Abstract

It is a central theme of this Program Project that inflammation causes cancer. We strive to understand how it causes cancer, particularly cancers of the gastrointestinal tract, because understanding the chemical and molecular steps underlying the mechanism of neoplastic transformation provides valuable insight into the biology of end stage cancers. Moreover, this mechanistic understanding identifies steps at which intervention in terms of therapy or prevention strategies is likely to reduce disease burden in humans. Project 2 integrates with Project 1, which identifies a population of chemical mediators that in aggregate represent the drivers of the genetic changes many researchers believe underpin the conversion of normal cells into cancer cells. These

Public Health Relevance

This Project utilizes unique chemical and genetic tools to uncover the type, amount and genetic requirements for the inflammation-induced local mutations and DNA strand breaks that presumably initiate and help drive the process of carcinogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA026731-35A1
Application #
8666941
Study Section
Special Emphasis Panel (ZCA1-RPRB-B (J1))
Project Start
1997-01-15
Project End
2019-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
35
Fiscal Year
2014
Total Cost
$186,571
Indirect Cost
$66,974

  Institution

Name
Massachusetts Institute of Technology
Department
Type
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02142

  Publications

Gu, Chen; Ramos, Jillian; Begley, Ulrike et al. (2018) Phosphorylation of human TRM9L integrates multiple stress-signaling pathways for tumor growth suppression. Sci Adv 4:eaas9184
Wadduwage, Dushan N; Kay, Jennifer; Singh, Vijay Raj et al. (2018) Automated fluorescence intensity and gradient analysis enables detection of rare fluorescent mutant cells deep within the tissue of RaDR mice. Sci Rep 8:12108
Tajai, Preechaya; Fedeles, Bogdan I; Suriyo, Tawit et al. (2018) An engineered cell line lacking OGG1 and MUTYH glycosylases implicates the accumulation of genomic 8-oxoguanine as the basis for paraquat mutagenicity. Free Radic Biol Med 116:64-72
Rothenberg, Daniel A; Taliaferro, J Matthew; Huber, Sabrina M et al. (2018) A Proteomics Approach to Profiling the Temporal Translational Response to Stress and Growth. iScience 9:367-381
Wang, Xin; Garcia, Carlos T; Gong, Guanyu et al. (2018) Automated Online Solid-Phase Derivatization for Sensitive Quantification of Endogenous S-Nitrosoglutathione and Rapid Capture of Other Low-Molecular-Mass S-Nitrosothiols. Anal Chem 90:1967-1975
Chan, Cheryl; Pham, Phuong; Dedon, Peter C et al. (2018) Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses. Genome Biol 19:228
Fedeles, Bogdan I (2017) G-quadruplex-forming promoter sequences enable transcriptional activation in response to oxidative stress. Proc Natl Acad Sci U S A 114:2788-2790
Townsend, Todd A; Parrish, Marcus C; Engelward, Bevin P et al. (2017) The development and validation of EpiComet-Chip, a modified high-throughput comet assay for the assessment of DNA methylation status. Environ Mol Mutagen 58:508-521
Kimoto, Takafumi; Kay, Jennifer E; Li, Na et al. (2017) Recombinant cells in the lung increase with age via de novo recombination events and clonal expansion. Environ Mol Mutagen 58:135-145
Edrissi, Bahar; Taghizadeh, Koli; Moeller, Benjamin C et al. (2017) N6-Formyllysine as a Biomarker of Formaldehyde Exposure: Formation and Loss of N6-Formyllysine in Nasal Epithelium in Long-Term, Low-Dose Inhalation Studies in Rats. Chem Res Toxicol 30:1572-1576

Showing the most recent 10 out of 361 publications