Saturday, November 23, 2024
11/23/2024
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.
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