Biology subjects

Schmidt, E. E.

Publications and source records attributed to Schmidt, E. E..

2 recordsLinked to original sources

bioRxiv2025

Primary bovine embryonic fibroblasts support seasonal influenza A virus infection and demonstrate variable fitness of HPAI H5N1

The emergence of highly pathogenic avian influenza (HPAI) H5N1 (clade 2.3.4.4b, genotype B3.13) in dairy cattle presents substantial challenges to the agricultural sector and public health. Mechanistic studies of infection and transmission in cattle have proven difficult due to animal handling restrictions as well as limited availability of established cell culture models. Primary Bovine Embryonic Fibroblasts (BeEFs) were collected from a Montana cow and are investigated here as a model to study influenza A virus (IAV) infection dynamics. We compared sialylation profiles, infectious virus production, viral replication, and plaque morphology in both BeEFs and chicken DF-1 cells following infection with the bovine HPAI H5N1 and an earlier 2.3.4.4b genotype (B1.1) isolated in 2022. The data presented here show increased viral fitness of the bovine origin HPAI H5N1 strains across multiple species and bovine susceptibility to human seasonal IAV. This study highlights the ability of BeEFs to serve as a model for studying IAV infections in bovine hosts.

microbiology↗

bioRxiv2022

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation and Progression

Mutations in the KEAP1-NRF2 pathway occur in up to a third of non-small cell lung cancer (NSCLC) cases and often confer resistance to therapy and poor outcomes. Here, we developed murine alleles of the KEAP1 and NRF2 mutations found in human NSCLC and comprehensively interrogated their impact on tumor initiation and progression. Chronic Nrf2 stabilization by Keap1 or Nrf2 mutation was not sufficient to induce tumorigenesis, even in the absence of tumor suppressors p53 or Lkb1. When combined with KrasG12D/+, constitutive Nrf2 activation promoted lung tumor initiation and early progression of hyperplasia to low-grade tumors but impaired their progression to advanced-grade tumors, which was reversed by Nrf2 deletion. Finally, NRF2 overexpression in KEAP1 mutant NSCLC cell lines was detrimental to cell proliferation, viability, and anchorage-independent colony formation. Collectively, our results establish the context-dependence and activity threshold for NRF2 during the lung tumorigenic process. SignificanceThis study reports murine lung cancer models harboring mutations in the Keap1/Nrf2 pathway and highlights the context-dependent and diverse roles of Nrf2 during lung tumor initiation and progression.

cancer biology↗