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

项目摘要 该提案描述了Umesh Sharma博士的五年职业发展和培训计划， 约翰·M教授的指导。小坎蒂夏尔马博士目前是医学助理教授， 布法罗大学。他的职业发展计划利用了 布法罗的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 磁共振成像在资助期间，Sharma博士将在该司担任教职 他是布法罗大学心血管医学系的主任。他的目标是成为一个成功和独立的 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博士假设，在存在缺血性心肌 损伤时，过量的半乳糖凝集素-3促进心肌炎症和纤维化。通过以下途径阻断半乳糖凝集素-3活性 基因突变或治疗性拮抗作用可抑制炎症，减少纤维化， 心脏功能Sharma博士拥有强大的研究记录，并获得了出色的初步结果 显示了这种方法在小鼠心肌缺血模型中的可行性。总之，通过将 汇聚尖端技术和全面的专家团队，制定优秀的科研计划 和指导结构，夏尔马博士将能够协同合并先进的成像领域， 心肌重塑和治疗靶向使用新的脂质体为基础的肽传递系统。通过 通过这一机制，夏尔马博士将获得支持和培训，以阐述他成为 独立调查员

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.