We are exploiting the utility of C. elegans in studying conserved nutrient and stress signalling pathways. In collaboration with Iqbal Hamza's group (Univ of Maryland), we have continued to study how heme levels are sensed and regulated in animals using the C. elegans model system that provides unique advantages. During the past year, we completed a study of the heme-regulated gene number seven (HRG-7)that plays a role in inter-organ signalling and organismal heme homeostasis. In collaboration with John Hanover's group (NIDDK, NIH) and Dr. Miwa (retired), we completed a genetic study that identified novel players as well as know actors in the animals ability to detect and respond to toxins. The result of these studies was an expanded understanding of how endogenous and exogenous toxins are sensed and the trigger to activate the cascade of downstream events resulting in transcriptional activation of the genes necessary for the response.

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12
Fiscal Year
2018
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U.S. National Inst Diabetes/Digst/Kidney
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Fukushige, Tetsunari; Smith, Harold E; Miwa, Johji et al. (2017) A Genetic Analysis of the Caenorhabditis elegans Detoxification Response. Genetics 206:939-952
Sinclair, Jason; Pinter, Katherine; Samuel, Tamika et al. (2017) Inter-organ signalling by HRG-7 promotes systemic haem homeostasis. Nat Cell Biol 19:799-807
Chughtai, Ahmed Ali; Kaššák, Filip; Kostrouchová, Markéta et al. (2015) Perilipin-related protein regulates lipid metabolism in C. elegans. PeerJ 3:e1213
Ghosh, Salil K; Bond, Michelle R; Love, Dona C et al. (2014) Disruption of O-GlcNAc Cycling in C. elegans Perturbs Nucleotide Sugar Pools and Complex Glycans. Front Endocrinol (Lausanne) 5:197
Mikolas, Pavol; Kollarova, Johana; Sebkova, Katerina et al. (2013) GEI-8, a homologue of vertebrate nuclear receptor corepressor NCoR/SMRT, regulates gonad development and neuronal functions in Caenorhabditis elegans. PLoS One 8:e58462
Wang, Peng; Lazarus, Brooke D; Forsythe, Michele E et al. (2012) O-GlcNAc cycling mutants modulate proteotoxicity in Caenorhabditis elegans models of human neurodegenerative diseases. Proc Natl Acad Sci U S A 109:17669-74
Mondoux, Michelle A; Love, Dona C; Ghosh, Salil K et al. (2011) O-linked-N-acetylglucosamine cycling and insulin signaling are required for the glucose stress response in Caenorhabditis elegans. Genetics 188:369-82
Kouns, Nathaniel A; Nakielna, Johana; Behensky, Frantisek et al. (2011) NHR-23 dependent collagen and hedgehog-related genes required for molting. Biochem Biophys Res Commun 413:515-20
Severance, Scott; Rajagopal, Abbhirami; Rao, Anita U et al. (2010) Genome-wide analysis reveals novel genes essential for heme homeostasis in Caenorhabditis elegans. PLoS Genet 6:e1001044
Hanover, John A; Krause, Michael W; Love, Dona C (2010) The hexosamine signaling pathway: O-GlcNAc cycling in feast or famine. Biochim Biophys Acta 1800:80-95

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