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: 8267031
• 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/8267031
• 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. K02：独立科学家奖摘要候选人。 Rudy M. Ortiz 博士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 个也是最新的校园，也是 21 世纪第一个主要研究机构。我于 2005 年作为创始教员加入 UCM，是第一位西班牙裔教员，最近（02/09）成为 UCM 第一位被授予 R01（来自 NHLBI）的助理教授。家长资助使用北象海豹作为模型来评估一些哺乳动物进化出的生理和细胞机制，这些机制使它们能够自然地适应极端环境条件，例如长时间禁食和呼吸暂停（睡眠和潜水引起的），这些条件可能会导致促进氧化应激及其相关病理。否则这些情况会对人类有害并最终致命。目标。该奖项将使我能够利用受保护的时间学习和整合我们以前在实验室中未使用过的技术和技能，例如 qRT-PCR 和高级色谱法，从而进一步扩展我的研究计划。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时间集中在将这些技术作为稳定的常规方法在实验室中实施。这将扩大我们的能力并提高我们科学的整体质量。提高我们的科学水平最终将提高我们的生产力，从而大大提高我获得终身教职的机会，这是我相对近期（未来 1-2​​ 年）的目标。最终，我在未来 2-3 年内的目标是在我余下的职业生涯中以多个并发 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一个至少有 10 名成员的研究团队，每年能够发表 4-5 篇论文。一旦我在实验室中完全确立了我的研究生涯和必要的技能和技术，我打算在继续我的生物医学研究的同时，为代表性不足的少数群体开发和指导校外资助的培训计划（例如 MHIRT、MBRS 和 MARC）。我认为我自己是这些项目的产物，自从我在德克萨斯农工大学读本科时就参与其中，目前我正在参加 UCSC-MHIRT 项目，该项目给了我在此类项目方面的丰富经验。环境。我的实验室和我的合作者的实验室（在母 R01 资助中提到）拥有完成拟议研究的科学目标所需的所有空间和设备。我有 3 名资深同事与我合作处理家长补助金问题，我定期与他们会面讨论补助金的进展情况。反过来，他们提供了长期的指导和研究方向，以帮助确保我摆脱完全的研究独立性。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由家长资助支持的研究。研究。这一新提出的具体目标的目的是评估嘌呤循环和 HIF-1 激活对北象海豹对睡眠呼吸暂停引起的缺氧的自然耐受性的贡献。这一具体目标将解决以下假设：象海豹通过回收来自睡眠呼吸暂停引起的缺氧的嘌呤核苷来避免潜在的自由基产生，并且 HIF-1 在睡眠呼吸暂停期间通过氧化还原依赖性机制激活，以协调细胞稳态反应对抗缺氧。 公共健康相关性：Ortiz，Rudy M. K02：独立科学家奖项目叙事象海豹除了长期睡眠呼吸暂停引起的缺氧外，还经历了长时间的食物和水缺乏，这两种情况都会迅速引发人类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，以应对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。拟议的研究为将北象海豹开发为可行的生物医学模型提供了初步步骤，以研究为对抗氧化应激和炎症事件而进化的自然适应，这些氧化应激和炎症事件通常由长期食物匮乏以及睡眠和潜水相关的缺氧引起。