH, Chen J, Liu H, Zhou QH*, Zhang HT*. (2010) CpG island methylator phenotype involving chromosome 3p confers an increased risk of non-small cell lung cancer. J Thorac Oncol, 5(6):790-797. https://doi.org/10.1097/jto.0b013e3181d862f5
5. Liu RY, Lei Z, Li W, Xu L, Liu Z, Chen XF, Zhao J*, Zhang HT*. (2009) Infrequently methylated event at sites -181 to -9 within the 5' CpG island of E-cadherin in non-small cell lung cancer. Exp Lung Res, 35(7):541-553. https://doi.org/10.1080/01902140902770016
6. Lei Z, Liu RY, Zhao J, Liu Z, Jiang X, You W, Chen XF, Liu X, Zhang K, Pasche B*, Zhang HT*. (2009) TGFBR1 haplotypes and risk of non-small-cell lung cancer. Cancer Res,69(17):7046-7052. (Highlighted article) https://doi.org/10.1158/0008-5472.CAN-08-4602
7. Valle L, Serena-Acedo T, Liyanarachchi S, Hampel H, Comeras I, Li Z, Zeng Q, Zhang HT, Pennison MJ, Sadim M, Pasche B*, Tanner SM*, de la Chapelle A*. (2008) Germline Allele-specific Expression of TGFBR1 Confers an Increased Risk of Colorectal Cancer. Science, 321 (5894):1361-1365. https://doi.org/10.1126/science.1159397
8. Liu Z, Zhao J, Chen XF, Li W, Liu R, Lei Z, Liu X, Peng X, Xu K, Chen J, Liu H, Zhou QH*, Zhang HT*. (2008) CpG island methylator phenotype involving tumor suppressor genes located on chromosome 3p in non-small cell lung cancer. Lung Cancer, 62(1):15-22. https://doi.org/10.1016/j.lungcan.2008.02.005
9. Zhao J, Liu Z, Li W, Liu X, Chen XF, Zhang HT*. (2008) Infrequently methylated event at sites -362 to -142 in the promoter of TGFβR1 gene in non-small cell lung cancer. J Cancer Res Clin Oncol, 134(8):919-925. https://doi.org/10.1007/s00432-008-0392-4
10. You W, Liu Z, Zhao J, Zheng M, Zheng SY, Liu X, Zhang HT*. (2007) No association between TGFBR1*6A and lung cancer.J Thorac Oncol,2(7):657-659. https://doi.org/10.1097/JTO.0b013e318070ccd7
11. Zhang HT*, Zhao J, Zheng SY, Chen XF. (2005) Is TGFBR1*6A really associated with increased risk of cancer? J Clin Oncol, 23(30):7743-7744. https://doi.org/10.1200/JCO.2005.02.9108
12. Zhang HT*. (2005) Int7G24A variant of the TGFBR1 gene and cancer risk: a meta-analysis of three case-control studies. Lung Cancer, 49(3):419-420. https://doi.org/10.1016/j.lungcan.2005.03.038
13. Chen XF, Zhang HT*, Qi QY, Sun MM, Tao LY. (2005) Expression of E-cadherin and nm23 is associated with the clinicopathological factors of human non-small cell lung cancer in China. Lung Cancer, 48(1):69-76. https://doi.org/10.1016/j.lungcan.2004.09.009
14. Zhang HT, Chen XF, Wang MH, Wang JC, Qi QY, Zhang RM, Xu WQ, Fei QY, Wang F, Cheng QQ, Chen F, Zhu CS, Tao SH, Luo Z*. (2004) Defective expression of transforming growth factor β receptor type II is associated with CpG methylated promoter in primary non-small cell lung cancer. Clin Cancer Res, 10(7):2359-2367. https://doi.org/10.1158/1078-0432.ccr-0959-3
15. Zhang HT, Fei QY, Chen F, Qi QY, Zou W, Wang JC, Zhang RM, Tao SH, Chen XF, Luo ZW*. (2003) Mutational analysis of the transforming growth factor beta receptor type I gene in primary non-small cell lung cancer. Lung Cancer, 40(3):281-287. https://doi.org/10.1016/S0169-5002(03)00121-1
1. 博士研究生招生(硕博连读、申请-考核制):
基础医学(1001):医学细胞与分子生物学(1001Z2)
2. 硕士研究生招生(免试推荐、公开招考):
基础医学(1001):人类遗传学/医学细胞生物学(研究方向)