BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 10513328
• 负责人: YANG K XIANG
• 金额: --
• 依托单位: VA NORTHERN CALIFORNIA HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-10-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10513328
• 关键词: ADRBK1 gene; Adrenergic Agents; Adrenergic Receptor; Alzheimer' s Disease; Amyloid beta-Protein; Angiotensins; Animal Model; Asthma; Atrial Fibrillation; Award; Biosensor; Brain; California; Cardiac; Cardiac Myocytes; Cardiac Output; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cell physiology; Chronic; Chronic Disease; Chronic Obstructive Pulmonary Disease; Circulation; Clinical; Clinical Trials; Cognition; Collaborations; Complex; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cyclic GMP; DLG1 gene; Data; Depressed mood; Development; Diabetes Mellitus; Disease; Drug Screening; EFRAC; Emotions; Epinephrine; Fibrosis; Functional disorder; Funding; GRK5 gene; Genes; Genetic; Genomics; Goals; Grant; Health; Health Care Costs; Heart Diseases; Heart failure; Homeostasis; Hormones; Human; Hyperglycemia; Hyperinsulinism; Impairment; Inflammation; Inflammatory; Insulin; Insulin Receptor; Interleukin-1 beta; Intervention; Investigation; Joints; Laboratories; Learning; Link; Longevity; Membrane Proteins; Memory; Memory Loss; Mentors; Metabolic; Metabolic Diseases; Metabolic syndrome; Metabolism; Molecular; Molecular Target; Muscle Cells; Nature; Nerve; Neurodegenerative Disorders; Neurohormones; Neurons; Nitric Oxide; Outcome; Pain; Parkinson Disease; Pathogenesis; Pathologic; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Physicians; Prevention strategy; Privatization; Prostaglandins; Proteins; Proteomics; Protocols documentation; Quality of life; Receptor Signaling; Regulation; Research; Research Personnel; Role; Science; Scientist; Services; Signal Induction; Signal Pathway; Signal Transduction; Signaling Molecule; Stress; Synapses; System; Therapeutic; Therapeutic Intervention; Tissues; Transgenic Model; Translating; United States National Institutes of Health; Veterans; alpha synuclein; beta-2 Adrenergic Receptors; beta-adrenergic receptor; biochemical tools; career; clinical practice; cognitive function; comorbidity; cytokine; desensitization; diabetic; diabetic patient; flexibility; heart function; hormone regulation; improved; inhibitor; insight; insulin signaling; interest; live cell imaging; military veteran; neurotoxicity; new therapeutic target; novel; novel strategies; novel therapeutic intervention; programs; protein complex; receptor; response; single molecule; spatiotemporal; synuclein

The overall goal of my research is to understand mechanisms underlying pathophysiology in chronic diseases, in particular heart failure (HF) and Alzheimer’s disease (AD). I aim to discover unknowns, establish new paradigms, and identify novel targets for drug screening and clinical therapy. We apply integrative approaches that include single molecule analysis, live-cell imaging, genomic and proteomic analysis, and transgenic model animals to understand the fundamentals of intracellular signaling networks and their functional roles in development of diseases. Over the past 16 years, I have received continuous funding from NIH, VA, and private agencies. I am currently supported by two NIH R01 grants, a VA merit award, and a joint California TRDRP grant. The results from my laboratory have significantly deepened our understanding of signaling regulation and offered novel therapeutic targets for HF and AD. Through these endeavors, I have received an AHA established investigator award in 2010 and established myself as a global leader in cardiac signaling transduction. In the early years, my research focuses on novel features of cardiac beta-adrenergic receptor (bAR) signaling such as spatiotemporal regulation of cAMP-PKA cascades in cardiac contractile function. Over the past 10 years, I have expanded my research program to understand regulatory signaling networks in disease development under chronic conditions such as inflammation and metabolic disorders. One of the highlights is that we have described a membrane protein complex of insulin receptor (InsR) and b2AR broadly expressed in different tissues. Activation of b2AR and InsR are critical regulatory mechanisms of both cardiovascular function and metabolism. These receptors also modulate cognitive function including memory and learning, pain, emotion and stress in the central nerve system. Dysregulation of these receptor signaling pathways has been linked to development of HF and AD. Our recent studies have opened an exciting avenue in understanding cardiovascular complications and neurodegenerative diseases associated with diabetes and metabolic syndromes. Several active projects below are supported by ongoing funding from NIH and VA. The current VA merit grant aims to characterize the essential roles of two proteins GRK5 and SAP97 in reduction (desensitization) of adrenaline stimulation of a signaling molecule nitric oxide to enhance cardiac output. We will find how this regulation goes wrong in heart diseases and thus offers novel strategies to treat heart diseases.

我研究的总体目标是了解慢性阻塞性肺疾病的病理生理机制