科学研究
华国强
 

华国强课题组介绍:

复旦大学放射医学研究所青年研究员,2008年毕业于中国科学院生物物理研究所博士,2009-2014年美国纪念斯隆凯特琳癌症研究所(Memorial Sloan Kettering Cancer Center)博士后从事干细胞类器官和干细胞辐射损伤再生研究。2014年受聘复旦大学放射医学研究所,组建干细胞与再生医学实验室。中华医学会放射医学与防护学青年委员会委员。先后在国际知名杂志Cancer ResearchGastroenterologyNature JCIJ ImmunologyJBCImmunity上发表研究工作,得到国际同行的高度评价。

  

课题组重点:

肠道损伤再生和肠癌发病机制研究

1)肠癌类器官为基础的个性化精准治疗;

2)类器官为基础的高通量再生药物筛选;

3)肠道干细胞在肠道上皮损伤再生修复中的作用。

课题组目前研究的重点是癌症病人的个性化精准治疗和组织再生修复。与传统研究手段不同,课题组依托于最新的3D组织类器官(organoid)培养技术。该组织类器官体系利用病人活检或者手术样品,结合具有3D支撑作用的基质胶和多种细胞生长因子培养形成具有三维立体结构的肠、胃、乳腺、肺、前列腺、肺等正常组织,及肿瘤组织,这种组织块称作类器官(organoid)。类器官因其空间组织结构和细胞成分与正常器官非常相似,从而有助于研究人员直接使用病人的组织进行有针对性的个性化靶向治疗,也可以用作疾病模型或者药物筛选平台。在此基础上,我们将为每一个肿瘤病人建立属于自己的组织类器官,包括正常组织类器官和肿瘤类器官,并在此基础进行多种肿瘤药物和放疗剂量的筛查,建立每一个病人的化疗和放疗敏感性档案,为肿瘤精准的个性化治疗提供数据支撑。

基金支持:

国家自然科学基金面上项目(2015-2018),批准号:31470826

国家自然科学基金面上项目(2017-2020),批准号:31670858


发表论文:

1. Hua, Guoqiang#Wang, ChuPan, YanZeng, ZhaoshiLee, Sang GyuMartin, Maria LauraHaimovitz-Friedman, AdrianaFuks, ZviPaty, Philip BKolesnick, Richard N# Distinct levels of radioresistance in Lgr5+ colonic epithelial stem cells versus Lgr5+ small intestinal stem cells., Cancer Res. 2017 Apr 15; 77(8): 2124-2133. # 共通讯作者)

2. Hua Guoqiang, Thin TH, Feldman R, Haimovitz-Friedman A, Clevers H, Fuks Z, Kolesnick R. Crypt Base Columnar Stem Cells in Small Intestines of Mice Are Radioresistant. Gastroenterology. 2012; 143: 1266-1276.

Highlighted by Gastroenterology, Fixing the Breaks in Intestinal Stem Cells After Radiation: A Matter of DNA Damage and Death or DNA Repair and Regeneration Gastroenterology. 2012: 1144-1147.

3. Lindemans CA, Calafiore M, Mertelsmann AM, O'Connor MH, Dudakov JA, Jenq RR, Velardi E, Young LF, Smith OM, Lawrence G, Ivanov JA, Fu YY, Takashima S, Hua G, Martin ML, O'Rourke KP, Lo YH, Mokry M, Romera-Hernandez M, Cupedo T, Dow LE, Nieuwenhuis EE, Shroyer NF, Liu C, Kolesnick R, van den Brink MR, Hanash AM, Interleukin-22 promotes intestinal stem cell-mediated epithelial regeneration, Nature. 2015 Dec 24; 528(7583): 560-4

4. Hanash AM, Dudakov JA, Hua Guoqiang, et al. Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease. Immunity. 2012 Aug 24; 37(2): 339-50.

Rotolo J, Stancevic B, Zhang J, Hua Guoqiang, Fuller J, Yin X, Haimovitz-Friedman A, Kim K, Qian M, Cardó-Vila M, Fuks Z, Pasqualini R, Arap W, Kolesnick R. Anti-ceramide antibody prevents the radiation gastrointestinal syndrome in mice. J Clin Invest. 2012 May 1; 122(5): 1786-9.

5. Guoqiang Hua, Qixiang Zhang, and Zusen Fan. Heat Shock Protein 75 (TRAP1) Antagonizes Reactive Oxygen Species Generation and Protects Cells from Granzyme M-mediated Apoptosis. J. Biol. Chem., Jul 2007; 282: 20553-20560.

6. Guoqiang Hua, Wang S, Zhong C, Xue P, Fan Z; Ignition of p53 bomb sensitizes tumor cells to granzyme K-mediated cytolysis. J Immunol. 2009 Feb 15; 182(4): 2152-9.

7. Lianfeng Wu, Wang L, Guoqiang Hua, Liu K, Yang X, Zhai Y, Bartlam M, Sun F, Fan Z; Structural basis for proteolytic specificity of the human apoptosis-inducing granzyme M. J Immunol. 2009 Jul 1;183(1):421-9.

8. Tongbiao Zhao, Honglian Zhang, Yuming Guo, Qixiang Zhang, Guoqiang Hua, Hongxia Lu, Qiang Hou, Haiping Liu, and Zusen Fan. Granzyme K cleaves the nucleosome assembly protein SET to induce single-stranded DNA nicks of target cells. Cell Death Differ, Mar 2007; 14(3): 489-99.

9. Jianling Jin, Guoqiang Hua, Chao Bo, et al. The influence of bacterial physiological state on the antibacterial effect of Chinese herbal medicines. Chinese Journal of Traditional and Western Medicine, Jul 2004., 5 (13).

10. Jianling Jin, Yongna Luan, Guoqiang Hua, Peiji Gao. Relation between the antibacterial activity of some herbal drugs and their berberine amount. Acta Chinese Medicine and Pharmacology, Aug 2004., 33 (5): 19-21.

11. 李远闯#, 富国祥, 潘梦雪, 郭强, 饶欣欣, 徐小雅, 周轶, 高建军, 华国强*; 小鼠肠腺瘤类器官培养及其辐射敏感性研究; 复旦学报医学版, 2019.1 (46);

12. Li-Xia Du#, Yan-Qing Wang, Guo-Qiang Hua, Wen-Li Mi*, IL-33/ST2; Pathway as a Rational Therapeutic Target for CNS Diseases, Neuroscience, 2018 (369): 222;

13. 王楚#; 高建军; 华国强*, 肠道类器官在精准医学中的应用, 中国科学: 生命科学, 2017.3.3, 47 (2): 171-179;

14. 富国祥#, 李远闯, 潘梦雪, 郭强, 饶欣欣, 徐小雅, 周轶, 邵春林, 高建军, 华国强*; 利用肠道类器官培养研究表皮调节素的抗辐射作用; 中华放射医学与防护杂志2018 (38): 9.


编写专著

Hua Guoqiang, Kolesnick R. Using ASMase knockout mice to model human diseases. Sphingolipids in Diseases. 2013; (216): 29-54, Springer.


授权专利:

1. 小鼠结直肠X射线照射装置,华国强,富国祥,李远闯,王楚;中国专利,授权,专利号:201621093074.5

2. SIRT1 抑制剂在预防和治疗放射引起的肠道疾病中的应用,华国强,富国祥;中国专利,专利号:201710595602.x

  

实验室图片


验室人员


  

正常类器官                                  肿瘤类器官