The Role of zbtb46 in Endothelial Cell Activation

zbtb46 在内皮细胞激活中的作用

基本信息

批准号：
8891847
负责人：
Amir Rezvan
金额：
$ 12.7万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-05 至 2020-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8891847
关键词：
Affect American Animal Model Antigens ApoE knockout mouse Apolipoprotein E Area Arteries Atherosclerosis Award Basic Science Binding Biology Blood Vessels Cardiology Cardiovascular Diseases Cell Proliferation Cells Cellular biology Cessation of life Chest Pain Computer Simulation Cone Coronary heart disease Data Dendritic Cells Devices Diet Down-Regulation Educational process of instructing Endothelial Cells Endothelium Epigenetic Process Fatty acid glycerol esters Fellowship Program Funding Future Gene Expression Gene Expression Profile Gene Targeting Genes Goals Heart failure ICAM1 gene Immune Immune system Immunology In Vitro Inflammatory Internal Medicine Iran Knock-out Knockout Mice Lead Leukocytes Licensing Ligation Mediating Medical Mentors Messenger RNA MicroRNAs Migration Assay Modeling Morbidity - disease rate Mus Myocardial Infarction NR4A1 gene Nuclear PDGF Signaling Pathway Pathway Analysis Pathway interactions Philadelphia Physicians Play Principal Investigator Process Proteins Publishing RNA Regulation Relaxation Research Research Personnel Residencies Role Science Scientist Signal Transduction Small Interfering RNA Stimulus Stroke System Techniques Testing Time Training Transcription Repressor/Corepressor United States Universities Untranslated Regions Up-Regulation atheroprotective base clinical practice endothelial dysfunction feeding immune activation in vivo inhibitor/antagonist insight interest mortality mouse model novel overexpression prevent professor public health relevance response shear stress statistics targeted treatment therapeutic target vascular inflammation

项目摘要

DESCRIPTION (provided by applicant): The goal of this K08 mentored award is to provide funding for developing the principal investigator (PI) into an independent physician-scientist in the field of cardiovascular disease. The PI, Dr. Amir Rezvan, obtained his MD degree from Iran University of Medical Sciences, followed by an MS degree in Biomedical Science from Drexel University in Philadelphia, where he studied the effects of shear stress on the endothelium. He then completed his Internal Medicine residency at Drexel University and moved to Atlanta to continue his training in Cardiovascular Disease in a four year basic science research track fellowship program at Emory University. He then joined the Division of Cardiology at Emory University as an Assistant Professor. He is currently a licensed physician in the State of Georgia and is certified by the American Board of Internal Medicine in both Internal Medicine and Cardiovascular Disease. He will be allocating 75% of his time to research proposed in this application and 25% of his time to practicing clinical cardiology and teaching residents and fellows in the university setting. This project will focus on the role of shear stress regulated ZBTB46 expression in endothelial cells (ECs) on EC activation. The PI will test the hypothesis that ZBTB46, a transcription repressor responsible for preventing immune activation in dendritic cells, is expressed under laminar shear conditions in ECs and is downregulated by disturbed flow, leading to activation of ECs. The PI will then test the role of shear sensitive miRs with potential targeting of ZBTB46 on its down-regulation by disturbed flow. He will then test the hypothesis that alterations in ZBTB46 levels in ECs (by down-regulating or overexpressing) will alter EC gene expression, specifically potential target genes for ZBTB46 such as NR4A1(NFkB inhibitor), PDGFC, and NFkB mediated genes such as VCAM1 and ICAM1 as well as affecting EC proliferation and tubule formation. Lastly, the PI will test the hypothesis that knockdown of ZBTB46 in an animal model leads to increased endothelial dysfunction and atherosclerosis. Dr. Rezvan will benefit from a team of mentors including Dr. Hanjoong Jo, an established investigator and expert in vascular biology, Dr. W. Robert Taylor, a physician-scientist and expert in vascular inflammation, Dr. Arash Grakoui, an established investigator in the field of immunology, and Dr. Jeremy Boss, an established investigator and expert in gene expression and epigenetics. This group of mentors will provide additional expertise and training needed for the PI to reach his short term goal of achieving scientific independence while furthering the understanding of role of ZBTB46 in EC activation, leading to his long term goal of becoming an established physician-scientist and succeeding in developing novel therapies to prevent and treat atherosclerotic disease while mentoring younger physicians and scientists.

描述（由适用提供）：该K08指导奖的目的是为将主要研究者（PI）提供资金，成为心血管疾病领域的独立身体科学家。 PI Amir Rezvan博士从伊朗医学科学大学获得了医学博士学位，随后是费城德雷克塞尔大学的生物医学科学硕士学位，在那里他研究了剪切压力对内皮的影响。然后，他在德雷克塞尔大学（Drexel University）完成了内科住所，并搬到亚特兰大（Atlanta）继续在埃默里大学（Emory University）的四年基础科学研究奖学金计划中继续接受心血管疾病的培训。然后，他加入埃默里大学的心脏病学系，担任助理教授。他目前是佐治亚州有执照的身体，并获得了美国内科和心血管疾病的美国内科委员会的认证。他将分配75％的时间来进行此应用程序提出的研究，并在大学环境中练习临床心脏病学以及教授居民和研究员的时间的25％。该项目将重点介绍剪切应力调节的ZBTB46在内皮细胞（ECS）在EC激活中的作用。 PI将检验以下假设：ZBTB46是负责预防树突状细胞免疫激活的转录代表，在ECS的层状剪切条件下表达，并因流动而下调，导致EC激活。然后，PI将测试剪切敏感的miR的作用，而ZBTB46的潜在靶向其通过干扰流动的下调。然后，他将检验以下假设：EC中ZBTB46水平的变化（通过下调或过表达）将改变EC基因的表达，特别是ZBTB46的潜在靶基因，例如NR4A1（NFKB抑制剂），PDGFC，PDGFC和NFKB介导的GENES和ICAM1和ICAM1和ICAM1和ICAM1和ICAM1和ICAM1和ICAM1和ICAM1和ICAM1和ICAM1和ICAM1和ICAM1和ICAM1和ICAM1和ICAM1及其影响。最后，PI将检验以下假设：动物模型中ZBTB46的敲低导致内皮功能障碍和动脉粥样硬化增加。 Rezvan博士将受益于一组导师，包括Hanjoong Jo博士，汉乔恩·乔（Hanjoong Jo）博士，他是血管生物学的研究员兼专家W. Robert Taylor博士，W。RobertTaylor博士，身体科学家和血管感染的专家Arash Grakoui博士，一名免疫学领域的研究员Arash Grakoui博士，杰里米（Jeremy）的研究员，杰里米（Jeremy）的老板博士，固定的研究员和专家的表达和专家Eppement和Eppegenics。这组导师将为PI提供更多的专业知识和培训，以实现他实现科学独立性的短期目标，同时进一步了解ZBTB46在EC激活中的作用，从而导致他的长期目标是成为既定的医生 - 科学家，并成为一种既定的医生 - 科学家，并成功地开发新颖的疗法，以预防和治疗动态疾病，同时使动物疾病的年轻物理学家和科学家进行心理训练。