Nitrite and Nitric Oxide in Sickle Cell Blood

镰状细胞血中的亚硝酸盐和一氧化氮

• 批准号: 6848917
• 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
• 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/6848917
• 关键词: blood /lymphatic pharmacology; blood disorder chemotherapy; chemical reaction; clinical research; hemoglobin; human subject; hydroxyurea; imaging /visualization /scanning; microcirculation; nitric oxide; nitrites; noninvasive diagnosis; sickle cell anemia

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）： 候选人的教学和服务负担将减少，这样他就可以将75%以上的时间用于研究。 获得硕士学位后在物理学方面，候选人获得了博士学位。 1993 年，他在加州大学伯克利分校获得生物物理学博士学位。在 NIH 资助的博士后培训期间，他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，他继续关注镰状细胞病。维克森林大学拥有约 3800 名本科生、600 名研究生以及 1,500 名医学、法律和商学院专业学生。 该候选人目前拥有宽敞的实验室和办公室，担任物理学终身副教授。 他目前是 NIH 资助的一项拨款 (R01 HL58091) 的首席研究员 (PI)，重点研究镰状细胞血中一氧化氮 (NO) 的影响。 由于无细胞血红蛋白清除 NO，镰状细胞性贫血患者已被证明具有异常的 NO 相关血管活性。 NO 疗法可以恢复正常的 NO 血管活性，最近发表的数据表明，NO 可以上调胎儿血红蛋白，从而减少镰状化。 该候选人还是羟基脲（FDA 批准的治疗镰状细胞病的药物）NO 捐赠特性研究的重要合作者。 此外，候选人将通过观察亚硝酸盐通过脱氧血红蛋白转化为一氧化氮并因此作为体内一氧化氮的储存库的影响来扩展他的研究，以观察镰状细胞血中一氧化氮的影响。 最后，候选人计划开发非侵入性成像工具来研究镰状细胞病患者微循环的病理学和治疗效果。 候选人目前的教学和服务负担很重。 K02 奖项将免除他的部分职责，以便他可以花更多时间与同事互动、参加研讨会和会议以及进行研究。