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. Gene expression patterns from spontaneous tumors arising in untreated F344/N rats were compared with samples from untreated age-matched control animals. Upregulated genes were associated with growth factors, oncogenes, cytokines, and pathogen-associated molecular patterns receptors. In addition, the production of reactive oxygen and nitrogen species was affected (Blackshear et al., 2013). Apoptosis pathways were 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). In a different study, we evaluated the molecular profiles associated with sleep and sleep deprivation in heart and lung tissues. DNA microarrays were used to compare gene expression in tissue from sleeping and sleep deprived mice. A total of 3% and 6% of the measured transcripts were shown to be """"""""sleep specific"""""""" in the lung and heart, respectively. Processes associated with cellular stress and protein folding were reduced with sleep, while tissue-specific metabolic processes were enhanced with sleep (Anafi et al., 2013).

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
Zip Code
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

Showing the most recent 10 out of 12 publications