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Nitrite and Nitric Oxide in Sickle Cell Blood

镰状细胞血中的亚硝酸盐和一氧化氮

基本信息

批准号：
7328594
负责人：
DANIEL B KIM-SHAPIRO
金额：
$ 10.37万
依托单位：
WAKE FOREST UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-12-27 至 2009-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7328594
关键词：
Affect Behavior Binding Biochemical Biochemistry Biophysics Blood Blood flow Businesses Cell membrane Cells Chemicals Costs and Benefits Cysteine Data Doctor of Philosophy Educational process of instructing Enzyme Activation Enzymes Erythrocytes Fetal Hemoglobin Functional disorder Funding Future Goals Grant Hemoglobin Imaging Device Incubated Independent Scientist Award Individual Invasive Kinetics Laboratories Laws Membrane Methemoglobin Methods Microcirculation Modification Nitric Oxide Nitrites Nitrosation Oxygen Pathology Patients Pharmaceutical Preparations Physics Physiology Principal Investigator Production Property Publishing Rate Reaction Research Research Design Services Sickle Cell Sickle Cell Anemia Site Soluble Guanylate Cyclase Students Suspension substance Suspensions System Techniques Testing Therapeutic Therapeutic Effect Time Tissues United States Food and Drug Administration Universities Whole Blood Work base design forest hydroxyurea improved medical schools melting oxidation polymerization post-doctoral training professor programs sickling uptake

项目摘要

DESCRIPTION (provided by applicant): The candidate will have his teaching and service load reduced so that he can spend greater than 75% of his time on research. After earning a M.S. in physics, the candidate earned a Ph.D. in biophysics at UC Berkeley in 1993. He began studying sickle cell disease during his NIH-funded postdoctoral training. He has continued his focus on sickle cell disease since joining the Physics Department at Wake Forest University in 1996. Wake Forest University has about 3800 undergraduates, 600 graduate students, and 1,500 students in the professional schools of medicine, law, and business. The candidate currently has a spacious laboratory and office as a tenured Associate Professor of Physics. He is currently the principal investigator (PI) on a NIH-funded grant (R01 HL58091) focusing on the effects of nitric oxide (NO) in sickle cell blood. Patients with sickle cell anemia have been shown to have abnormal NO-related vasoactivity due to the scavenging of NO by cell-free hemoglobin. NO therapy may restore normal NO vasoactivity, and data has also recently been published suggesting that NO may upregulate fetal hemoglobin and thereby reduce sickling. The candidate is also a key collaborator on a study of the NO donating properties of hydroxyurea (an FDA approved drug for sickle cell disease). In addition, the candidate will expand his studies looking at the effects of NO in sickle cell blood by looking at the effects of nitrite as converted to NO by deoxygenated hemoglobin and thus serves as a reservoir for NO in the body. Finally, the candidate plans to develop non-invasive imaging tools to study pathology of the microcirculation in patients with sickle cell disease and the effects of therapeutics. The candidate currently has a heavy teaching and service load. A K02 award will relieve him of some of these duties so that he can spend more time interacting with his colleagues, attending seminars and meetings, and doing research.

描述（由申请人提供）：候选人将有他的教学和服务负荷减少，使他可以花费超过75%的时间在研究上。获得MS后在物理学方面，这位候选人获得了博士学位。1993年在加州大学伯克利分校的生物物理学。他在NIH资助的博士后培训期间开始研究镰状细胞病。自1996年加入维克森林大学物理系以来，他一直专注于镰状细胞病。维克森林大学有大约3800名本科生，600名研究生，以及1,500名医学，法律和商业专业的学生。候选人目前拥有一个宽敞的实验室和办公室作为物理学终身副教授。他目前是NIH资助的赠款（R 01 HL 58091）的主要研究者（PI），专注于镰状细胞血液中一氧化氮（NO）的影响。镰状细胞性贫血患者由于无细胞血红蛋白清除NO而表现出异常的NO相关血管活性。 NO治疗可以恢复正常的NO血管活性，最近发表的数据也表明NO可以上调胎儿血红蛋白，从而减少镰状化。候选人也是一个关键的合作者在一项研究的NO捐赠性质的羟基脲（FDA批准的药物镰状细胞病）。此外，候选人将通过研究亚硝酸盐通过脱氧血红蛋白转化为NO的影响来扩大他对镰状细胞血液中NO影响的研究，从而作为体内NO的储存库。最后，候选人计划开发非侵入性成像工具，以研究镰状细胞病患者的微循环病理学和治疗效果。候选人目前有沉重的教学和服务负荷。 K 02奖将减轻他的一些职责，使他可以花更多的时间与同事互动，参加研讨会和会议，并做研究。