Independent Scientist Development Award in Oxidative Stress and Apnea

氧化应激和呼吸暂停独立科学家发展奖

• 批准号: 8118198
• 负责人: Rudy M Ortiz
• 金额: $ 10.37万
• 依托单位: UNIVERSITY OF CALIFORNIA, MERCED
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8118198
• 关键词: Address; Angiotensin II; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Apnea; Award; Behavior; Biomedical Research; Biopsy Specimen; CCL7 gene; California; Cardiovascular system; Chromatography; Chronic; Commit; DNA; Development; Diving; Environment; Equipment; Event; Experimental Water Deprivation; Faculty; Fasting; Food deprivation (experimental); Free Radicals; Funding; Gene Expression; Glutathione Disulfide; Goals; Grant; Guanine; Hispanics; Human; Hydrocortisone; Hypoxanthines; Hypoxia; Independent Scientist Award; Inflammation; Inflammatory; Inflammatory Response; Institution; Learning; Lipid Peroxidation; Mammals; Measures; Mentorship; Methodology; Minority Health and Health Disparities International Research Training; Mirounga; Modeling; Muscle; National Heart, Lung, and Blood Institute; Nuclear Protein; Oxidation-Reduction; Oxidative Stress; Paper; Parents; Pathology; Physiological; Physiology; Production; Productivity; Proteins; Purine Nucleosides; Purines; Recycling; Research; Research Support; Sampling; Science; Scientist; Sleep; Sleep Apnea Syndromes; Students; System; Techniques; Technology; Texas; Time; Tissues; Training; Training Programs; Transferase; Underrepresented Minority; Universities; Weaning; Xanthine Oxidase; Xanthines; abstracting; adduct; career; experience; glutathione peroxidase; improved; inflammatory marker; meetings; member; new therapeutic target; nutrition; parent grant; professor; programs; public health relevance; purine; respiratory; response; seal; skills

DESCRIPTION (provided by applicant): Ortiz, Rudy M. K02: Independent Scientist Award Abstract Candidate. Dr. Rudy M. Ortiz is an assistant professor of physiology and nutrition at the University of California, Merced, which is the 10th and newest campus of the University of California system and is the first major research institution of the 21st century. I joined UCM as a member of its founding faculty in 2005, was its first Hispanic faculty member, and recently (02/09) became the first assistant professor at UCM to be awarded an R01 (from NHLBI). The parent grant uses the northern elephant seal as a model for evaluating the physiological and cellular mechanisms some mammals have evolved that have allowed them to naturally adapt to extreme environmental conditions such as prolonged fasting and apnea (both sleep- and diving- induced) that may promote oxidative stress and its related pathologies. These are conditions that would otherwise be detrimental and eventually fatal in humans. Goals. This award will allow me to expand my research program further by using the protected time to learn and incorporate technologies and skills that we have not used previously in the lab such as qRT-PCR and advanced chromatography. While we have begun to explore these techniques, the protected time will allow me to focus more time on getting these techniques implemented as stable and routine methodologies in the lab. This will expand our capabilities and improve the overall quality of our science. Improving our science will ultimately increase our productivity and thus greatly enhance my chances of obtaining tenure, which is my relatively near-term (within the next 1-2 yrs) goal. Ultimately, my goal within the next 2-3 years is to have sufficient research support in the form of multiple and concurrent R-level awards for the remainder of my career. This level of funding should be sufficient to support a research team at least 10 members that is capable of producing 4-5 papers per year. Once I have fully established my research career and the requisite skills and techniques in my lab, I intend to develop and direct extramurally-funded training programs (such as MHIRT, MBRS and MARC) for underrepresented minorities as I continue my biomedical research. I consider my self a product of these programs having been involved with them since I was an undergraduate at Texas A&M and I currently participate in the UCSC-MHIRT program, which has given me extensive experience with such programs. Environment. My lab and that of my collaborators (mentioned in parent R01 grant) have all the space and equipment to required to accomplish the scientific goals of the proposed studies. I have 3 senior colleagues collaborating with me on the parent grant that I meet with regularly to discuss the progress of the grant. In turn, they provide extended mentorship and research direction to help insure my weaning to full research independence. The protected time will also enhance the training of my students I will be able to commit more time to supervising their research that is supported by the parent grant. Research. The goal of this newly proposed specific aim is to evaluate the contributions of purine recycling and HIF-1 activation to the northern elephant seal's natural tolerance against sleep apnea-induced hypoxia. This specific aim will address the hypothesis that elephant seals avoid potential free radical production by recycling purine nucleosides derived from sleep apnea- induced hypoxia, and that HIF-1 is activated by redox-dependent mechanisms during sleep apnea in order to coordinate the cellular homeostatic response against hypoxia. PUBLIC HEALTH RELEVANCE: Ortiz, Rudy M. K02: Independent Scientist Award Project Narative Elephant seals experience prolonged periods of food and water deprivation in addition to chronic sleep apnea-induced hypoxia, both of which can rapidly evoke cardiovascular and respiratory complications in humans. However, these seals must have evolved uniquely robust physiological and cellular mechanisms to counter the potentially detrimental consequences commonly associated with these behaviors. Elucidation of these mechanisms in seals may reveal novel therapeutic targets to help alleviate these consequences in humans. The proposed studies provide the initial steps towards developing the northern elephant seal as a viable biomedical model to study the natural adaptations evolved to counter oxidative stress and inflammatory events commonly induced by prolonged food deprivation and, sleep- and diving-associated hypoxia.

描述（由申请人提供）：Ortiz，Rudy M. K 02：独立科学家奖摘要候选人。Rudy M.博士Ortiz是加州大学默塞德分校生理学和营养学助理教授，默塞德分校是加州大学系统的第10个也是最新的校区，是21世纪世纪第一个主要的研究机构。我在2005年加入UCM作为其创始教师的一员，是它的第一个西班牙裔教师，最近（02/09）成为UCM的第一个助理教授被授予R 01（从NHLBI）。父母赠款使用北方象海豹作为模型，用于评估一些哺乳动物进化的生理和细胞机制，这些机制使它们能够自然适应极端环境条件，如长时间禁食和呼吸暂停（睡眠和潜水诱导），这可能会促进氧化应激及其相关病理。这些是否则会对人类有害并最终致命的条件。目标.该奖项将使我能够利用受保护的时间进一步扩展我的研究计划，学习和整合我们以前在实验室中没有使用过的技术和技能，如qRT-PCR和高级色谱。虽然我们已经开始探索这些技术，但受保护的时间将使我能够将更多的时间集中在将这些技术作为实验室中的稳定和常规方法实现上。这将扩大我们的能力，提高我们科学的整体质量。改进我们的科学将最终提高我们的生产力，从而大大提高我获得终身职位的机会，这是我相对近期（未来1-2年内）的目标。最终，我的目标是在未来2-3年内，在我的职业生涯的剩余时间里，以多个和并发的R级奖项的形式获得足够的研究支持。这一水平的资金应足以支持一个研究团队，至少有10名成员，每年能够产生4-5篇论文。一旦我已经完全建立了我的研究生涯和必要的技能和技术在我的实验室，我打算开发和指导校外资助的培训计划（如MHIRT，MBRS和MARC）为代表性不足的少数民族，因为我继续我的生物医学研究。我认为我自己是这些项目的产物，自从我在德克萨斯A&M读本科以来，我就一直参与这些项目，我目前参加了UCSC-MHIRT项目，这给了我丰富的经验。环境我的实验室和我的合作者的实验室（在父R 01资助中提到）拥有实现拟议研究的科学目标所需的所有空间和设备。我有3个资深同事与我合作的家长补助金，我定期会见，讨论补助金的进展。反过来，他们提供了扩展的指导和研究方向，以帮助确保我断奶，以充分的研究独立。受保护的时间也将加强我的学生的培训，我将能够投入更多的时间来监督他们的研究，这是由家长资助。Research.这项新提出的具体目标是评估嘌呤再循环和HIF-1激活对北方象海豹对睡眠呼吸暂停引起的缺氧的天然耐受性的贡献。这一特定目标将解决以下假设：海象通过回收源自睡眠呼吸暂停诱导的缺氧的嘌呤核苷来避免潜在的自由基产生，并且在睡眠呼吸暂停期间通过氧化还原依赖性机制激活HIF-1，以协调针对缺氧的细胞稳态响应。 公共卫生相关性：Ortiz，Rudy M. K02：独立科学家奖项目叙事象海豹经历长时间的食物和水剥夺，除了慢性睡眠呼吸暂停引起的缺氧，这两种情况都可以迅速引起人类的心血管和呼吸系统并发症。然而，这些海豹必须进化出独特的强大的生理和细胞机制，以对抗通常与这些行为相关的潜在有害后果。阐明海豹的这些机制可能会揭示新的治疗靶点，以帮助减轻人类的这些后果。拟议的研究提供了初步的步骤，发展北方象海豹作为一个可行的生物医学模型，研究自然的适应性演变，以对抗氧化应激和炎症事件通常引起的长期食物匮乏，睡眠和潜水相关的缺氧。