Biology subjects

Moore, E. E.

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

3 recordsLinked to original sources

bioRxiv2026

Rethinking Syndecan-1 as a Marker of Trauma-Induced Endothelial Injury

Syndecan-1 (SDC1), a transmembrane proteoglycan and component of the glycocalyx, is widely considered the key circulating biomarker of endothelial dysfunction in trauma and critical illness. However, the tissue distribution of SDC1 and the cellular origin of plasma SDC1 in health and disease are incompletely understood. This series of experiments integrates immunostaining, spatial transcriptomics (GeoMx Digital Spatial Profiler (DSP) and Xenium), and single-cell atlases to map SDC1, as well as the other three members of the syndecan family, syndecan-2 (SDC2), syndecan-3 (SDC3), and syndecan-4 (SDC4), across mouse and human tissues, including the lung, gastrointestinal tract, and brain. Across modalities, SDC1 primarily localizes to epithelial compartments, as demonstrated by colocalization with epithelial markers and enrichment in epithelial cell types in the lung and gut. Spatial profiling further identifies SDC1 and SDC4 enrichment in airway epithelial niches, SDC3 in endothelial-rich regions, and SDC2 distributed more broadly across compartments. Mouse and human single-cell atlases confirm epithelial predominance of SDC1. These findings define the cellular and spatial landscape of syndecan expression in healthy tissues and support SDC1 as an epithelial-enriched proteoglycan. These results also challenge the specificity of circulating SDC1 as a biomarker of endotheliopathy and raise the possibility that epithelial injury contributes substantially to circulating SDC1 after trauma and critical illness.

cell biology↗

bioRxiv2023

Trans-Omics analysis of post injury thrombo-inflammation identifies endotypes and trajectories in trauma patients.

Understanding and managing the complexity of trauma-induced thrombo-inflammation necessitates an innovative, data-driven approach. This study leveraged a trans-omics analysis of longitudinal samples from trauma patients to illuminate molecular endotypes and trajectories that underpin patient outcomes. We hypothesized that trans-omics profiling reveals underlying clinical differences in severely injured patients that may present with similar clinical characteristics but ultimately have different responses to treatment and outcomes. Here we used proteomics and metabolomics to profile 759 of longitudinal plasma samples from 118 patients at 11 time points and 97 control subjects. Patients were stratified by shock and injury severity, revealing a spectrum of responses to trauma and treatment that are fundamentally tied to their unique underlying biology. Ensemble models were employed, demonstrating the predictive power of these molecular signatures with area under the receiver operating curves of 80 to 94% for key outcomes such as death. Then, transomics-based patient states were defined to create a map of unique pathophysiologic states encountered by trauma patients across time. Last, distinct longitudinal patient trajectories were identified that group patients according to their path through trauma transomics state maps. Unsupervised clustering of longitudinal trans-omics data identified specific clinical phenotypes while omics-based trajectories increased resolution on outcome prediction. The molecularly defined endotypes and trajectories provide an unprecedented lens to understand and potentially guide trauma patient management, opening a path towards precision medicine. This strategy presents a transformative framework that aligns with our understanding that trauma patients, despite similar clinical presentations, might harbor vastly different biological responses and outcomes. One-sentence summaryTransomic analyses of longitudinal plasma samples from severely injured patients identifies endotypes and trajectories that predict clinical outcomes.

biochemistry↗

bioRxiv2020

Free-water metrics in medial temporal lobe white matter tract projections relate to longitudinal cognitive decline

ObjectiveHippocampal volume is a sensitive marker of neurodegeneration and a well-established predictor of age-related cognitive impairment. Recently, free-water (FW) magnetic resonance imaging (MRI) has shown associations with pathology in Alzheimers disease (AD), but it is still unclear whether these metrics are associated with measures of cognitive impairment. Here, we investigate whether FW and FW-corrected fractional anisotropy (FAT) within medial temporal lobe white matter tracts (cingulum, fornix, uncinate fasciculus, inferior longitudinal fasciculus, and tapetum) provides meaningful contribution to cognition and cognitive decline beyond hippocampal volume. Participants and MethodsVanderbilt Memory & Aging Project participants (n=319, 73{+/-}7 years, 59% male) with normal cognition and mild cognitive impairment (40% of cohort) underwent baseline brain MRI, including structural MRI to quantify hippocampal volume, diffusion MRI to quantify medial temporal lobe white matter tract FW and FAT, and longitudinal neuropsychological assessment with a mean follow-up of 3.5 years. Linear regressions were conducted to determine how hippocampal volume and white matter tract FW and FAT interact with baseline memory and executive function performances. Competitive model analyses determined the unique variance provided by white matter tract FW and FAT beyond that of hippocampal volume and other comorbidities. Linear mixed-effects models were conducted to determine how baseline hippocampal volume and white matter tract FW and FAT interact to explain longitudinal change in memory and executive function performances. ResultsFW in the inferior longitudinal fasciculus, tapetum, uncinate fasciculus, and cingulum were robustly associated with baseline memory and executive function. Further, competitive model analysis showed that tract FW contributed unique variance beyond other comorbidities and hippocampal volume for memory ({Delta}Radj2 range: 0.82-2.00%) and executive function ({Delta}Radj2 range: 0.88-1.87%). Longitudinal analyses demonstrated significant interactions of hippocampal volume and FAT in the inferior longitudinal fasciculus (p=0.02), tapetum (p=0.02), uncinate fasciculus (p=0.02), and cingulum (p=0.002) with decline in memory. For decline in executive function, we found significant interactions of hippocampal volume and FAT in inferior longitudinal fasciculus (p=0.03), tapetum (p=0.02), uncinate fasciculus (p=0.02), and fornix (p=0.02), as well as cingulum (p=0.02) and fornix (p=0.02) FW. ConclusionsOur results highlight novel associations between FW and FAT measures of medial temporal lobe tract microstructure and cognitive performance such that individuals with smaller hippocampal volumes and lower tract microstructure experience greater cognitive decline. These results suggest that white matter has a unique role in cognitive decline and, therefore, could be used to provide better disease staging, allowing for more precise disease monitoring in AD.

neuroscience↗