权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

基本信息

批准号：
10337065
负责人：
Anjaneyulu Kowluru
金额：
--
依托单位：
JOHN D DINGELL VA MEDICAL CENTER
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：
2020-10-01 至 2027-09-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10337065
关键词：
Address Affect American Animal Model Apoptotic Area Attenuated Award Beta Cell Biochemical Pharmacology Biological Caring Catalytic Domain Cell model Cell physiology Cells Cellular Metabolic Process Ceramides Chronic Collaborations Complex Data Defect Development Diabetes Mellitus Diabetic Retinopathy Diabetic mouse Disease Endocrine Endocrinology Endothelial Cells Environment Exposure to Failure Functional disorder Future GTP-Binding Proteins Glucose Guanine Nucleotide Dissociation Inhibitors Health Healthcare Healthcare Systems Human Hyperglycemia Impairment In Vitro Incidence Individual Insulin Insulin Resistance International Investigation Journals Knowledge Laboratories Lipids Mediating Medical Mentors Metabolic Metabolic Diseases Metabolic dysfunction Metabolic stress Metabolism Methodology Methylation Microscopic Mission Mitochondria Molecular Monomeric GTP-Binding Proteins Non-Insulin-Dependent Diabetes Mellitus Nuclear Obesity Oxidative Stress Pathogenesis Pathway interactions Peer Review Peptides Peripheral Physiological Physiology Post-Traumatic Stress Disorders Prevention Protein phosphatase Proteins Proteomics Publications Publishing Regulation Reporting Research Research Personnel Retina Rodent Role Saturated Fatty Acids Scientist Seminal Signal Pathway Signal Transduction Signaling Protein Sphingolipids Structure of beta Cell of islet Therapeutic Time Tissues Training Transcriptional Activation Veterans Veterans Health Administration Work Writing base career diabetic diet-induced obesity exhaustion functional loss high risk impaired glucose tolerance in vivo in vivo Model indexing inhibitor innovation insight insulin granule insulin secretion islet lipidomics meetings military veteran mitochondrial dysfunction next generation novel novel therapeutic intervention prenylation prevent programs protein activation response restoration small molecule small molecule inhibitor therapeutic target trafficking

项目摘要

Diabetes is a serious medical condition resulting from failure of insulin action and/or insufficient insulin secretion from the pancreatic β-cells. Diabetes affects approximately 20% of the Veterans that receive health care through the Veterans Health Administration. Therefore, efforts to understand the pathophysiology of this debilitating disease are highly relevant to future developments in care and therapeutics of this disease. The PI has been conducting diabetes research for nearly 30 years. His current investigations are aimed at understanding the molecular and cellular mechanisms underlying β-cell dysfunction leading to the onset of diabetes. Seminal contributions from his laboratory have defined novel roles for Rac1, a small G-protein, in the pathogenesis of islet β-cell dysfunction under metabolic stress and diabetic conditions. His current studies are based on the hypothesis that metabolic stress promotes functional and transcriptional activation of Rac1 to promote intracellular oxidative stress, mitochondrial and nuclear damage/ collapse leading to the loss of functional β-cell mass. His team is also aiming to identify key signaling proteins/factors in the Rac1 activation- deactivation cycle that might contribute to the metabolic and functional defects in the pancreatic β-cell. These studies employ state-of-the art microscopic, molecular biological, proteomics and lipidomics approaches involving islets derived from animal models of impaired insulin secretion as well as islets from T2D human donors. In addition to his ongoing investigations (above), during the next renewal period, the PI will continue collaborative studies toward the development of novel small molecule and peptide-based inhibitors for halting metabolic defects of the islet β-cell in in vitro and in vivo models of metabolic stress and diabetes. The long-standing expertise of the PI and his collaborators in this field will provide a unique opportunity to address these important aspects of islet function in health and diabetes. Furthermore, the PI will continue his ongoing, highly productive, collaborative studies to decipher the molecular and cellular mechanisms involved in the pathogenesis of diabetic retinopathy. Lastly, the PI proposes to establish new collaborations with researchers at the JDD VAMC to assess islet β-cell function in animal models of TBI and PTSD. Significant knowledge gaps exist in this area, which is highly relevant to the VA healthcare mission. Collectively, data accrued from these complementary investigations will provide actionable insights that will impact the prevention and treatment of diabetes and its associated complications in humans, including our Veterans. In support of the proposed investigations, the PI has already established numerous collaborations with VA and non-VA investigators. He is highly productive with a large number of publications in high impact journals; the majority of which are coauthored by his trainees and collaborators. He wrote authoritative reviews on these topics in leading journals including Endocrine Reviews, Diabetes, Obesity and Metabolism, and Comprehensive Physiology. In summary, this application seeks renewal of Dr. Kowluru’s a well-established and highly recognized SRCS program for studies on pathophysiology of diabetes and its associated complications, which is a high priority program for our VA healthcare system.

糖尿病是一种由胰岛素作用失败和/或胰岛素不足引起的严重疾病