Student Theses and Dissertations
Date of Award
2025
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
Thesis Advisor
Sean F. Brady
Keywords
Fusobacteria, inflammation, cancer, nuclear factor signaling, ADP-heptose, ribonucleotides
Abstract
Colonization by Fusobacteria is associated with diverse inflammatory diseases and cancers, but the underlying molecular mechanisms that drive these associations remain elusive. Here I report studies showing that among commensal bacteria, Fusobacteria are uniquely potent activators of nuclear factor kappa B (NF-κB) signaling, a pathway implicated in inflammatory diseases and cancers. I found that Fusobacterium nucleatum secretes pathogen-associated molecular pattern ADP-heptose and ribonucleotides that together, but not individually, strongly induced NF-κB signaling as well as the expression of inflammation and cancer associated genes. This finding suggests a regulatory role for extracellular nucleotides in ADP-heptose detection, and also provides a potentially key mechanism for Fusobacteria's diverse disease associations. In addition, the results of these studies suggest that inhibiting the accumulation of either metabolite could prove therapeutically useful.
DOI
10.48496/ptmh-gh90
License and Reuse Information
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
Ye, Linzhi, "ADP-Heptose and Nucleotide Enhancers Drive Fusobacteria-Induced Inflammation" (2025). Student Theses and Dissertations. 831.
https://doi.org/10.48496/ptmh-gh90
Comments
A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy