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You are here: Home Administration Chemistry & Biochemistry Department Events Archives 2018 April Biochemistry Seminar: Matthew Redinbo, "Treating Disease by Drugging the Gut Microbiome"

Biochemistry Seminar: Matthew Redinbo, "Treating Disease by Drugging the Gut Microbiome"

Matthew Redinbo, William R. Kenan Distinguished Professor, Chem, Biochem, Microbiology & Genomics, Univ of North Carolina at Chapel Hill, "Treating Disease by Drugging the Gut Microbiome"
When Apr 18, 2018
from 12:00 PM to 01:00 PM
Where CUNY ASRC Main Auditorium
Contact Name
Contact Phone 212-650-8803
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The diverse and complex communities of GI microbiota play important roles in human health.  We focused on systems where the bacteria catalyze a reaction that exerts a profoundly negative impact on intestinal tissues.  The anticancer drug irinotecan is used to treat colon and pancreatic cancers, and is eliminated as an inactivated drug-glucuronide by the Phase II drug-metabolism.  Irinotecan's dose-limiting toxicity is severe delayed diarrhea hypothesized to arise from the reactivation of the inactive irinotecan metabolite in the gut.  We pinpointed the molecular basis of this reactivation to the beta-glucuronidase sugar scavenging enzymes present in gut bacteria.  We further developed potent, selective and non-lethal inhibitors to bacterial beta-glucuronidase (GUS) enzymes and demonstrated that they prevented GI injury in mouse models of irinotecan-induced intestinal damage.   Bacterial GUS inhibitors prevent these sites of intestinal damage in mice treated with NSAIDs, which are also glucuronidated.  Our data demonstrate that enzyme targets in the GI microbiota can be inhibited to improve human health.  Furthermore, our results shed significant light on the mammalian-microbial axes of chemical communication on-going between two domains of life in the “higher-order” human superorganism.


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