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

描述(申请人提供)：我致力于作为一名临床科学家的职业生涯，这个K08奖项将帮助我实现这个目标。我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再生医学和细胞疗法领域的领导者。我毕业于华盛顿大学医学院，获得医学博士学位，并与加州大学洛杉矶分校的博士黛博拉·法伯一起完成了博士后研究。目前，我在克利夫兰临床基金会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%的时间进行长凳研究。这项奖励将使我在发展成为一名独立调查员并从R01获得资金的过程中保持这一比例。我的导师和共同导师是Bela Anand-Apte，M.B.B.S，Ph.D.和Brian Perkins，Ph.D.Bela是眼睛血管生成领域的领导者，Brian是视网膜退化领域的领导者，是斑马鱼生物学家。我喜欢一个协作的环境，可以使用共享的资源、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咨询委员会会面，该委员会由我的导师、共同导师乔·霍利菲尔德博士、尼尔·皮奇博士和约翰·克拉布博士组成。今年夏天，我还将在伍兹霍尔和冷泉港参加强化培训课程，以及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，疤痕对视网膜再生有抑制作用。为了检验这一假设，我将 研究小鼠和斑马鱼的疤痕形成。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的反应是强大的再生反应。小胶质细胞是视网膜环境的监测器，它们被认为启动了哺乳动物的疤痕形成反应。在这项建议中，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)确定两种生物对损伤的常驻小胶质细胞的反应，(2)在体外模型中识别刺激瘢痕形成的分泌因子，以及(3)确定是否 诱导斑马鱼的疤痕形成会抑制视网膜再生。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损伤反应，将为未来的人类再生治疗提供重要信息。

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.