BLR&D Merit Review Research Career Scientist Award Application

BLR

基本信息

批准号：
10454104
负责人：
Hemal H Patel
金额：
--
依托单位：
VA SAN DIEGO HEALTHCARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10454104
关键词：
7 year old A kinase anchoring protein Acute Age Aging American Heart Association Applications Grants Area Award Biochemical Biological Assay Biology Biology of Aging Blood Circulation Blood Vessels Cancer Biology Cardiac Cardiac Myocytes Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Caveolae Caveolins Cell physiology Cells Cellular biology Clinical Communities Complex Development Diabetes Mellitus Disease Electron Microscopy Electrons Etiology Event Fellowship Frameshift Mutation Functional disorder Funding Future General Population Genus Hippocampus Grant Health Healthcare Heart Heart Diseases Heart Hypertrophy Heart Injuries Human Hypertrophy Injury Institution International Intervention Investigation Ischemia Journals Kidney Kidney Failure Laboratories Lead Link Lipids Liver diseases Lung Lung diseases Malignant Neoplasms Manuscripts Mediator of activation protein Membrane Membrane Microdomains Metabolic Metabolism Mitochondria Molecular Molecular Target Morbidity - disease rate Mus Muscle Mutation Myocardium Nature Neonatal Nephrology Nerve Degeneration Neurosciences Operative Surgical Procedures Opioid Organ Paper Pathology Pathway interactions Patients Peer Review Pharmacology Phosphotransferases Physiology Postdoctoral Fellow Predisposition Process Progeria Protein Isoforms Proteins Publications Publishing Pulmonary Hypertension Regulation Reperfusion Injury Research Research Personnel Respiration Risk Factors Role Scientist Secondary to Severities Smooth Muscle Myocytes Stress Structural Protein Structure System Techniques Therapeutic Time Transgenic Mice Translating Urology Vascular Smooth Muscle Vesicle Veterans Viral Vector Work aged body system brain cell cardiovascular risk factor career caveolin-3 cell growth comorbidity endothelial dysfunction exosome experience experimental study healthy aging heart cell heart function high risk insight interest military veteran mitochondrial metabolism mortality muscle physiology myocardial injury novel overexpression primary pulmonary hypertension response stressor targeted treatment tool

项目摘要

As the general population and veterans age, their hearts will undergo dramatic changes that will reduce their capacity to work efficiently and increase their susceptibility to injury. In addition, there are a number of co- morbidities such as diabetes that ensue with age that will further impact the heart and its adaptation to stress. Interventions that help to protect the heart from injury are likely to be useful in patients at high risk for cardiovascular events. Along with the general population, as veterans age, there will be an increasing burden of healthcare associated with age that lead to cardiovascular dysfunction. There are a number of molecular targets that may be critical in protection of the myocardium to stress but a unifying factor has been elusive, and thus a pharmacologic target not well defined. It is possible that multiple pathways of stress adaptation share an interconnected mediator that may be targeted therapeutically. The Patel Laboratory has been focused on identifying novel and unique mediators that regulate a multitude of pathways and may therefore be viable therapeutic endpoints for cardiovascular disease. The laboratory has a specific interest in caveolin and A- kinase interacting protein. There is clear clinical implication and need for interventions that limit the severity of injury that occurs to the myocardium, as this is a major risk factor to morbidity and mortality. Interventions that help to protect the heart are likely to be useful in many patients. Also, the basic nature of the studies underway in the Patel Laboratory to understand the fundamental physiology of the cell may also be broadly applicable to others organs and disease systems including but not limited to cancer biology, neurodegeneration, nephrology, urology, muscle physiology, pulmonary diseases, and the biology of aging. The Patel Laboratory has been specifically interested in assessing the impact of caveolae, membrane microdomains enriched in lipids and the structural protein caveolin, on cardiac physiology and pathophysiology for over a decade. Ongoing and collaborative studies with other national and international institutions has resulted in expansion in multiple organ systems and the potential to translate basic findings to a number of clinical problems. In 2004 Dr. Patel performed a very simple experiment where caveolae disruption showed that both ischemia- and opioid-induced cardiac protection was lost. This single experiment launched further inquiry into defining the role of caveolae in the heart especially as it relates to disease pathology;; this was the initial research funded by a Scientist Development Grant from the American Heart Association. The laboratory has sustained and expanded this focus over the years to uncover fundamental biology to define the role of caveolae in cardiac disease and develop tools to target this therapeutically. The Patel Laboratory has also uncovered a specific, critical, and interconnected role of caveolin in regulating cellular metabolism that is being applied to more complex studies related to neuroscience, cancer, diabetes, aging, and renal biology.

随着普通民众和退伍军人年龄的增长，他们的心脏将发生巨大的变化，从而降低他们的有效工作的能力和增加他们受伤的可能性。随着年龄的增长而出现的糖尿病等疾病将进一步影响心脏及其对压力的适应能力。有助于保护心脏免受损伤的干预措施可能对心脏病高危患者有用。与普通人群一样，随着退伍军人年龄的增长，心血管负担也会越来越重。与年龄相关的医疗保健会导致心血管功能障碍。有许多分子因素。可能对保护心肌免受应激至关重要的目标，但统一因素一直难以捉摸，并且因此，药理学目标没有明确定义。压力适应的多种途径可能共享一个可能是治疗目标的相互关联的介质。帕特尔实验室一直专注于识别新颖且独特的调节多种途径的介质，因此可能是可行的心血管疾病的治疗终点。实验室对 caveolin 和 A- 有特殊兴趣激酶相互作用蛋白具有明确的临床意义，并且需要采取干预措施来限制其严重程度。心肌损伤，因为这是发病率和死亡率的主要危险因素。有助于保护心脏可能对许多患者有用此外，地下研究的基本性质。在帕特尔实验室了解细胞的基本生理学也可能广泛适用于其他器官和疾病系统，包括但不限于癌症生物学、神经退行性疾病、肾病学、泌尿学、肌肉生理学、肺部疾病和衰老生物学。帕特尔实验室特别感兴趣的是评估小凹、膜的影响。富含脂质和结构蛋白caveolin的微结构域对心脏生理学和病理生理学的影响十多年来，与其他国家和国际机构正在进行持续的合作研究。导致多个器官系统的扩展，并有可能将基本发现转化为许多 2004 年，Patel 博士进行了一项非常简单的实验，结果显示小窝破裂。缺血和阿片类药物引起的心脏保护都丧失了。这个实验进一步启动了探究定义小窝在心脏中的作用，特别是它与疾病病理学的关系；；初步研究由美国心脏协会实验室的科学家发展补助金资助。多年来持续并扩大了这一重点，以揭示基础生物学来定义帕特尔实验室还开发了治疗心脏病的工具。揭示了 Caveolin 在调节细胞代谢中的特定、关键和相互关联的作用，该作用正在被研究应用于与神经科学、癌症、糖尿病、衰老和肾脏生物学相关的更复杂的研究。