Yuning Chen
Profile Url: yuning-chen
Researcher at Department of Biostatistics, Boston University School of Public Health
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Metabolic dysregulation in multiple tissues alters glucose homeostasis and influences risk for type 2 diabetes (T2D). To identify pathways and tissues influencing T2D-relevant glycemic traits (fasting glucose [FG], fasting insulin [FI], two-hour glucose [2hGlu] and glycated hemoglobin [HbA1c]), we investigated associations of exome-array variants in up to 144,060 individuals without diabetes of multiple ancestries. Single-variant analyses identified novel associations at 21 coding variants in 18 novel loci, whilst gene-based tests revealed signals at two genes, TF (HbA1c) and G6PC (FG, FI). Pathway and tissue enrichment analyses of trait-associated transcripts confirmed the importance of liver and kidney for FI and pancreatic islets for FG regulation, implicated adipose tissue in FI and the gut in 2hGlu, and suggested a role for the non-endocrine pancreas in glucose homeostasis. Functional studies demonstrated that a novel FG/FI association at the liver-enriched G6PC transcript was driven by multiple rare loss-of-function variants. The FG/HbA1c-associated, islet-specific G6PC2 transcript also contained multiple rare functional variants, including two alleles within the same codon with divergent effects on glucose levels. Our findings highlight the value of integrating genomic and functional data to maximize biological inference.
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Coronaviruses have caused three major outbreaks of infectious disease since the beginning of 21st century. Broad-spectrum strategies that can be utilized in both current and future coronavirus outbreaks and mutation-tolerant are sought after. Here we report a monoclonal antibody 3E8 targeting human angiotensin-converting enzyme 2 (ACE2) neutralized pseudo-typed coronaviruse SARS-CoV-2, SARS-CoV-2-D614G, SARS-CoV and HCoV-NL63, without affecting physiological activities of ACE2 or causing toxicity in mouse model. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a mouse model of COVID-19. Cryo-EM studies revealed the binding site of 3E8 on ACE2 and identified Histone 34 of ACE2 as a critical site of anti-viral epitope. Overall, our work has provided a potential pan coronavirus management strategy and disclosed a pan anti-coronavirus epitope on human ACE2 for the first time. ### Competing Interest Statement Yi-Li Chen, Ganjun Chen and Chunhe Wang are employed by Dartsbio Pharmaceuticals