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.
","abstract_html":"<p>Colonization by <em>Fusobacteria</em> 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, <em>Fusobacteria</em> are uniquely potent activators of nuclear factor kappa B (NF-κB) signaling, a pathway implicated in inflammatory diseases and cancers. I found that <em>Fusobacterium</em> <em>nucleatum</em> secretes pathogen-associated molecular pattern ADP-heptose and ribonucleotides that together, but not individually, strongly induced NF-<em>κ</em>B 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 <em>Fusobacteria's</em> diverse disease associations. In addition, the results of these studies suggest that inhibiting the accumulation of either metabolite could prove therapeutically useful.<em></em></p>","abstract_has_math":false,"creators":["Ye, Linzhi"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Sean F. Brady"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-01-01T08:00:00Z","date_published":"2025-01-01T08:00:00Z","updated_at":"2026-07-24T04:11:21Z","subjects":["Fusobacteria","inflammation","cancer","nuclear factor signaling","ADP-heptose","ribonucleotides","Life Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/831","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Sean F. Brady"]},{"key":"dc:creator","label":"Author","values":["Ye, Linzhi"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2027-03-11T08:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Fusobacteria","inflammation","cancer","nuclear factor signaling","ADP-heptose","ribonucleotides","Life Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/831"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["ADP-Heptose and Nucleotide Enhancers Drive Fusobacteria-Induced Inflammation"]}]}],"canonical_facts":{"dc:contributor":["Sean F. Brady"],"dc:creator":["Ye, Linzhi"],"dc:date.available":["2027-03-11T08:00:00Z"],"dc:description.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.
"],"dc:identifier":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/831"],"dc:subject":["Fusobacteria","inflammation","cancer","nuclear factor signaling","ADP-heptose","ribonucleotides","Life Sciences"],"dc:title":["ADP-Heptose and Nucleotide Enhancers Drive Fusobacteria-Induced Inflammation"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T04:11:21Z"}