A Comparison of the Retinal Microglial Cell Response to Injury in Mice and Zebraf

小鼠和斑马视网膜小胶质细胞对损伤反应的比较

• 批准号: 8568365
• 负责人: ALEX YUAN
• 金额: $ 20.31万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8568365
• 关键词: Address; Animals; Architecture; Award; Cardiac Myocytes; Cell Culture System; Cell Proliferation; Cell Therapy; Cells; Cicatrix; Clinic; Commit; Core Facility; Cultured Cells; Development; Doctor of Medicine; Doctor of Philosophy; Effector Cell; Environment; Equipment; Eye; Fellowship; Fishes; Fluorescence-Activated Cell Sorting; Foundations; Funding; Future; Glial Fibrillary Acidic Protein; Goals; Grant; Green Fluorescent Proteins; Human; Human Resources; Inflammatory; Injury; Institutes; Investigational Therapies; Label; Laboratories; Laboratory Research; Laser injury; Lasers; Lead; Mammals; Mediating; Mentors; Microglia; Mitotic Checkpoint; Modeling; Molecular; Mus; Mutant Strains Mice; Natural regeneration; Organism; Patients; Pattern; Phenotype; Phosphotransferases; Positioning Attribute; Process; Proteins; Recruitment Activity; Regenerative Medicine; Reporter Genes; Research; Research Personnel; Resource Sharing; Retina; Retinal; Retinal Degeneration; Role; Scientist; Secure; Site; Spatial Distribution; Temperature; Testing; Therapeutic; Time; Tissues; Transplantation; Universities; Visual impairment; Washington; Wood material; Work; Zebrafish; base; career; career development; in vitro Model; in vitro activity; in vivo; interest; macrophage; medical schools; meetings; migration; monocyte; mutant; novel; ocular angiogenesis; public health relevance; regenerative; regenerative therapy; response; response to injury; retinal damage; retinal regeneration; teleost fish; temperature sensitive mutant

Project Summary/Abstract I am committed to a career as a clinician scientist and this K08 award will help me realize this goal. My immediate career goal is to establish my own research laboratory. My long term career goal is to develop into a leader in the fields of regenerative medicine and cell based therapies. I graduated with an M.D., Ph.D. from Washington University School of Medicine and completed a postdoctoral research fellowship with Debora Farber, Ph.D. at UCLA. Currently, I hold an associate staff position at the Cole Eye Institute, Cleveland Clinic Foundation. In order to establish my laboratory, I currently see patients 25% of the time and conduct bench research 75% of the time. This award will allow me to maintain this ratio as I develop into an independent investigator and secure funding from an R01. My mentor and co-mentor for this proposal are Bela Anand-Apte, M.B.B.S, Ph.D. and Brian Perkins, Ph.D. Bela is a leader in the field of ocular angiogenesis and Brian is a leader in the field of retinal degenerations and is a zebrafish biologist. I enjoy a collaborative environment with access to shared resources, personnel, and equipment as well as core facilities. They will closely supervise my progress and hold monthly meetings with me to discuss my career development and project progress. I will also meet quarterly with a career development advisory board consisting of my mentor, co-mentor, Dr. Joe Hollyfield, Dr. Neal Peachey, and Dr. John Crabb. I will also take intensive enrichment courses over the summer at Woods Hole and Cold Spring Harbor and courses at Case Western Reserve University School of Medicine. I am interested in looking at the role of scar formation and its effects on retinal regeneration. My hypothesis is the scar is inhibitory to regeneration in the retina. To test this hypothesis, I will investigate scar formation in mice and zebrafish. Mice and other mammals form scars in response to retinal injury. In contrast, zebrafish respond to retinal injury with a robust regenerative response. Microglial cells are surveyors of the retinal environment and they are believed to initiate the scar forming response in mammals. In this proposal we will compare the microglial cell response to a laser induced model of retinal injury in mice and zebrafish. Our specific aims are to (1) define the resident microglia response to injury in both organisms, (2) identify secreted factors which stimulate scar formation in an in vitro model, and (3) determine if inducing scar formation in zebrafish will inhibit retinal regeneration. This grant will allow us to better understand the different injury responses between these two species and will yield important information for future regenerative therapies in humans.

项目总结/摘要 我致力于临床科学家的职业生涯，这个K 08奖将帮助我实现这一目标。我 近期的职业目标是建立自己的研究实验室。我的长期职业目标是发展成为 再生医学和细胞疗法领域的领导者。我是医学博士毕业的博士从 华盛顿大学医学院，并完成了博士后研究奖学金与德博拉 法伯博士在加州大学洛杉矶分校目前，我在克利夫兰诊所的科尔眼科研究所担任助理工作人员 基金会为了建立我的实验室，我目前25%的时间都在看病人， 研究75%的时间。这个奖项将使我保持这个比例，因为我发展成为一个独立的 调查员并从R 01获得资金。 我的导师和这个建议的共同导师是Bela Anand-Apte，M.B.B.S，Ph.D.和布莱恩·帕金斯博士 Bela是眼部血管生成领域的领导者，Brian是视网膜变性领域的领导者， 是一位斑马鱼生物学家我喜欢一个协作的环境，可以访问共享的资源，人员， 设备和核心设施。他们将密切监督我的进展，并每月与我的同事举行会议。 讨论我的职业发展和项目进展。我也会每季度与一个职业 发展顾问委员会由我的导师，共同导师，博士乔Hollyfield，博士Neal Alberhey，博士。 约翰·克拉布我还将在夏天参加伍兹霍尔和冷泉的强化课程 凯斯西储大学医学院的港口和课程。 我感兴趣的是研究瘢痕形成的作用及其对视网膜再生的影响。我的假设是 疤痕抑制视网膜的再生。为了验证这一假设，我将研究瘢痕形成， 老鼠和斑马鱼。老鼠和其他哺乳动物在视网膜损伤后会形成疤痕。相反，斑马鱼 对视网膜损伤做出强有力的再生反应。小胶质细胞是视网膜神经元的监视者。 环境中，并且它们被认为在哺乳动物中引发瘢痕形成反应。在本提案中，我们将 比较小胶质细胞对激光诱导的小鼠和斑马鱼视网膜损伤模型的反应。我们 具体目标是（1）确定两种生物体中固有的小胶质细胞对损伤的反应，（2）鉴定 在体外模型中刺激瘢痕形成的分泌因子，和（3）确定是否诱导瘢痕形成 在斑马鱼中的形成将抑制视网膜再生。这笔赠款将使我们能够更好地了解 这两个物种之间不同的伤害反应，将为未来提供重要信息 人类的再生疗法