IRE1 RNase 部分拮抗剂（PAIR）治疗 1 型糖尿病-猫眼课题宝

IRE1 RNase 部分拮抗剂（PAIR）治疗 1 型糖尿病

批准号：

10239016

负责人：

Dustin J Maly

金额：

$72.69万

依托单位：

UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

依托单位国家：

美国

项目类别：

财政年份：

2019

资助国家：

美国

项目状态：

已结题

起止时间：

2019-09-20 至 2023-07-31

来源：

https://reporter.nih.gov/project-details/10239016

关键词：

Adopted Apoptosis Automobile Driving B-Lymphocytes Beta Cell Binding Biochemical Cell Differentiation process Cell Survival Cells Cellular Assay Cessation of life Chemicals Clinic Clinical Clinical Trials Clinical Trials Design Collaborations Cytoprotection Development Diabetes Mellitus Disease Progression Dose Endoplasmic Reticulum Endoribonucleases Event Generations Genetic Transcription Grant Harvest Homeostasis Human Hyperactivity Hyperglycemia Immune Targeting Immune mediated destruction Immune system In Vitro Inbred NOD Mice Inflammation Insulin Insulin-Dependent Diabetes Mellitus Integral Membrane Protein Islets of Langerhans Laboratories Lead Measures Membrane Messenger RNA Modeling Molecular Conformation Mus Outcome Output Pancreatic ribonuclease Patients Pharmaceutical Preparations Pharmacology Phosphotransferases Physiological Prevention Production Proinsulin Proteins RNA RNA Splicing Reaction Reagent Research Personnel Ribonucleases Secretory Cell Secretory Rate Series Signal Pathway Slice Stress Structure Structure of beta Cell of islet Suicide System Taxes Testing Therapeutic Transplantation Work XBP1 gene autoimmune pathogenesis autoreactivity base cellular targeting chronic autoimmune disease design diabetes pathogenesis dimer endoplasmic reticulum stress inhibitor/antagonist islet kinase inhibitor male monomer novel preservation prevent programs protein folding response secretory protein small molecule transcription factor treatment optimization

项目摘要

项目成果

Dustin J Maly的其他基金

相似基金

相关文献

中文摘要

翻译

点击翻译按钮获取中文摘要

英文摘要

PROJECT SUMMARY/ABSTRACT Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by hyperglycemia due to progressive immune-mediated destruction of pancreatic beta cells. Recent work from our laboratories has shown that hyperactivation of the unfolded protein response (UPR) to ER stress in the immune-targeted beta cells may be a critical early event in the development of T1D. We have developed novel pharmacological reagents called `PAIR's that allow us to manipulate components of the UPR. Importantly, first generation versions of small molecules—called KIRAs— delivered to NOD mice can efficaciously prevent and even reverse diabetes in this T1D model. Thus, in this collaborative grant we will capitalize on the complementary expertise of the investigators to optimize these PAIR lead molecules for potency and selectivity, conduct proof of concept studies using human islets, and perform key enabling steps needed to advance these candidates further into the clinic for treating human patients with T1D.

期刊论文(0)

专著(0)

科研奖励(0)

会议论文