Abstract

We have explored transcriptional patterns associated with spontaneous cancer development and chemically-induced carcinogenesis. In these studies, it is necessary to control mixed directional false discovery rate due to the fact that we tested for multiple comparisons and there is a potential for directional errors when declaring genes to be up- or downregulated. Global gene expression patterns of tumors arising in response to the toxicant Vinylidene Chloride were compared to spontaneous mesotheliomas and F344/N rat mesothelial cells (Fred-PE) in order to discover the functions associated with VDC exposure. The data produced from VDC-treated animals suggested that exposure to this asbestos-related chemical is associated with the gene regulation of oncogenes, growth factors, and cell cycle response (Blackshear et al., 2014). A separate study addressed whether gene expression changes in human blood cells differ between individuals who are resistant or sensitive to sleep deprivation. We found that two genes (SREBF1 and CPT1A, associated with lipid metabolism) held small changes over time during sleep deprivation. We also found a reduction in amplitude of normally cycling transcripts due to sleep deprivation which was higher in resistant subjects compared to sensitive subjects (Arnardottir et al., 2014). Another study examined the dynamic expression of prion-like proteins in the pharynx of Caunorhabditis elegans. The grinder, a tooth-like specialization to crush food, lies at the posterior end of the pharynx. To study the structure of the grinder and pharynx cuticle, we examined the gene expression response during the molt. The results identified abu genes encoding prion-like proteins that were induced during the molt. Abnormal cuticle function resulted from knocking down genes in the abu/pqn paralog group. Transcriptinoal studies without precise staging might inappropriately find changes in these genes since they are strongly regulated during development (George-Raizen et al., 2014).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAES103166-03
Application #
9143516
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Perron, Isaac J; Keenan, Brendan T; Chellappa, Karthikeyani et al. (2018) Dietary challenges differentially affect activity and sleep/wake behavior in mus musculus: Isolating independent associations with diet/energy balance and body weight. PLoS One 13:e0196743
Dunnick, June K; Merrick, B Alex; Brix, Amy et al. (2016) Molecular Changes in the Nasal Cavity after N, N-dimethyl-p-toluidine Exposure. Toxicol Pathol 44:835-47
Hayes, Schantel A; Pandiri, Arun R; Ton, Thai-vu T et al. (2016) Renal Cell Carcinomas in Vinylidene Chloride-exposed Male B6C3F1 Mice Are Characterized by Oxidative Stress and TP53 Pathway Dysregulation. Toxicol Pathol 44:71-87
Blackshear, Pamela E; Pandiri, Arun R; Nagai, Hiroaki et al. (2015) Gene expression of mesothelioma in vinylidene chloride-exposed F344/N rats reveal immune dysfunction, tissue damage, and inflammation pathways. Toxicol Pathol 43:171-85
Bhusari, Sachin; Pandiri, Arun R; Nagai, Hiroaki et al. (2015) Genomic Profiling Reveals Unique Molecular Alterations in Hepatoblastomas and Adjacent Hepatocellular Carcinomas in B6C3F1 Mice. Toxicol Pathol 43:1114-26
George-Raizen, Julia B; Shockley, Keith R; Trojanowski, Nicholas F et al. (2014) Dynamically-expressed prion-like proteins form a cuticle in the pharynx of Caenorhabditis elegans. Biol Open 3:1139-49
Arnardottir, Erna S; Nikonova, Elena V; Shockley, Keith R et al. (2014) Blood-gene expression reveals reduced circadian rhythmicity in individuals resistant to sleep deprivation. Sleep 37:1589-600
Blackshear, Pamela E; Pandiri, Arun R; Ton, Thai-Vu T et al. (2014) Spontaneous mesotheliomas in F344/N rats are characterized by dysregulation of cellular growth and immune function pathways. Toxicol Pathol 42:863-76
Hoenerhoff, Mark J; Pandiri, Arun R; Snyder, Stephanie A et al. (2013) Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways. Toxicol Pathol 41:826-41
Anafi, Ron C; Pellegrino, Renata; Shockley, Keith R et al. (2013) Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues. BMC Genomics 14:362

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