Biology subjects

French, E.

Publications and source records attributed to French, E..

3 recordsLinked to original sources

bioRxiv2024

Molecular Magnetic Resonance Imaging of Dysregulated Zinc Secretion Detects Early Pancreatic Ductal Adenocarcinoma Lesions and Response to KRASG12D Inhibitor Treatment

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, primarily due to late-stage diagnosis and limited treatment options. Zinc homeostasis is markedly dysregulated in PDAC and this dysregulation can be probed by administering a secretagogue to stimulate zinc secretion (SSZS) in the exocrine pancreas and imaging this secretion with a zinc sensitive MRI probe. This study demonstrates the potential of SSZS MRI for early detection, monitoring treatment response, and assessing recurrence after treatment withdrawal in PDAC. Our approach relies on interrogating the pancreas, circumventing the challenge of locating small, elusive tumors. By SSZS MRI, we detected PDAC by observing the unique zinc hypersecretory activity of the pancreas when malignancy is present. We observed dysregulation of zinc transporters in both human and mouse pancreas containing PDAC and confirmed secretagogue-stimulated zinc secretion in vitro and in vivo. We found that combining secretagogues such as secretin and caerulein maximized zinc secretion and as such MRI signal in the pancreas. Notably, SSZS MRI detected treatment responses to KRAS G12D inhibition within 3-5 days and identified cancer recurrence as early as one day post-treatment withdrawal. Additionally, secretagogue stimulation improved treatment responses and delayed recurrence in both treatment models. These findings suggest that SSZS MRI could significantly enhance PDAC diagnosis and management, providing a novel, non-invasive imaging modality to improve patient outcomes. STATEMENT OF SIGNIFICANCEThis study demonstrates the utility of secretagogue-stimulated zinc secretion (SSZS) MRI in detecting pancreatic ductal adenocarcinoma (PDAC) at early stages, monitoring treatment responses, and assessing cancer recurrence, thereby offering a promising non-invasive imaging modality to improve PDAC patient management and outcomes.

cancer biology↗

bioRxiv2019

Defense hormones modulate root microbiome diversity and composition in tomato

Plant roots live closely associated with soil microbes. Understanding how roots defend against pathogenic microbes while associating with non-pathogenic microbes is critical to using root microbiomes for successful outcomes. The aim of this study was to determine the contribution of the plant defense hormones ethylene (ET), jasmonic acid (JA), and salicylic acid (SA) to the tomato root microbiome. We used 16S rRNA amplicon sequencing to examine the root microbiome of four tomato genotypes defective in three hormone pathways. We found that ET and SA pathways, but not JA, were critical for root endosphere microbial alpha ()-diversity. Root endosphere communities of ACD, deficient in a precursor of ET, and the SA-deficient NahG transgenic, had significantly less -diversity than wild-type tomatoes. NahG and ACD root endosphere enrichment profiles were similar and driven by two taxa. In NahG, ACD, and in a panel of 24 wild-type tomatoes, the abundance of these two taxa was correlated with lower root endosphere -diversity. The abundance of these taxa was also moderately negatively correlated with the level of SA in roots. Our results suggest that SA and ET pathways contribute to tomato root endosphere diversity by modulating the abundance of specific bacterial taxa.

plant biology↗

bioRxiv2017

Whole Root Transcriptomic Analysis Reveals a Role for Auxin Pathways in Resistance to Ralstonia solanacearum in Tomato

The soilborne pathogen Ralstonia solanacearum is the causal agent of bacterial wilt, and causes significant crop loss in the Solanaceae family. The pathogen first infects roots, which are a critical source of resistance in tomato (Solanum lycopersicum L.). Roots of both resistant and susceptible plants are colonized by the pathogen, yet rootstocks can provide significant levels of resistance. Currently, mechanisms of this root-mediated resistance remain largely unknown. To identify the molecular basis of this resistance, we analyzed the genome-wide transcriptional response of roots of resistant (Hawaii 7996) and susceptible (West Virginia700) tomatoes at multiple time points after inoculation with R. solanacearum. We found that defense pathways in roots of the resistant Hawaii7996 are activated earlier and more strongly than roots of susceptible West Virginia700. Further, auxin signaling and transport pathways are suppressed in roots of the resistant variety. Functional analysis of an auxin transport mutant in tomato confirmed a role for auxin pathways in bacterial wilt. Together, our results suggest that roots mediate resistance to R. solanacearum through genome-wide transcriptomic changes that result in strong activation of defense genes and alteration of auxin pathways.

plant biology↗