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. As initial steps in this project, we plan to establish 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 intend to initiate 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011153-01
Application #
7966121
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2009
Total Cost
$248,874
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Linehan, Jonathan L; Harrison, Oliver J; Han, Seong-Ji et al. (2018) Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair. Cell 172:784-796.e18
Sui, Yongjun; Dzutsev, Amiran; Venzon, David et al. (2018) Influence of gut microbiome on mucosal immune activation and SHIV viral transmission in naive macaques. Mucosal Immunol 11:1219-1229
Vetizou, Marie; Trinchieri, Giorgio (2018) Anti-PD1 in the wonder-gut-land. Cell Res 28:263-264
Trinchieri, Giorgio (2018) Natural Killer Cells Detect a Tumor-Produced Growth Factor: A Vestige of Antiviral Resistance? Trends Immunol 39:357-358
Dutzan, Nicolas; Abusleme, Loreto; Bridgeman, Hayley et al. (2017) On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier. Immunity 46:133-147
Dzutsev, Amiran; Badger, Jonathan H; Perez-Chanona, Ernesto et al. (2017) Microbes and Cancer. Annu Rev Immunol 35:199-228
Stroncek, David F; Butterfield, Lisa H; Cannarile, Michael A et al. (2017) Systematic evaluation of immune regulation and modulation. J Immunother Cancer 5:21
Rosshart, Stephan P; Vassallo, Brian G; Angeletti, Davide et al. (2017) Wild Mouse Gut Microbiota Promotes Host Fitness and Improves Disease Resistance. Cell 171:1015-1028.e13
Roy, Soumen; Trinchieri, Giorgio (2017) Microbiota: a key orchestrator of cancer therapy. Nat Rev Cancer 17:271-285
Namasivayam, Sivaranjani; Maiga, Mamoudou; Yuan, Wuxing et al. (2017) Longitudinal profiling reveals a persistent intestinal dysbiosis triggered by conventional anti-tuberculosis therapy. Microbiome 5:71

Showing the most recent 10 out of 37 publications