Mentoring Emerging Researchers at CHLA (MERCH-LA)

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基础。 有临床和分子证据表明，COVID 19的发病机制可能具有急性和特异性， 对胰腺β细胞功能的影响理解SARS-CoV 2感染如何 影响患者β细胞功能和存活的生理相关动物模型数量有限 学习我们利用SCV 2接种动物胰腺的独特途径进行建模， 了解SARS-CoV 2感染如何影响β细胞的存活、代谢和功能。存在争议 在关于SARS-COV 2是否直接感染β细胞并影响β细胞功能和存活的文献中， 如果患者体内葡萄糖稳态的破坏是继发性的。我们假设SARS-CoV 2感染 通过重编程细胞代谢直接和急性损害β细胞功能和存活， 从而使宿主在感染期间或之后易患糖尿病。这些高度创新的实验 利用一个独特的和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-CoV 2感染的影响。这些实验将提供关键的 对急性高血糖症、糖尿病性高血糖症、糖尿病性高血糖症和糖尿病性高血糖症的新出现的临床表型的基础的机制性洞察， 酮症酸中毒和潜在的终身糖尿病，可能会影响大量患有糖尿病的患者， 从COVID 19中恢复过来。这项建议的目的是保护PI的时间，以提供文化意识， 为来自历史上代表性不足背景的研究生提供指导和强化培训 参与这项创新的研究计划。这一目标与PI的短期和长期目标相吻合 目标是：（1）建立MERCH-LA（洛杉矶儿童医院新兴研究人员指导） 洛杉矶）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MERCH-LA毕业生进入生物科学相关研究生职业的结果。

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.