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: 8708880
• 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/8708880
• 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

DESCRIPTION (provided by applicant): 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 environmen 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.

描述（由申请人提供）：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来自华盛顿大学医学院，并与Debora Farber博士一起完成了博士后研究。在加州大学洛杉矶分校目前，我在克利夫兰诊所基金会的科尔眼科研究所担任助理工作人员。为了建立我的实验室，我目前有25%的时间看病人，75%的时间进行实验室研究。这个奖项将使我能够保持这个比例，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，是斑马鱼生物学家。我喜欢一个协作的企业家，可以共享资源，人员和设备以及核心设施。他们将密切监督我的进展，并每月与我举行会议，讨论我的职业发展和项目进展。我还将每季度与职业发展顾问委员会会面，该委员会由我的导师、共同导师、乔·霍利菲尔德博士、尼尔·霍利菲尔德博士和约翰·克拉布博士组成。我还将在夏天参加伍兹霍尔和冷泉港的强化课程，以及凯斯西储大学医学院的课程。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了视网膜的再生。为了验证这个假设，我将 研究小鼠和斑马鱼瘢痕形成。老鼠和其他哺乳动物在视网膜损伤后会形成疤痕。相比之下，斑马鱼对视网膜损伤的反应是强烈的再生反应。小胶质细胞是视网膜环境的监视者，并且它们被认为在哺乳动物中启动瘢痕形成反应。在这个提议中，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。我们的具体目标是（1）确定两种生物体中小胶质细胞对损伤的反应，（2）在体外模型中鉴定刺激瘢痕形成的分泌因子，（3）确定 在斑马鱼中诱导瘢痕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的不同损伤反应，并将为人类未来的再生治疗提供重要信息。