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: 7960883
• 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/7960883
• 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; 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; Nuclear Proteins; 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. K02：独立科学家奖摘要候选人。 Rudy M. Ortiz博士是加利福尼亚大学默塞德分校的生理学和营养助理教授，这是加利福尼亚大学系统的第十和最新校园，是21世纪的第一家主要研究机构。我于2005年加入UCM，成为其创始学院的成员，是其第一位西班牙裔教师，最近（02/09）成为UCM的第一任助理教授，被授予R01（来自NHLBI）。父母的赠款使用北方大象密封作为评估一些哺乳动物的生理和细胞机制的模型，这些哺乳动物已经进化，使它们自然适应了极端环境条件，例如长时间的禁食和呼吸暂停（均可诱导的睡眠和潜水），这些疗程可能促进氧化应激及其相关的病理学。这些条件否则在人类中会有害并最终致命。目标。该奖项将使我能够使用受保护的时间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，例如QRT-PCR和高级色谱法。尽管我们开始探索这些技术，但受保护的时间将使我能够将更多的时间集中在实验室中以稳定和常规的方法来实现这些技术。这将扩大我们的能力并提高我们科学的整体质量。改善我们的科学将最终提高我们的生产率，从而大大增加我获得任期的机会，这是我相对近期（在接下来的1 - 2年内）目标。最终，在未来2 - 3年内，我的目标是在我的职业生涯中以多个和同时的R级奖项的形式获得足够的研究支持。这一水平的资金应该足以支持至少10个能够每年生产4-5篇论文的研究团队。一旦我在实验室中充分建立了自己的研究生涯以及必要的技能和技术，我打算为代表性不足的少数群体开发和直接制定和指导诸如MHIRT，MBRS和MARC）的培训计划（例如MHIRT，MBRS和MARC）。我认为我的自我是这些计划的产品，因为我是德克萨斯A＆M的本科生，而我目前参加了UCSC-Mhirt计划，这为我提供了这些计划的丰富经验。环境。我的实验室和我的合作者（在父级R01赠款中提到）的实验室拥有所有实现拟议研究的科学目标所需的空间和设备。我有3位高级同事与我合作，在父母赠款上与我定期会面，讨论赠款的进度。反过来，它们提供了扩展的指导和研究方向，以帮助确保我的断奶为完全研究独立性。受保护的时间还将增强对我的学生的培训，我将能够花更多的时间来监督父母赠款支持的研究。研究。这个新提出的特定目的的目的是评估嘌呤回收和HIF-1激活对北象密封件对睡眠呼吸呼吸暂停诱导的缺氧的自然耐受性的贡献。该特定目的将解决以下假设：大象密封剂通过回收从睡眠呼吸暂停诱导的缺氧而得出的嘌呤核苷来避免潜在的自由基生产，并且HIF-1在睡眠呼吸暂停期间被氧化还原依赖性机制激活，以协调针对低氧的细胞稳态反应。 公共卫生相关性：Ortiz，Rudy M. K02：独立科学家奖项目narative Elephant Seals经历了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，这两者都可以快速唤起人类的心血管和呼吸系统并发症。但是，这些密封必须发展出独特的鲁棒生理和细胞机制，以应对通常与这些行为相关的潜在有害后果。密封中阐明这些机制可能会揭示新的治疗靶标，以帮助减轻人类的这些后果。拟议的研究提供了开发北象密封的初步步骤，作为一种可行的生物医学模型，以研究与氧化应激和炎症事件相反，通常是由于长期食物剥夺以及与睡眠和潜水相关的缺氧所引起的。