In the Section of Cancer Immmunobiology as well as in a few other Sections within the Cancer and Inflammation Program as well as other part of CCR there is great need to understand the role of the gut flora in the pathogenesis of inflammatory and immune colitis and in mouse models of colitis-associated cancer. We extensively use mice deficient for immune or inflammation-related genes and it is always difficult to distinguish a direct effect of those genes on the colitis or cancer, or an indirect one through the regulation of the intestinal flora. Other collaborative studies in the program are directed to the study of the role of the liver immune response in controlling liver carcinogenesis and it is likely that the inflammatory-immunological microenvironment in the liver is also significantly affected by the composition of the intestinal flora. Overall these studies would greatly benefit by the access to a germ free facility and particularly by the availability of committed expertise in gut microbiology based on state of the art sequencing and bioinformatics, expertise that it is of difficult access to single laboratories but that could be efficiently provided to a multidisciplinary extended consortium of laboratories with overlapping interests in this field.We have established methods for the determination of mouse microbioma using 454 sequencing of 16 RNA, cytofluorimetric analysis of FISH labeling of specific bacterial types, and possibly other approaches including microarray. Sequencing and bioinformatic expertise will be needed. We also initiated studies with germ free mice, gnotobiotic mice with defined intestinal flora, and mice reconstitute after antibiotic treatment. Initially we plan to study the role of the intestinal flora in experimental models of colitis and colitis-associated cancer using mice genetically deficient for inflammation-controlling genes such as MyD88, IL-18, TNF, TLRs, and others. The role of commensal microbiota in energetic alteration associated with cancer (i.e. obesiti, cachxia, anorexia) is being planned in murine experimental models and in observational clinical experimentation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011153-04
Application #
8553005
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2012
Total Cost
$731,778
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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Dzutsev, Amiran; Trinchieri, Giorgio (2015) Proteus mirabilis: The Enemy Within. Immunity 42:602-4
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Swiecki, Melissa; Wang, Yaming; Riboldi, Elena et al. (2014) Cell depletion in mice that express diphtheria toxin receptor under the control of SiglecH encompasses more than plasmacytoid dendritic cells. J Immunol 192:4409-16
Viaud, Sophie; Daillere, Romain; Yamazaki, Takahiro et al. (2014) Why should we need the gut microbiota to respond to cancer therapies? Oncoimmunology 3:e27574

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