Biology subjects

Pennington, S.

Publications and source records attributed to Pennington, S..

3 recordsLinked to original sources

bioRxiv2026

Microphysiological Flow Batteries For Dynamic EDC Screening Of mESC-derived Thyroid Organoids

Endocrine disrupting chemicals (EDCs) are ubiquitous environmental contaminants capable of dysregulating the production of thyroid hormones. Traditional thyroid toxicological assays rely on 2D cell cultures and animal models, both of which fail to accurately recapitulate human thyroid physiology and provide limited mechanistic insight into EDC toxicity. To overcome these limitations, we report a novel thyroid-on-chip platform integrating mouse embryonic stem cell-derived thyroid organoids with advanced organ-on-chip (OoC) technology and downstream multi-omics analysis. The platform leverages a reversibly-sealed microphysiological flow battery (MFB) to allow scale up of dynamic organoid culture and controlled chemical exposure while reducing operational complexity. Upon EDC exposure, transcriptomic and proteomic analysis revealed new molecular signatures of thyroid disruption across four different EDC classes, even at very low EDC concentrations (1nM), validating the capacity of this system to mechanistically dissect EDC-induced responses. This represents an integrated platform consists of an advanced physiologically relevant assay framework for next-generation endocrine toxicity testing, bridging the gap between in vitro screening and in vivo thyroid physiology.

bioengineering↗

bioRxiv2025

Experimental flooding impacts soil biogeochemistry but not aboveground vegetation in a coastal forest

Rising sea levels and intensifying storms increase flooding pressure on coastal forests, triggering tree mortality, ecosystem transitions, and changes to the coastal carbon cycle. However, the mechanisms that drive coastal forest mortality remain elusive due to the complex interplay between belowground and aboveground processes during flooding disturbances and limitations of observations typically reported in coastal forest mortality studies. We used an ecosystem-scale manipulation to simulate hurricane-level flooding of a coastal forest. Monitoring real-time soil conditions and tree physiological responses, we observed consistent impacts on soil biogeochemistry aligned with belowground drivers of tree mortality, but no consistent responses in aboveground vegetation. Our findings provide unprecedented empirically based insight into the earliest stages of a hypothesized forest mortality spiral and offer critical benchmarks for predicting coastal forest resilience in the face of accelerating climate change. Significance StatementChanging sea levels and storms are causing more flooding in coastal forests. This flooding kills trees, changing how coastal ecosystems function, but we do not fully understand what factors determine whether forests survive flooding. We designed an ecosystem-scale experiment to answer this question, with controlled saltwater and freshwater floods equivalent to a hurricane in experimental forest plots. Flooding quickly changed soil conditions, but we have not yet observed consistent tree stress responses. Our study provides the most detailed measurements to date of how coastal forests respond to flooding in real time. These findings will help us better understand the early mechanisms and warning signs of forests threatened by flooding.

systems biology↗

bioRxiv2020

Sequential infection with influenza A virus followed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to more severe disease and encephalitis in a mouse model of COVID-19.

COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2, a recently emerged coronavirus that rapidly caused a pandemic. Coalescence of this virus with seasonal respiratory viruses, particularly influenza virus is a global health concern. To investigate this, transgenic mice expressing the human ACE2 receptor driven by the epithelial cell cytokeratin-18 gene promoter (K18-hACE2) were first infected with IAV followed by SARS-CoV-2. The host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 only. Infection of mice with each individual virus resulted in a disease phenotype compared to control mice. Although SARS-CoV-2 RNA synthesis appeared significantly reduced in the sequentially infected mice, they exhibited more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to singly infected or control mice. The sequential infection also exacerbated the extrapulmonary encephalitic manifestations associated with SARS-CoV-2 infection. Conversely, prior infection with a commercially available, multivalent live-attenuated influenza vaccine (Fluenz tetra) elicited the same reduction in SARS-CoV-2 RNA synthesis albeit without the associated increase in disease severity. This suggests that the innate immune response stimulated by infection with IAV is responsible for the observed inhibition of SARS-CoV-2, however, infection with attenuated, apathogenic influenza vaccine does not result in an aberrant immune response and enhanced disease severity. Taken together, the data suggest that the concept of twinfection is deleterious and mitigation steps should be instituted as part of a comprehensive public health response to the COVID-19 pandemic.

microbiology↗