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.

项目概要 β 细胞功能障碍和死亡是 2 型糖尿病发展的重要病理基础。临床和分子证据表明，COVID19 的发病机制可能具有急性和特异性。对胰腺 β 细胞功能的影响是理解 SARS-CoV2 感染如何可能的障碍之一。影响患者β细胞功能和生存的是生理相关动物模型数量有限我们利用 SCV2 接种动物的胰腺的独特途径来进行建模和研究。了解 SARS-CoV2 感染如何影响 β 细胞的存活、代谢和功能尚存在争议。文献中关于 SARS-COV2 是否直接感染 β 细胞并影响 β 细胞功能和存活或如果患者体内葡萄糖稳态的破坏是继发性的，那么我们发现 SARS-CoV2 感染是继发性的。通过重新编程细胞代谢，直接而严重地损害 β 细胞功能和生存，从而使宿主在感染期间或之后容易患糖尿病。这些高度创新的实验。利用独特且临床相关的模型系统，并采用尖端技术来评估如何 β 细胞的存活和代谢受到 SARS-CoV2 感染的影响，这些实验将提供关键的证据。对急性高血糖、糖尿病等新兴临床表型基础的机制洞察酮症酸中毒和潜在的终生糖尿病可能会影响大量患有糖尿病的患者该提案的目的是保护 PI 提供文化意识的时间。对历史上代表性不足的背景的研究生进行指导和强化培训参与这一创新研究计划与 PI 的近期和长期目标相吻合。目标是：(1) 建立 MERCH-LA（指导洛杉矶儿童医院的新兴研究人员）安吉利斯）作为 CHLA 教育和研究基础设施的基本组成部分，以及 (2) 纵向跟踪和量化 MERCH-LA 毕业生进入生物科学相关研究生职业的成果。