甲状腺疾病研究室
甲状腺疾病研究中心依托本研究所附属医院丰富的临床甲状腺病诊疗经验及病理资源，围绕甲状腺疾病开展基础及临床应用研究。本研究室成员包含一线的临床医生以及来自各个学科的科研工作者，旨在从实际临床问题出发，通过基础研究阐明甲状腺疾病发生的机理，推进甲状腺诊治事业的发展。
为阐明甲状腺病变的病因、为临床提供有价值的诊断及干预手段，研究中心致力于探索驱动甲状腺肿瘤恶变的新型分子靶标；甲状腺癌抗放射性碘-131治疗的分子机制及逆转方法；甲状腺肿瘤代谢及表观遗传学调控机制等方面研究。中心在积极开展基础研究的同时注重临床转换，已在临床开展细针穿刺联合癌基因检测鉴别甲状腺结节良恶性技术服务，并建立标准化、专业化的甲状腺疾病样本库，努力把该中心打造成国内有影响力的甲状腺疾病研究平台及科研创新团队。
研究室负责人
张莉，副研究员，硕士生导师
研究室主要成员
包建东，主任医师，内科
俞惠新，研究员，硕士生导师
邬宏恂，主任医师，超声科
邹贤，副主任医师，外科
程献，研究实习员
徐石宸，研究实习员
吴静，实验技术员
郑江峡，在读硕士研究生
王晓雯，在读硕士研究生
吴立颖，在读硕士研究生
电 话：0510-85514482-3526
传 真：0510-85513113
E-mail: zhangli@jsinm.org
研究方向
1．BRAF、RAS等基因突变驱动甲状腺肿瘤恶变的新型分子机制
2．碘难治性甲状腺癌发生的分子机制及逆转研究
3．小分子化合物抑制甲状腺癌生长、转移、失分化的药理学研究
4．甲状腺病变良恶性鉴别的分子病理相关marker的基础及应用研究
5．肿瘤微环境与甲状腺癌发生发展关系的研究
6．其他临床甲状腺病变的病因、诊断及干预手段的研究
承担科研项目
1．2020.1～2023.12 国家自然科学基金面上项目“肿瘤炎性微环境BRAF-组胺/组胺受体正反馈环路促进甲状腺乳头状癌失分化的新机制（81972503）”
2．2019.1～2020.12 无锡市卫计委青年项目“ZNF148多态性检测用于甲状腺结节良恶性鉴别的研究（Q201836）”
3．2017.1～2019.12 国家自然科学基金“表观遗传调节子MKL1介导转录复合物组装促甲状腺癌侵袭转移的新机制（81602352）”
4．2017.1～2019.12 国家自然科学基金“甲状腺癌BRAF V600E在DRP1介导的线粒体稳态中的调控新机制研究（81602353）”
5．2017.1～2018.12 无锡市卫计委青年项目“MEF2A评估甲状腺癌复发转移风险的研究（Q201608）”
6．2015.1～2017.12 国家自然科学基金“转录因子MEF2A介导BRAF突变型甲状腺乳头状癌发生发展的新机制（81402214）”
7．2014.1～2016.12 国家卫生部科研基金“姜黄素对甲状腺癌放射性碘-131 治疗的增敏研究（W201304）”
8．2010.7～2013.6 江苏省自然基金“MEF2A胞内降解机制及Pro279Leu突变对其神经保护功能影响的实验研究(BK2010156)”
9．2006.7～2009.6 江苏省自然基金“红景天苷抗β淀粉样蛋白诱发神经元细胞凋亡的作用及机制(BK2006026)”
10．2009.1～2011.12 国家自然科学基金“斑块显像剂评估肿瘤坏死因子抑制剂治AD的实验研究（30870727）”
11．2010.10～2013. 9 江苏省卫生厅科技项目“放疗增敏剂在抗碘-131甲状腺癌治疗中的应用（H2010027）”
代表性研究论文
1) Xu S, Pan J, Cheng X, Zheng J, Wang X, Guan H, et al. Diallyl trisulfide, a H2 S donor, inhibits cell growth of human papillary thyroid carcinoma KTC-1 cells through a positive feedback loop between H2 S and cystathionine-gamma-lyase. Phytotherapy Research. 2020. IF: 3.766.
2) Zheng J, Cheng X, Xu S, Zhang L, Pan J, Yu H, et al. Diallyl trisulfide induces G2/M cell-cycle arrest and apoptosis in anaplastic thyroid carcinoma 8505C cells. Food Function. 2019;10(11):7253-61. IF: 3.241.
3) Wang H, Cheng X, Zhang L, Xu S, Zhang Q, Lu R. A surface-layer protein from Lactobacillus acidophilus NCFM induces autophagic death in HCT116 cells requiring ROS-mediated modulation of mTOR and JNK signaling pathways. Food Funct. 2019;10(7):4102-12. IF: 3.241.
4) Cheng X, Xu S, Pan J, Zheng J, Wang X, Yu H, et al. MKL1 overexpression predicts poor prognosis in patients with papillary thyroid cancer and promotes nodal metastasis. Journal of Cell Science. 2019;132(16). IF: 4.517.
5) Gao Y, Yang F, Yang X, Zhang L, Yu H, Cheng X, Xu S, Pan J, Wang K, Li P. Mitochondrial metabolism is inhibited by the HIF1α-MYC-PGC-1β axis in BRAF V600E thyroid cancer. The FEBS Journal. 2019. IF: 4.530.
6) Cheng X.#, Yao X.#, Xu S., Pan J., Yu H., Bao J., Guan H., Lu R., Zhang L.*. Punicalagin induces senescent growth arrest in human papillary thyroid carcinoma BCPAP cells via NF-kappaB signaling pathway. Biomedicine & pharmacotherapy. 2018; 103, 490-498. IF: 3.457.
7) Zhang L., Cheng X., Xu S., Bao J., and Yu H. Curcumin induces endoplasmic reticulum stress-associated apoptosis in human papillary thyroid carcinoma BCPAP cells via disruption of intracellular calcium homeostasis. Medicine (Baltimore). 2018; 97, e11095. IF: 2.028.
8) Xu S., Zhang L., Cheng X., Yu H., Bao J., and Lu R. Capsaicin inhibits the metastasis of human papillary thyroid carcinoma BCPAP cells through the modulation of the TRPV1 channel. Food & Function. 2018; 9, 344-354. IF: 3.289.
9) Pan, J., Zhang, L., Xu, S., Cheng, X., Yu, H., Bao, J., and Lu, R. Induction of Apoptosis in Human Papillary-Thyroid-Carcinoma BCPAP Cells by Diallyl Trisulfide through Activation of the MAPK Signaling Pathway. Journal of Agricultural and Food Chemistry. 2018; 66, 5871-5878. IF: 3.412.
10) Yao X., Cheng X., Zhang L., Yu H., Bao J., Guan H., Lu R. *, Punicalagin promotes cell death by triggering ATM-mediated DNA damage response in human papillary thyroid carcinoma BCPAP cells, Nutrition Research. 2017, 47 63-71 I F:2.707.
11) Cheng X., Gao Y., Yao X., Yu H., Bao J., Guan H., Sun Y. & Zhang L.*. Punicalagin induces apoptosis-independent autophagic cell death in human papillary thyroid carcinoma BCPAP cells. RSC Advances. 2016, 6:68485-68493. I F: 2.936.
12) Zhang L., Cheng X., GaoY., Zhang C., Bao J., Guan H., Yu H., Lu R., Xu Q., Sun Y., Curcumin inhibits metastasis in human papillary thyroid carcinoma BCPAP cells via down-regulation of the TGF-beta/Smad2/3 signaling pathway, Experimental Cell Research. 341, 157-165, 2016.IF: 3.309.
13) Zhang L., Cheng, Y. Gao, J. Bao, H. Guan, R. Lu, H. Yu, Q. Xu, Y. Sun, Induction of ROS-independent DNA damage by curcumin leads to G2/M cell cycle arrest & apoptosis in human papillary thyroid carcinoma BCPAP cells. Food & Function. 7, 315-325, 2016. IF: 3.289.
14) Zeng S#, Yang Y#, Cheng X#, Zhou B#, Li P, Zhao Y, Kong X*, Xu Y*. HIC1 epigenetically represses CIITA transcription in B lymphocytes. Biochimica et Biophysica Acta-Gene Regulatory Mechanisms. 2016, 1859, 1481-1489. IF: 5.179.
15) Zhengping Chen, Jie Tang, Chunyi Liu, Xiaomin Li, Hongbo Huang, Xijie Xu, Huixin Yu. Effects of anesthetics on vesicular monoamine transporter type 2 binding to 18F-FP-(+)-DTBZ: a biodistribution study in rat brain. Nuclear Medicine & Biology. 2016, 43, 124-129. IF: 2.203.
16) Zhang, L., Cheng, X., Gao, Y., Zheng, J., Xu, Q., Sun, Y., Guan, H., Yu, H. *, Sun, Z*. Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells. Food & Function. 2015, 6, 3464-3472. IF: 2.791.
17) Cheng X#, Yang Y#, Fan Z, Yu L, Bai H, Zhou B, Wu X, Xu H, Fang M, Shen A, Chen Q & Xu Y*. MKL1 potentiates lung cancer cell migration & invasion by epigenetically activating MMP9 transcription. Oncogene. 2015, 34, 5570-5581. IF: 8.459.
18) Zhang L.*,#（第一作者兼通讯作者）, Sun Y#., Fei M.-J., Tan C., Sun W., Wu J., Bao J.-D., Xu Q.*, Yu H.-X*. Disruption of chaperone-mediated autophagy-dependent degradation of MEF2A by oxidative stress-induced lysosome destabilization. Autophagy. 2014, 10, 1015-1035. IF: 11.100.
19) Tan, C., Zhang, L.(co-firstauthor), Cheng, X., Lin, X.F., Lu, R.R., Bao, J.D., Yu, H.X., Curcumin inhibits hypoxia-induced migration in K1 papillary thyroid cancer cells. Experimental biology and medicine (Maywood). 2014, 240, 925-935. IF:2.413.
20) Y. Cheng, L. Zhang, W. Sun, J. Tang, Z. Lv, Z. Xu, H. Yu, Protective effects of a wheat germ peptide (RVF) against H2O 2-induced oxidative stress in human neuroblastoma cells. Biotechnology Letters. 2014, 36, 1615-1622. IF:1.846.
21) Zhang C.-Y.#, Zhang L.# (co-first author), Yu H.-X., Bao J.-D., Lu R.-R*. Curcumin inhibits the metastasis of K1 papillary thyroid cancer cells via modulating E-cadherin & matrix metalloproteinase-9 expression. Biotechnology Letters. 35, 995-1000, 2013. IF: 1.846.
22) Zhang C.-Y.#, Zhang L.# (co-first author), Yu H.-X., Bao J.-D., Sun Z, Lu R.-R*. Curcumin inhibits invasion & metastasis in K1 papillary thyroid cancer cells. Food Chemistry. 2013, 139, 1021-1028. IF: 4.946.
23) Guo WJ#, Zhang YM#, Zhang L, Huang B, Tao FF, Chen W, Guo ZJ, Xu Q*, Sun Y. Novel monofunctional platinum (II) complex Mono-Pt induces apoptosis-independent autophagic cell death in human ovarian carcinoma cells, distinct from cisplatin. Autophagy. 2013, 11, 9, 996-1008. IF:11.100.
24) Jin M.M., Zhang L.,Yu H.X., Meng J., Sun Z. & Lu R.R*. Protective effect of whey protein hydrolysates on H2O2-induced PC12 cells oxidative stress via a mitochondria-mediated pathway. Food Chemistry. 2013, 141, 847-852, IF: 4.946.
25) Chunxiong Lu, Quanfu Jiang, Minjin Hu, Cheng Tan, Yu Ji, Huixin Yu*& Zichun Hua*. Preliminary Biological Evaluation of Novel Tc-99m-Cys-Annexin A5 as a Apoptosis Imaging Agent. Molecules. 2013, 18:6908-6918. IF: 3.098.
26) Zhang Q.X., Ling Y.F., Sun Z., Zhang L.,Yu H.X., Kamau S.M., Lu R.R*. Protective effect of whey protein hydrolysates against hydrogen peroxide-induced oxidative stress on PC12 cells. Biotechnology Letters. 2012, 34, 2001-2006. IF: 1.846.
27) Song F.#, Zhang L.# (co-first author), Yu H.-X., Lu R.-R., Bao J.-D., Sun Z*. The mechanism underlying proliferation-inhibitory & apoptosis-inducing effects of curcumin on papillary thyroid cancer cells. Food Chemistry. 132, 43-50, 2012. IF: 4.946.
28) Cheng ZP, Liu CY, Li XM, Tang J, Tan C, Huang HB, Yu HX, Luo SN. Semi-automated synthesis, validation & microPET imaging of 18F-fp-DTBZ as a vesicular monamine transporter ligand. Nuclear Science & Techniques. 2012, 23, 40-46. IF: 1.085.
29) Zhao X.-C.#, Zhang L.# (co-first author) Yu H.-X., Sun Z., Lin X.-F., Tan C., Lu R.-R*. Curcumin protects mouse neuroblastoma Neuro-2A cells against hydrogen-peroxide-induced oxidative stress. Food Chemistry. 2011, 129, 387-94. IF: 4.946.
30) Zhang L., Yu H.*, Zhao X., Lin X., Tan C., Cao G., Wang Z. Neuroprotective effects of salidroside against beta-amyloid-induced oxidative stress in SH-SY5Y human neuroblastoma cells. Neurochemistry international, 2010, 57, 547-55. IF: 3.603.
31) Zhang L., Yu H.*, Song C., Lin X., Chen B., Tan C., Cao G., Wang Z. Expression, purification, & characterization of recombinant human [beta]-amyloid42 peptide in Escherichia coli. Protein Expression and Purification. 2009, 64, 55-62, IF: 1.338.
32) Zhang L., Yu H.*, Sun Y., Lin X., Chen B., Tan C., Cao G., Wang Z. Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells. European Journal of Pharmacology. 2007, 564, 18-25. IF: 3.040.
33) Zhang L., Dong Y., Sun Y., Chen T., Xu Q*. Role of four major components in the effect of Si-Ni-San, a traditional Chinese prescription, against contact sensitivity in mice. Journal of Pharmacy and Pharmacology. 2006, 58, 1257-64. IF: 2.309.
34) Zhang L, Sun Y, Chen T, Xu Q*. Selective depletion of glycyrrhizin from Si-Ni-San, a traditional Chinese prescription, blocks its effect on contact sensitivity in mice & recovers adhesion & metalloproteinases production of T lymphocytes. International Immunopharmacology. 2005, 5, 1193-204. IF: 2.417.
35) Zhang QX, Jin MM, Zhang L, Yu HX, Sun Z, Lu RR. Hydrophobicity of whey protein hydrolysates enhances the protective effect against oxidative damage on PC 12 cells. Journal of Dairy Research. 2015, 82, 1-7. IF:1.170.
36) Li J., Chen J., Gui C., Zhang L., Qin Y., Xu Q., Zhang J., Liu H., Shen X.*, Jiang H*. Discovering novel chemical inhibitors of human cyclophilin A: virtual screening, synthesis, and bioassay. Bioorganic & Medicinal Chemistry. 2006, 14, 2209-2224. IF: 2.881.
37) Li J., Chen J., Zhang L., Wang F., Gui C., Zhang L., Qin Y., Xu Q., Liu H., Nan F., Shen J., Bai D., Chen K., Shen X.*, Jiang H*. One novel quinoxaline derivative a s a potent human cyclophilin A inhibitor shows highly inhibitory activity against mouse spleen cell proliferation. Bioorganic & Medicinal Chemistry. 2006;14, 5527-5534. IF: 2.881.
38) Daozhen Chen, Huixin Yu, JinDong Bao, Wenqun Xue, Yuan Xing, Li Zhang, William L. Green, Delbert A. Fisher, Sing-Yung Wu. 3, 3’-Diiodothyronine Sulfate Cross-reactive Material (Compound W) in Human Newborns. Pediatric Research. 72, 521-524. IF: 3.123.