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

项目摘要/摘要 我致力于临床科学家的职业生涯，这个K08奖将帮助我实现这一目标。我的 目前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 在再生医学和细胞疗法领域处于领先地位。我毕业于哈佛大学，拥有医学博士和博士学位 并与黛博拉一起完成了博士后研究 法伯，加州大学洛杉矶分校的博士。目前，我在克利夫兰诊所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，我目前有25%的时间看病人，并进行长凳 75%的时间都在研究。这个奖项将使我在成长为独立的 调查人员，并从R01获得资金。 我这项提案的导师和共同导师是贝拉·阿南德-阿普特，MBA，博士和布莱恩·珀金斯博士。 贝拉是眼血管生成领域的领先者，布莱恩是视网膜退行性变和 是一位斑马鱼生物学家。我喜欢协作环境，可以访问共享的资源、人员和 设备以及核心设施。他们将密切监督我的进度，并每月与 让我来讨论我的职业发展和项目进展。我也会每季度与事业相遇 发展顾问委员会由我的导师、共同导师、乔·霍利菲尔德博士、尼尔·皮奇博士和尼尔·皮奇博士组成。 约翰·克拉布。我还将在伍兹霍尔和冷泉参加暑期强化课程 港口和凯斯西储大学医学院的课程。 我对研究疤痕形成的作用及其对视网膜再生的影响很感兴趣。我的假设是 疤痕对视网膜的再生有抑制作用。为了验证这一假设，我将研究 老鼠和斑马鱼。老鼠和其他哺乳动物对视网膜损伤会形成疤痕。相比之下，斑马鱼 对视网膜损伤有强大的再生反应。小胶质细胞是视网膜的观察者。 它们被认为是启动哺乳动物的疤痕形成反应的因素。在本提案中，我们将 比较小鼠和斑马鱼小胶质细胞对激光诱导的视网膜损伤模型的反应。我们的 具体目标是(1)确定两种生物对损伤的常驻小胶质细胞反应，(2)确定 在体外模型中刺激瘢痕形成的分泌因子，以及(3)决定是否诱导瘢痕形成 斑马鱼体内的形成会抑制视网膜再生。这笔拨款将使我们更好地了解 这两个物种之间的伤害反应不同，这将为未来提供重要信息 人类的再生疗法。

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.