Mentoring Emerging Researchers at CHLA (MERCH-LA)

指导 CHLA (MERCH-LA) 的新兴研究人员

基本信息

批准号：
10797938
负责人：
Senta K Georgia
金额：
$ 9.85万
依托单位：
CHILDREN'S HOSPITAL OF LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-15 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10797938
关键词：
2019-nCoV Acute Address Affect African American Animal Model Animals Atrophic Autopsy Award Awareness Beta Cell Biological Models Biological Sciences Biomedical Research COVID-19 COVID-19 impact COVID-19 pathogenesis COVID-19 patient COVID-19 survivors Cadaver Career Mobility Cell Respiration Cell Survival Cell physiology Cellular Metabolic Process Cessation of life Clinical Competence Data Development Diabetes Mellitus Diabetic Ketoacidosis Disease Education Environment Face Functional disorder Future Glucose Goals Health Human Hyperglycemia In Vitro Infection Injury Insulin Islets of Langerhans Transplantation Kidney Laboratories Literature Long COVID Los Angeles Macaca mulatta Measures Mediating Mentors Metabolic Metabolism Mission Mitochondria Modeling Molecular Morphology Mus Non-Insulin-Dependent Diabetes Mellitus Odds Ratio Outcome Pancreas Paper Pathogenesis Pathology Patients Pediatric Hospitals Physiological Post-Acute Sequelae of SARS-CoV-2 Infection Predisposition Prevalence Principal Investigator Public Health Reporting Reproducibility Research Research Infrastructure Research Personnel Research Project Grants Research Training Resolution Respiratory System SARS-CoV-2 infection SARS-CoV-2 pathogenesis Secondary to Stress Structure Structure of beta Cell of islet Study models Symptoms Techniques Testing Time Training Transplantation Viral Pathogenesis Woman blood glucose regulation capsule career career preparation clinical phenotype clinically relevant diabetes pathogenesis empowerment experience experimental study graduate student improved in vivo in vivo Model innovation insight insulin secretion islet long term consequences of COVID-19 long term recovery next generation nonhuman primate post-transplant programs severe COVID-19 skills small molecule student mentoring time use

项目摘要

PROJECT SUMMARY Beta cell dysfunction and death are significant pathologies underlying the development of Type 2 diabetes. There is both clinical and molecular evidence that the pathogenesis of COVID19 may have acute and specific effects on pancreatic beta cell function. One of the barriers to understanding how SARS-CoV2 infection may affect beta cell function and survival in patients is the limited number of physiologically relevant animal models to study. We have capitalized on unique access the pancreas of SCV2-innoculated animals to model and understand how SARS-CoV2 infection affects beta cell survival, metabolism, and function. There is controversy in the literature regarding if SARS-COV2 directly infects beta cells and affects beta cell function and survival or if the disruption of glucose homeostasis in patients is secondary. We hypothesize that SARS-CoV2 infection directly and acutely compromises beta cell function and survival by reprogramming cellular metabolism, thus leaving hosts susceptible to diabetes during or after infection. These highly innovative experiments capitalize on a unique and clinically relevant model system and employs cutting edge techniques to assess how beta cell survival and metabolism are affected by SARS-CoV2 infection. These experiments will provide critical mechanistic insight to the underpinnings of the emerging clinical phenotype of acute hyperglycemia, diabetic ketoacidosis, and potentially lifelong diabetes that may afflict a significant number of patients who have recovered from COVID19. The objective of this proposal is to protect the PI’s time to provide culturally-aware mentoring and intensive training to graduate students from historically underrepresented backgrounds participating in this innovative research program. This objective dovetails with the PI’s immediate and long terms goals, which are to: (1) establish MERCH-LA (Mentoring Emerging Researchers at Children’s Hospital Los Angeles) as a fundamental part of the educational and research infrastructure at CHLA and (2) longitudinally track and quantify outcomes for MERCH-LA graduates into bioscience-related post-graduate careers.

项目摘要 β细胞功能障碍和死亡是2型糖尿病发展的重要病理。有临床和分子证据表明，covid19的发病机理可能具有急性和特异性对胰腺β细胞功能的影响。了解SARS-COV2感染的障碍之一影响β细胞功能和患者的存活是有限的物理相关动物模型学习。我们已经利用了独特的访问SCV2无处不在动物的胰腺来建模和了解SARS-COV2感染如何影响β细胞的存活，代谢和功能。有争议在有关SARS-COV2是否直接感染β细胞并影响β细胞功能和生存或生存或的文献中如果患者中葡萄糖稳态的破坏是继发性的。我们假设SARS-COV2感染直接而急性地损害了β细胞功能和生存，通过重编程细胞代谢，因此，在感染期间或之后，离开宿主容易受到糖尿病的影响。这些高度创新的实验利用独特且与临床相关的模型系统和员工尖端技术来评估如何评估 β细胞存活和代谢受SARS-COV2感染的影响。这些实验将提供关键急性高血糖，糖尿病的新兴临床表型基础的机械洞察力酮症酸中毒以及可能影响大量患者的终身糖尿病从Covid19恢复。该提议的目的是保护PI提供文化意识的时间对来自历史上代表性不足的背景的研究生进行指导和深入培训参加这项创新研究计划。这个目标与PI的直接和长期相吻合目标是：（1）建立商品（在LOS儿童医院指导新兴的研究人员 Angeles）作为CHLA教育和研究基础设施的基本组成部分，（2）纵向跟踪和量化商品LA毕业生的成果，分为与生物科学相关的研究生职业。