團(tuán)隊(duì)人員

1.  研究組長：金子兵教授，金老師同時(shí)兼任溫州醫(yī)科大學(xué)研究生院院長。金老師曾在日本留學(xué)和工作了8年多，在日本理化學(xué)研究所先后做博士后和特聘研究員，日本理化學(xué)研究所相當(dāng)于我國中科院的研究機(jī)構(gòu)。2012年發(fā)現(xiàn)iPS制備方法的諾貝爾獎(jiǎng)獲得者就是在這個(gè)研究所工作，金老師在日本也是從事干細(xì)胞方面的研究。金老師于2011年回國，組建自己的實(shí)驗(yàn)室。一直與日本的理化學(xué)研究所的科學(xué)家，高橋政代保持密切的合作，高橋教授是全球首位用iPS細(xì)胞進(jìn)行臨床試驗(yàn)的科學(xué)獎(jiǎng)，2014被Nature評(píng)為全球十大杰出科學(xué)家。所以我們實(shí)驗(yàn)室是中日聯(lián)合視網(wǎng)膜再生醫(yī)療實(shí)驗(yàn)室。在學(xué)校領(lǐng)導(dǎo)的支持下，2015年溫州醫(yī)科大學(xué)干細(xì)胞研究所正式掛牌成立，金老師任研究所的所長。

2.  工作人員：潘少輝、高美玲、陳雪姣、潘登、孫蘭芳、劉慧、林強(qiáng)、黃秀峰、呂技能、項(xiàng)略、徐小濤、毛建洋

研究方向：

本團(tuán)隊(duì)的研究主要關(guān)注視網(wǎng)膜變性疾病，這是一種神經(jīng)退行性疾病，在全球引起眾多病人的不可逆的視力損傷以及失明。代表性的視網(wǎng)膜變性疾病包括遺傳性視網(wǎng)膜營養(yǎng)不良(IRD)、年齡相關(guān)性黃斑變性和糖尿病性視網(wǎng)膜病變。我們致力于闡明RP的疾病機(jī)制，轉(zhuǎn)化實(shí)驗(yàn)室技術(shù)以改善臨床治療，并與視網(wǎng)膜專家共同解決關(guān)鍵的基本問題。我們實(shí)驗(yàn)室的主要技術(shù)包括臨床遺傳學(xué)和新的捕獲測(cè)序、分子生物學(xué)、多能干細(xì)胞和分化，以及實(shí)驗(yàn)動(dòng)物模型（小鼠和獼猴）。

遺傳性視網(wǎng)膜營養(yǎng)不良(IRD)，包括視網(wǎng)膜色素變性（RP）、Stargardt病、錐體營養(yǎng)不良或錐形桿營養(yǎng)不良等一系列單基因視力減退性疾病。常見的表現(xiàn)是視桿細(xì)胞和/或視錐細(xì)胞的病理變化，視網(wǎng)膜中的特化和光敏神經(jīng)元。目前，超過165種致病基因與IRD相關(guān)，顯示出疾病的極端遺傳異質(zhì)性，因此使分子診斷在技術(shù)上具有挑戰(zhàn)性，因?yàn)檫@需要大量的時(shí)間和資源。我們開發(fā)了一種定制的捕獲測(cè)序策略來全面執(zhí)行IRD患者的分子診斷，這將改善臨床診斷和患者預(yù)后，相關(guān)結(jié)果發(fā)表在Genetic in Medicine上。我們最近發(fā)現(xiàn)了常染色體隱性RP的第37個(gè)基因SLC7A14，并闡明了其體內(nèi)和體外的疾病機(jī)制，結(jié)果發(fā)表在Nature Communication上。

年齡相關(guān)性黃斑變性（AMD）是一種與年齡有關(guān)的退化性黃斑病，引起不可避免的視力喪失。中國的流行率在3％左右，而且隨著年齡的增長，應(yīng)該會(huì)大幅增加。過去幾十年來，人們對(duì)了解遺傳因素以及環(huán)境因素，開展抗VEGF治療以解決新生血管相關(guān)并發(fā)癥作出了巨大的努力。就疾病病因而言，視網(wǎng)膜色素上皮（RPE）功能障礙和解體是關(guān)鍵病變。我們正在開發(fā)使用誘導(dǎo)多能干（iPS）細(xì)胞和生物可降解支架的RPE替代療法，相關(guān)結(jié)果發(fā)表在Biomaterials上。

最近，我們首次建立了RP患者來源的體外疾病模型和藥物測(cè)試的iPS細(xì)胞系，結(jié)果發(fā)表在PLoS One，Stem Cells Transl Med 等。為該領(lǐng)域的患者特異性iPS應(yīng)用打開了大門。 我們正在使用這些尖端的，先進(jìn)的工具在實(shí)驗(yàn)室中進(jìn)行疾病機(jī)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.