Chris Vulpe



Associate Professor
Associate Professor and Associate Toxicologist in the Agricultural Experiment Station
Ph.D. (Genetics), University of California, San Francisco, 1994
M.D., University of California, San Francisco, 1996

(510) 642-1834
 Chris Vulpe

My group is currently working in three areas of nutrition and toxicology

  1. Eukaryotic copper and iron metabolism including
    1. Hephaestin and Zyklopen, related mammalian ferroxidases, which are involved in cellular iron export
    2. Genetic modifiers of iron homeostasis in mice and humans
  2. Genomic approaches to identify conserved toxicity pathways in eukaryotes using S. cerevisiae with a focus on
    1. Metals and metalloids
    2. Benzene and metabolites
  3. Ecotoxicogenomics using the water flea, Daphnia magna and the Fathead minnow, Pimephales promelas as model organisms to develop new sensitive tools for
    1. Toxicant identification in freshwater ecosystems
    2. Screening for chemical toxicity
    3. Determining mode of action of environmental contaminants

Copper and iron metabolism


Copper and iron are vital nutrients with evolutionarily conserved and interwoven cellular and systemic metabolism, required for the growth and development of all organisms. An overall research goal of my laboratory is to further understand copper and iron metabolism in mammals.

Hephaestin


Hephaestin (Hp) is a membrane-bound copper containing ferrroxidase [converts Fe2+ to Fe 3+] involved in intestinal iron export. The heph gene is mutant in the sex linked anemia (sla) mouse. Our group has been involved in characterizing the function, activity and regulation of this protein and its important role in iron homeostasis in mammals.


Iron Transport through the Enterocyte

Zyklopen


Recently we identified another membrane bound ferroxidase, Zyklopen, which is expressed in distinct tissues from the characterized ferroxidases, Ceruloplasmin and Hephaestin. We are currently working to determine its role in mammalian iron metabolism.

Genetic modifiers of iron homeostasis


We are currently carrying out studies in both mice and people to identify genetic factors which influence iron status in mammals. In mice, we are performing an “in silico” QTL analysis of inbred strains of mice. In humans, we are collaborating on a large multi-center study to identify genetic determinants of iron deficiency.

Eukaryotic toxicity pathways


We are utilizing systematic functional analysis through the use of “barcoding” analysis in S.cerevisiae to identify genes involved in sensitivity and resistance to toxicants. We are currently focusing on metals, metalloids, and benzene and its metabolites. Our long term goal is identify conserved toxicity pathways which may influence susceptibility to toxicant exposure in eukaryotes including people.

Ecotoxicogenomics


We are developing a novel approach for identifying and understanding the toxicity of xenobiotics in aquatic ecosystems by monitoring changes in global gene expression patterns in aquatic indicator species representative of different trophic levels including Daphnia magna (a crustacean), and Pimephales promelas (fathead minnow). Our short-term goal is to assess the sensitivity and specificity of an ecotoxicogenomics approach to ecological toxicity assessment as compared to standard protocols while our long term goal is to assess its utility in real world environmental settings.

For more information, please visit the Vulpe Lab page.


Recent Publications

Eukaryotic copper and Iron Metabolism

Jo, W.J., et al., Novel insights into iron metabolism by integrating deletome and transcriptome analysis in an iron deficiency model of the yeast Saccharomyces cerevisiae. BMC Genomics, 2009. 10: p. 130.

Chen, H., et al., Age-related changes in iron homeostasis in mouse ferroxidase mutants. Biometals, 2009.

Chen, H., et al., Decreased hephaestin expression and activity leads to decreased iron efflux from differentiated Caco2 cells. J Cell Biochem, 2009.

Anderson, G.J. and C.D. Vulpe, Mammalian iron transport. Cell Mol Life Sci, 2009

Allen, K.J., et al., Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med, 2008. 358(3): p. 221-30.

Ecotoxicogenomics

Poynton, H. and C. Vulpe, Ecotoxicogenomics: Emerging Technologies for Emerging Contaminants. JAWRA Journal of the American Water Resources Association, 2009. 45(1): p. 83-96.

Garcia-Reyero, N., et al., The explosive side of Ecotoxicogenomics: Biomarker discovery and transcriptomic responses in Daphnia magna exposed to munitions constituents. Environmental Sciences and Technology, 2009. in press

Poynton, H.C., et al., Gene Expression Profiling in Daphnia magna, Part II: Validation of a Copper Specific Gene Expression Signature with Effluent from Two Copper Mines in California. Environ. Sci. Technol., 2008. 42(16): p. 6257-6263.

Poynton, H.C., H. Wintz, and C.D. Vulpe, Progress in ecotoxicogenomics for environmental monitoring, mode of action, and toxicant identification, in Advances in Experimental Biology, H. Christer and K. Peter, Editors. 2008, Elsevier. p. 21-73, 322-323.

Poynton, H.C., et al., Gene Expression Profiling in Daphnia magna Part I: Concentration-Dependent Profiles Provide Support for the No Observed Transcriptional Effect Level. Environ. Sci. Technol., 2008. 42(16): p. 6250-6256.

Toxicity Pathways

Lan, Q., et al., Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity. Carcinogenesis, 2009. 30(1): p. 50-8.

Jo, W.J., et al., Identification of Genes Involved in the Toxic Response of Saccharomyces cerevisiae against Iron and Copper Overload by Parallel Analysis of Deletion Mutants. Toxicol Sci, 2008. 101(1): p. 140-51.

Poynton, H.C., et al., Daphnia magna ecotoxicogenomics provides mechanistic insights into metal toxicity. Environmental science & technology, 2007. 41(3): p. 1044-50.

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