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. K02：独立科学家奖摘要候选人。鲁迪·m·奥尔蒂斯（Rudy M. Ortiz）博士是加州大学默塞德分校（University of California, Merced）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，也是21世纪第一个主要的研究机构。我于2005年加入UCM，是它的创始教师之一，是它的第一位西班牙裔教师，最近（2002 /09）成为UCM第一位获得R01 （NHLBI）的助理教授。父母赠款以北方象海豹为模型，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，如长时间禁食和呼吸暂停（包括睡眠和潜水引起的），这些条件可能会促进氧化应激及其相关病理。这些条件对人类来说是有害的，最终是致命的。的目标。这个奖项将允许我进一步扩展我的研究计划，利用保护时间学习和整合我们以前在实验室没有使用过的技术和技能，如qRT-PCR和高级色谱法。当我们开始探索这些技术时，受保护的时间将允许我将更多的时间集中在将这些技术作为实验室中稳定和常规的方法实现上。这将扩大我们的能力，提高我们科学的整体质量。提高我们的科学水平最终会提高我们的生产力，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年内）的目标。最终，我在未来2-3年内的目标是在剩余的职业生涯中获得足够的研究支持，以多个和并发的r级奖项的形式。这个水平的资金应该足以支持一个至少10名成员的研究团队，每年能够发表4-5篇论文。一旦我完全建立了我的研究事业和必要的技能和技术在我的实验室，我打算开发和指导外部资助的培训项目（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，从我在德州农工大学读本科开始就参与了这些项目，目前我参加了UCSC-MHIRT项目，这让我对这类项目有了丰富的经验。环境。我的实验室和我的合作者的实验室（在父母R01拨款中提到）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位资深的同事与我合作，我定期与他们会面，讨论资助的进展。反过来，他们提供延伸的指导和研究方向，以帮助确保我完全独立的研究。受保护的时间也将加强我的学生的训练，我将能够投入更多的时间来监督他们的研究，这是由家长资助的。研究。这个新提出的具体目标是评估嘌呤循环和HIF-1激活对北方象海豹对睡眠呼吸暂停引起的缺氧的自然耐受性的贡献。这一特定的目的将解决以下假设：海象通过回收睡眠呼吸暂停引起的缺氧产生的嘌呤核苷来避免潜在的自由基产生，以及睡眠呼吸暂停期间HIF-1被氧化还原依赖机制激活，以协调细胞对缺氧的稳态反应。