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.
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://digitalcommons.rockefeller.edu/student_theses_and_dissertations/831
Comments
A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy