# Metallothionein 1E as a Central Regulator of Human Pancreatic Beta Cell Function and Survival > **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $397,733 ## Abstract Abstract. COVID-19 was declared a pandemic by the World Health Organization. COVID19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the coronaviridae, a diverse family of viruses that cause a range of diseases in humans and animals. Recent clinical studies show a strong association with COVID-19 and diabetes. Additional studies suggest that diabetes is not only a risk factor for severe COVID- 19 disease but also that SARS-CoV-2 infection can induce a new onset diabetes. However, it is not clear what diabetes-associated cells are infected by the virus and how these cells respond to SARS-CoV-2 infection. A number of studies support the hypothesis that viral infections play a causative role in Type 1 diabetes (T1D). Enterovirus isolates obtained from newly diagnosed T1D patients can infect and destroy human islet cells in vitro. In T1D patients, beta cell mass decreases due to auto-immune destruction. Here, we assemble a multi- disciplinary investigator team, including expert beta cell biologist (Dr. Chen), stem cell biologists (Drs. Evans and Schwartz), and a virologist (Dr. tenOever) to systematically study the impact of SARS-CoV-2 on pancreatic endocrine cells and test the hypothesis that SARS-CoV-2 infection causes human pancreatic endocrine cell destruction. In preliminary studies, we found that human pluripotent stem cell (hPSC)-derived pancreatic endocrine cells are permissive to SARS-CoV-2 infection, which was further validated using adult primary human islets. Transcript profiling following SARS-CoV-2 infection of hPSC-derived pancreatic endocrine cells revealed striking upregulation of chemokines, similar to profiles of tissues obtained after autopsy of COVID-19 patients. In addition, we performed two high content chemical screens and identified several FDA-approved drugs that show anti-SARS-CoV-2 activities on both hPSC-derived colonic and lung organoids. Here, we propose to validate the SARS-CoV-2 infection using pancreatic samples from COVID-19 patients, examine the impact of SARS-CoV-2 infection on human endocrine cells, and re-purpose FDA-approved drugs to protect human pancreatic endocrine cells from SRAS-CoV-2 infection. Three aims are proposed: Aim 1. Validate SARS-CoV-2 infection in pancreatic samples from post-mortem COVID-19 patients. Aim 2. Examine the impact of SARS-CoV-2 infection on human pancreatic endocrine cell function and survival. Aim 3. Repurpose FDA-approved drugs to protect human pancreatic endocrine cells from SARS-CoV-2 infection. Through this study, we expect to provide direct pathogenic evidence of SARS-CoV-2 infection of human pancreatic endocrine cells, understand the pathogenesis of SARS-CoV-2 infected pancreatic endocrine cells, and develop novel approaches to protect human endocrine cells from SARS-CoV-2 infection. ## Key facts - **NIH application ID:** 10220173 - **Project number:** 3R01DK119667-02S1 - **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV - **Principal Investigator:** Shuibing Chen - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $397,733 - **Award type:** 3 - **Project period:** 2019-07-01 → 2023-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10220173 ## Citation > US National Institutes of Health, RePORTER application 10220173, Metallothionein 1E as a Central Regulator of Human Pancreatic Beta Cell Function and Survival (3R01DK119667-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10220173. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*