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视网膜再生医疗研究组

作者:佚名    来源:实验中心    发布时间:2018/1/8 15:12:12    点击量:    【打印文章】

团队人员

1.  研究组长:金子兵教授,金老师同时兼任温州医科大学研究生院院长。金老师曾在日本留学和工作了8年多,在日本理化学研究所先后做博士后和特聘研究员,日本理化学研究所相当于我国中科院的研究机构。2012年发现iPS制备方法的诺贝尔奖获得者就是在这个研究所工作,金老师在日本也是从事干细胞方面的研究。金老师于2011年回国,组建自己的实验室。一直与日本的理化学研究所的科学家,高桥政代保持密切的合作,高桥教授是全球首位用iPS细胞进行临床试验的科学奖,2014被Nature评为全球十大杰出科学家。所以我们实验室是中日联合视网膜再生医疗实验室。在学校领导的支持下,2015年温州医科大学干细胞研究所正式挂牌成立,金老师任研究所的所长。

2.  工作人员:潘少辉、高美玲、陈雪姣、潘登、孙兰芳、刘慧、林强、黄秀峰、吕技能、项略、徐小涛、毛建洋

 

研究方向:

本团队的研究主要关注视网膜变性疾病,这是一种神经退行性疾病,在全球引起众多病人的不可逆的视力损伤以及失明。代表性的视网膜变性疾病包括遗传性视网膜营养不良(IRD)、年龄相关性黄斑变性和糖尿病性视网膜病变。我们致力于阐明RP的疾病机制,转化实验室技术以改善临床治疗,并与视网膜专家共同解决关键的基本问题。我们实验室的主要技术包括临床遗传学和新的捕获测序、分子生物学、多能干细胞和分化,以及实验动物模型(小鼠和猕猴)。

遗传性视网膜营养不良(IRD),包括视网膜色素变性(RP)、Stargardt病、锥体营养不良或锥形杆营养不良等一系列单基因视力减退性疾病。常见的表现是视杆细胞和/或视锥细胞的病理变化,视网膜中的特化和光敏神经元。目前,超过165种致病基因与IRD相关,显示出疾病的极端遗传异质性,因此使分子诊断在技术上具有挑战性,因为这需要大量的时间和资源。我们开发了一种定制的捕获测序策略来全面执行IRD患者的分子诊断,这将改善临床诊断和患者预后,相关结果发表在Genetic in Medicine上。我们最近发现了常染色体隐性RP的第37个基因SLC7A14,并阐明了其体内和体外的疾病机制,结果发表在Nature Communication上。

年龄相关性黄斑变性(AMD)是一种与年龄有关的退化性黄斑病,引起不可避免的视力丧失。中国的流行率在3%左右,而且随着年龄的增长,应该会大幅增加。过去几十年来,人们对了解遗传因素以及环境因素,开展抗VEGF治疗以解决新生血管相关并发症作出了巨大的努力。就疾病病因而言,视网膜色素上皮(RPE)功能障碍和解体是关键病变。我们正在开发使用诱导多能干(iPS)细胞和生物可降解支架的RPE替代疗法,相关结果发表在Biomaterials上。

最近,我们首次建立了RP患者来源的体外疾病模型和药物测试的iPS细胞系,结果发表在PLoS One,Stem Cells Transl Med 等。为该领域的患者特异性iPS应用打开了大门。 我们正在使用这些尖端的,先进的工具在实验室中进行疾病机制研究。

 

the Retinal Regenerative Medical Research Group

Team Members

1.       Principle Investigator: Zi-Bing Jin, M.D. & Ph.D.

Professor Jin is the Dean of the Graduate School of Wenzhou Medical University. Jin has studied and worked in Japan for more than eight years and completed postdoctoral training at REKEN and become a JSPS fellow there. The REKEN of Japan is equivalent to the research institute of Chinese Academy of Sciences. The Nobel winner Yamanaka who discovered the iPS preparation method worked at this institute in 2012, and at the same time Jin also worked on stem cells in Dr. Takahashi’s lab in Japan . Jin returned to China in 2011 to set up his own laboratory. Dr. Takahashi has been the world's first scientific conducted clinical trials with iPS cells. In 2014, Dr. Takahashi was award as the Nature's Top Ten Outstanding Scientists by Nature. Therefore, our laboratory is a Sino-Japanese joint retinal regeneration medical laboratory. The Stem Cell Institute of Wenzhou Medical University was formally established in 2015, and Professor Jin is the director of the institute.

2.       Team Staff: Shaohui Pan, Meiling Gao, Xuejiao Chen, Deng Pan, Lanfang Sun, Hui Liu, Qiang Lin, Xiufeng Huang, Jineng Lu, Lue Xiang, Xiaotang Xu, Jianyang Mao.

 

Scope of Research Proposal

Retinal degeneration (RD) is a group of degenerative diseases occurring in human retina and is the leading cause of inevitable vision loss as well as midway blindness worldwide. The major representative RD includes inherited retinal dystrophy (IRD), age-related macular degeneration (AMD), and diabetic retinopathy (DR). We are dedicating to make efforts on elucidating the disease mechanisms of RP, translating laboratory technology to improve bedside outcome, and solving key basic problems together with retina specialists. The major technologies in our laboratory include clinical genetics and new capture sequencing, molecular biology, pluripotent stem cell & differentiation, experimental animal models (mouse and macaque).

IRD is a group of monogenic, vision-impairing diseases including retinitis pigmentosa (RP), Stargardt's disease, cone dystrophy or cone-rod dystrophy, etc. The common manifestation is a pathological change in rod and/or cone photoreceptor cells, which are the specialized and light-sensitive neurons in the retina. Currently, more than 165 disease-causing genes have been linked to IRD demonstrating the extreme genetic heterogeneity of the disease and therefore making molecular diagnosis technically challenging because it would require a massive commitment of time and resources. We have developed a customized capture sequencing strategy to comprehensively perform molecular diagnosis for IRD patients (PLoS One 2013; Genet Med 2014; Genet Med 2015), which would improve clinical diagnosis and patient outcome. We discovered the 37th gene of autosomal recessive RP, SLC7A14, recently and elucidated its disease mechanism in vitro and in vivo (Nat Commun 2014).

AMD is an age-related degenerative macular disease causing inevitable vision loss. It's prevalence is around 3% in China and supposed to increase significantly with the coming age of ageing. In the past decades, great efforts have been made on understanding genetic predispositions as well as environmental factors, and developing anti-VEGF therapy to solve neovascularization-related complications. In term of the disease etiology, retina pigment epithelium (RPE) dysfunction and disorganization are the key lesions. We are developing RPE replacement therapy using induced pluripotent stem (iPS) cells and bio-degradable scaffolds (Biomaterials 2014).

Recently we for the first time established RP patient-derived iPS cell lines for in vitro disease modeling and drug test (PLoS One 2011; Stem Cells Transl Med 2012), opening the door of patient-specific iPS application in the field. We are keeping on the disease mechanism study using these cutting-edge, state-of-art tools in the laboratory.