Galectin-3-Mediated Post-Ischemic Myocardial Dysfunction and its Inhibition by a Novel Peptide N-Acetyl-Seryl-Aspartyl-Lysyl-Proline

Galectin-3介导的缺血后心肌功能障碍及其新肽N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸的抑制作用

• 批准号: 10213113
• 负责人: Umesh C Sharma
• 金额: $ 19.74万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10213113
• 关键词: Acute; Address; Animal Experimentation; Animals; Antiinflammatory Effect; Attenuated; Automobile Driving; Award; Biological; Biometry; Buffaloes; Cardiac; Cardiac Myocytes; Cardiac development; Cardiomyopathies; Cardiovascular system; Center for Translational Science Activities; Clinical Research; Continuous Infusion; Cyclin D1; DNA Sequence Alteration; Data; Development Plans; Faculty; Fibrosis; Functional disorder; Funding; Future; Galectin 3; Goals; Heart; Heart Injuries; Heart failure; Image; In Vitro; Infiltration; Inflammation; Inflammatory; Injections; Ischemia; Knockout Mice; Lead; Liposomes; Magnetic Resonance Imaging; Mediating; Mediator of activation protein; Medicine; Mentorship; Modeling; Molecular; Morbidity - disease rate; Mus; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardial dysfunction; Myocardium; Nuclear; Peptides; Peptidyl-Dipeptidase A; Physiology; Plasma; Play; Positioning Attribute; Process; Reporting; Research; Research Design; Research Ethics; Research Personnel; Resources; Role; Route; Structure; System; Technology; Testing; Therapeutic; Therapeutic Effect; Tissue imaging; Training; Universities; Ventricular Remodeling; base; cardiogenesis; career development; clinical translation; coronary fibrosis; design; gain of function; heart function; heart preservation; inhibitor/antagonist; ischemic injury; lysylproline; macrophage; migration; molecular imaging; mortality; mouse model; myocardial injury; new therapeutic target; novel; overexpression; pre-clinical; preservation; prevent; professor; response; skills; therapeutic target; translational study

PROJECT SUMMARY This proposal describes a five-year career development and training plan for Dr. Umesh Sharma under the mentorship of Professor John M. Canty, Jr. Dr. Sharma is currently an Assistant Professor of Medicine at University at Buffalo. His career development plan, that leverages the extensive resources offered by the University and Clinical and Translational Research Center at Buffalo, brings together a strong team of investigators with expertise in small animal physiology, myocardial remodeling, therapeutics and dynamic magnetic resonance imaging. During the period of funding, Dr. Sharma will have a faculty position in the Division of Cardiovascular Medicine at University at Buffalo. His goal is to become a successful and independent investigator studying mechanisms of ischemia-induced myocardial injury and dysfunction, and identify novel therapeutic targets. Receipt of this award will allow Dr. Sharma obtain additional training in small-animal research, comprehensive cardiac tissue and molecular imaging, biostatistics, research design and ethics, and will facilitate his transition to research independence. Dr. Sharma hypothesizes that in presence of ischemic myocardial injury, excess galectin-3 promotes myocardial inflammation and fibrosis. Blocking galectin-3 activity via genetic mutation or therapeutic antagonism inhibits inflammation, reduces fibrosis and preserves cardiac function. Dr. Sharma has a strong research track-record and has obtained excellent preliminary results that show the feasibility of this approach in a murine model of myocardial ischemia. In summary, by bringing together cutting edge technology and a well-rounded team of experts in the setting of excellent research plan and mentorship structure, Dr. Sharma will be able to synergistically merge the fields of advanced imaging, myocardial remodeling and therapeutic targeting using novel liposome-based peptide delivery system. Through this mechanism, Dr. Sharma will obtain support and training to elaborate the skills essential for him to become an independent investigator.

项目概要 该提案描述了 Umesh Sharma 博士的五年职业发展和培训计划 在 John M. Canty, Jr. 教授的指导下，Sharma 博士目前是该校的医学助理教授 大学在布法罗。他的职业发展计划利用了公司提供的广泛资源 布法罗大学和临床与转化研究中心汇集了一支强大的团队 具有小动物生理学、心肌重塑、治疗学和动力学专业知识的研究人员 磁共振成像。资助期间，Sharma博士将在该部门担任教职 布法罗大学心血管医学博士。他的目标是成为一名成功且独立的人 研究人员研究缺血引起的心肌损伤和功能障碍的机制，并确定新的 治疗目标。 获得该奖项将使 Sharma 博士获得小动物研究方面的额外培训， 全面的心脏组织和分子成像、生物统计学、研究设计和伦理学，并将促进 他向独立研究的转变。 Sharma 博士推测，在存在缺血性心肌的情况下 损伤后，过量的半乳糖凝集素 3 会促进心肌炎症和纤维化。阻断半乳糖凝集素 3 活性 基因突变或治疗拮抗剂可抑制炎症、减少纤维化并保留 心脏功能。 Sharma博士拥有丰富的研究记录并取得了出色的初步成果 这表明这种方法在小鼠心肌缺血模型中的可行性。总而言之，通过带来 汇聚前沿技术和全面的专家团队制定优秀的研究计划 和导师结构，夏尔马博士将能够协同融合先进成像领域， 使用新型脂质体肽递送系统进行心肌重塑和治疗靶向。通过 通过这个机制，夏尔马博士将获得支持和培训，以阐述他成为成为 独立调查员。