基因编辑学术研讨会 -2018年3月30-31日北京

广州市妇女儿童医疗中心

朱洁，眼科学博士，美国加州大学圣地亚哥分校Shiley眼科研究所博士后，2017年3月回国后在广州市妇女儿童医疗中心眼科工作。长期致力于眼科重大疾病的临床及应用基础研究，在白内障、视网膜色素变性、眼内新生血管性疾病、青光眼及眼部肿瘤等的病因和发病机制、治疗靶点和干预手段的等方面取得了一系列重要的研究成果。其中对于CRISPR/Cas9细胞编程技术治疗眼部遗传变性疾病、晶体干细胞原位动员再生功能性晶状体治疗先天性白内障、蛋白质积聚与白内障形成、结合3D打印的角膜缘干细胞移植技术治疗眼表疾病、视网膜干细胞在青光眼视神经损伤防治中的应用等均有较为深入的研究。相关研究成果以第一作者和合作作者在Nature、Cell Research、Cancer Cell、Molecular Cell、PNAS及Biomaterials等国际知名期刊上发表SCI收录文章25篇，总影响因子329分，累计被引用1000余次，承担和参与国家重点基础研究发展计划（973计划）、国家自然科学基金等多项研究项目，得到了国际同行的广泛关注和高度肯定。

演讲报告题目摘要：

CRISPR-Cas9介导的光感受器细胞重编程治疗视网膜色素变性
基因治疗已经在多种人类疾病治疗中显示出巨大的潜能。然而目前的方法通常只针对单个基因或单个突变，使得对多基因或多点突变的疾病治疗受到极大限制。视网膜色素变性是临床常见的致盲眼病，极具临床和遗传异质性，是导致人类视力障碍最主要的疾病之一。目前已有超过40个基因和位点被报道与视网膜色素变性有关。这里我们采用CRISPR/Cas9介导的基因编辑方法，对视网膜色素变性小鼠进行了基因治疗。通过突变视杆细胞中重要的转录因子Nrl或Nr2e3，将视杆细胞重编程为视锥细胞。转化后的视锥样细胞对突变引起的感光细胞退化不敏感，从而使小鼠在发病后期仍能保留一定程度的视力。我们的发现不仅为视网膜色素变性提供了新的不依赖于基因突变的治疗方法，而且证明了基因编辑技术介导的细胞重编程、细胞退化预防以及组织功能保护的巨大可能性。

研究方向：

干细胞分化调控及在眼部疾病防治中的应用
CRISPR/Cas9细胞编程技术在眼部遗传变性疾病中的应用
青光眼视神经损伤及保护
眼内新生血管的发生与调控
细胞与细胞外基质的相互作用及信号转导
3D打印及组织工程

学习和工作经历：

2005.08-2008.06，第四军医大学眼科学博士
2014.02-2017-03，美国加州大学圣地亚哥分校Shiley眼科研究所博士后

近期发表论文：

1. Xu RH, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, Yi S, Shi W, Quan Q, Li K, Zheng L, Zhang H, Caughey BA, Zhao Q, Hou J, Zhang R, Xu Y, Cai H, Li G, Hou R, Zhong Z, Lin D, Fu X, Zhu J, Duan Y, Yu M, Ying B, Zhang W, Wang J, Zhang E, Zhang C, Li O, Guo R, Carter H, Zhu JK, Hao X, Zhang K. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat Mater. 2017 Nov;16(11):1155-1161. (IF 39.736)

2. Hao X, Luo H, Krawczyk M, Wei W, Wang W, Wang J, Flagg K, Hou J, Zhang H, Yi S, Jafari M, Lin D, Chung C, Caughey BA, Li G, Dhar D, Shi W, Zheng L, Hou R, Zhu J, Zhao L, Fu X, Zhang E, Zhang C, Zhu JK, Karin M, Xu RH, Zhang K. DNA methylation markers for diagnosis and prognosis of common cancers. Proc Natl Acad Sci U S A. 2017 Jul 11;114(28):7414-7419. (IF 9.661)

3. Zhu J*, Ming C*, Fu X*, Duan Y, Hoang DA, Rutgard J, Zhang R, Wang W, Hou R, Zhang D, Zhang E, Zhang C, Hao X, Xiong W, Zhang K. Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors. Cell Res. 2017 Jun;27(6):830-833. (IF 15.606)

4. Zhu W*, Qu X*, Zhu J, Ma X, Patel S, Liu J, Wang P, Lai CS, Gou M, Xu Y, Zhang K, Chen S. Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture. Biomaterials. 2017 Feb 2;124:106-115. (IF 8.387)

5. Suzuki K*, Tsunekawa Y*, Hernandez-Benitez R*, Wu J*, Zhu J, Kim EJ, Hatanaka F, Yamamoto M, Araoka T, Li Z, Kurita M, Hishida T, Li M, Aizawa E, Guo S, Chen S, Goebl A, Soligalla RD, Qu J, Jiang T, Fu X, Jafari M, Esteban CR, Berggren WT, Lajara J, Nuñez-Delicado E, Guillen P, Campistol JM, Matsuzaki F, Liu GH, Magistretti P, Zhang K, Callaway EM, Zhang K, Belmonte JC. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration. Nature. 2016 Dec 1;540(7631):144-149. (IF 40.137)

6. Wang WQ, Wang FH, Qin WX, Liu HY, Lu B, Chung C, Zhu J, Gu Q, Shi W, Wen C, Wu F, Zhang K, Sun XD. Joint Antiangiogenic Effect of ATN-161 and Anti-VEGF Antibody in a Rat Model of Early Wet Age-Related Macular Degeneration. Mol Pharm. Accepted. PMID: 27089240. (IF 4.342)

7. Yoo JH, Shi DS, Grossmann AH, Sorensen LK, Tong Z, Mleynek TM, Rogers A, Zhu W, Richards JR, Winter JM, Zhu J, Dunn C, Bajji A, Shenderovich M, Mueller AL, Woodman SE, Harbour JW, Thomas KR, Odelberg SJ, Ostanin K, Li DY. ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma. Cancer Cell. 2016 Jun 13;29(6):889-904. (IF 27.407)

8. Lin H*, Ouyang H*, Zhu J*, Huang S*, Liu Z, Chen S, Cao G, Li G, Signer R, Xu Y, Chung C, Zhang Y, Lin D, Patel S, Wu F, Cai H, Hou J, Wen C, Jafari M, Liu X, Luo L, Zhu J, Qiu A, Hou R, Chen B, Chen J, Granet D, Heichel C, Shang F, Li X, Krawczyk M, Skowronska-Krawczyk D, Wang Y, Shi W, Chen D, Zhong Z, Zhong S, Zhang L, Chen S, Morrison S, Maas R, Zhang K, Liu Y. Lens regeneration using endogenous stem cells with gain of visual function. Nature. 2016 Mar 17; 531 (7594): 323-8. (*Co-first Author) (IF 40.137)

9. Hodgson N, Wu F, Ferreyra H, Zhu J, Wang W, Zhang K, Wang J. Economic and Quality of Life Benefits of Anti-VEGF Therapy. Mol Pharm. 2016 Feb 2. [Epub ahead of print] PubMed PMID: 26836112. (IF 4.384)

10. Wu F, Wang S, Zhu J, Rutgard J, Yan YB, Zhang K, Zhao L. Public impact, prevention, and treatment of cataracts. Sci China Life Sci. 2015 Nov;58(11):1157-9. (IF 1.688)

11. Hu CJ, Fang RH, Wang KC, Luk BT, Thamphiwatana S, Dehaini D, Nguyen P, Angsantikul P, Wen CH, Kroll AV, Carpenter C, Ramesh M, Qu V, Patel SH, Zhu J, Shi W, Hofman FM, Chen TC, Gao W, Zhang K, Chien S, Zhang L. Nanoparticle biointerfacing by platelet membrane cloaking. Nature. 2015 Sep 16. doi: 10.1038/nature15373. (IF 40.137)

12. Skowronska-Krawczyk D, Zhao L, Zhu J, Weinreb RN, Cao G, Luo J, Flagg K, Patel S, Wen C, Krupa M, Luo H, Ouyang H, Lin D, Wang W, Li G, Xu Y, Li O, Chung C, Yeh E, Jafari M, Ai M, Zhong Z, Shi W, Zheng L, Krawczyk M, Chen D, Shi C, Zin C, Zhu J, Mellon PL, Gao W, Abagyan R, Zhang L, Sun X, Zhong S, Zhuo Y, Rosenfeld MG, Liu Y, Zhang K. P16INK4a Upregulation Mediated by SIX6 Defines Retinal Ganglion Cell Pathogenesis in Glaucoma. Mol Cell. 2015 Sep 17;59(6):931-40. (IF 14.018)

13. Zhao L*, Chen XJ*, Zhu J*, Xi YB*, Yang X, * Hu LD*, Ouyang H, Patel SH, Jin X, Lin D, Wu F, Flagg K, Cai H, Li G, Cao G, Lin Y, Chen D, Wen C, Chung C, Wang Y, Qiu A, Yeh E, Wang W, Hu X, Grob S, Abagyan R, Su Z, Tjondro HC, Zhao XJ, Luo H, Hou R, Perry JJ, Gao W, Kozak I, Granet D, Li Y, Sun X, Wang J, Zhang L, Liu Y, Yan YB, Zhang K. Lanosterol reverses protein aggregation in cataracts. Nature. 2015 Jul 30;523(7562):607-11. (*Co-first Author) (IF 40.137)

14. Li G, Xu F, Zhu J, Krawczyk M, Zhang Y, Yuan J, Patel S, Wang Y, Lin Y, Zhang M, Cai H, Chen D, Zhang M, Cao G, Yeh E, Lin D, Su Q, Li WW, Sen GL, Afshari N, Chen S, Maas RL, Fu XD, Zhang K, Liu Y, Ouyang H. Transcription Factor PAX6 (Paired Box 6) Controls Limbal Stem Cell Lineage in Development and Disease. J Biol Chem. 2015 Aug 14;290(33):20448-54. (IF 4.573)

15. Shi K, Wang X, Zhu J, Cao G, Zhang K, Su Z. Salidroside protects retinal endothelial cells against hydrogen peroxide-induced injury via modulating oxidative status and apoptosis. Biosci Biotechnol Biochem. 2015;79(9):1406-13. (IF 1.063)

16. Huu VA, Luo J, Zhu J, Zhu J, Patel S, Boone A, Mahmoud E, McFearin C, Olejniczak J, de Gracia Lux C, Lux J, Fomina N, Huynh M, Zhang K, Almutairi A. Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye. J Control Release. 2015; 200C: 71-77. (IF 7.261)

17. Zhu T*, Zhu J*, Bu X*, Zhao H, Zhang SY, Chang Y, Li R, Yao LB, Wang YS, Su J. The anti-angiogenic role of discoidin domain receptor 2 (DDR2) in laser-induced choroidal neovascularization. J Mol Med (Berl). 2015; 93(2): 187-98. (*Co-first Author) (IF 4.739)

18. Chi W, Li F, Chen H, Wang Y, Zhu Y, Yang X, Zhu J, Wu F, Ouyang H, Ge J, Weinreb RN, Zhang K, Zhuo Y. Caspase-8 promotes NLRP1/NLRP3 inflammasome activation and IL-1β production in acute glaucoma. Proc Natl Acad Sci USA. 2014; 111: 11181-11186. (IF 9.809)