Christopher D. Vulpe
- M.D., Medicine, University of California, San Francisco, 1996
- Ph.D., Biochemistry, Genetics, University of California, San Francisco, 1994
- S.B., Biology, Massachusetts Institute of Technology, 1986
We are developing novel approaches for identifying and understanding the toxicity of chemicals and nanomaterials in aquatic ecosystems. We are focused on the aquatic indicator species Daphnia magna (a crustacean) as well as representative fish species such as Rainbow Trout. We haveMost recently, we are focused on developing a mechanistic understanding the effects of silver nanowires in these species. We are also developing CRISPR based approaches to assess the function of toxicant related genes.
Genetics of Iron Homeostasis
Genetic variants influence iron homeostasis in mammals. My group has utilized genome wide approaches to identify genetic factors that influence iron status in mammals. Recently, we performed an association analysis of over 100 inbred strains of mice to identify genetic determinants of iron status in collaboration with Jake Lusis and Eleazar Eskin at UCLA. Ongoing work is to determine the functional role of candidate genes identified in these studies.
Mammalian ferroxidases – Hephaestin
Intestinal iron absorption is remarkably balanced to provide adequate iron to meet the body’s iron needs while preventing toxic excess. In a collaboration with Greg Anderson from QIMR, Brisbane Australia, Hephaestin (Hp) was identified to be a membrane-bound copper containing ferrroxidase required for export of iron from the intestinal enterocyte into the circulation. We have utilized floxed Hephaestin (Heph) to generate both complete and tissue specific knockouts confirming that global and intestinal specific knockouts result in systemic iron deficiency. Furthermore, we have developed mice which lack both Hephaestin and Ceruloplasmin, the circulating ferroxidase, which develop a much more severe phenotype of iron deficiency than either alone and provide compelling evidence for complementary and partially compensatory functions. In collaboration with Huijun Chen, at Nanjing University, we have demonstrated increased iron levels in many regions of the brain in mice lacking the Heph gene. Most recently, we have been analyzing the molecular mechanisms of the hairloss phenotype associated with iron deficiency in Heph KO mice.
- Poynton HC, Hasenbein S, Benoit JB, Sepulveda MS, Poelchau MF, Hughes DST, Murali SC, Chen S, Glastad KM, Goodisman MAD, Werren JH, Vineis JH, Bowen JL, Friedrich M, Jones J, Robertson HM, Feyereisen R, Mechler-Hickson A, Mathers N, Lee CE, Colbourne JK, Biales A, Johnston JS, Wellborn GA, Rosendale AJ, Cridge AG, Munoz-Torres MC, Bain PA, Manny AR, Major KM, Lambert FN, Vulpe CD, Tuck P, Blalock BJ, Lin YY, Smith ME, Ochoa-Acuna H, Chen MM, Childers CP, Qu J, Dugan S, Lee SL, Chao H, Dinh H, Han Y, Doddapaneni H, Worley KC, Muzny DM, Gibbs RA, Richards S. The Toxicogenome of Hyalella azteca: A Model for Sediment Ecotoxicology and Evolutionary Toxicology. Environ Sci Technol. 2018;52(10):6009-22. doi: 10.1021/acs.est.8b00837. PubMed PMID: 29634279.
- Luo H, Wang F, Zha J, Li H, Yan B, Du Q, Yang F, Sobh A, Vulpe C, Drusbosky L, Cogle C, Chepelev I, Xu B, Nimer SD, Licht J, Qiu Y, Chen B, Xu M, Huang S. CTCF boundary remodels chromatin domain and drives aberrant HOX gene transcription in acute myeloid leukemia. Blood. 2018. doi: 10.1182/blood-2017-11-814319. PubMed PMID: 29760161.
- Zheng J, Jiang R, Chen M, Maimaitiming Z, Wang J, Anderson GJ, Vulpe CD, Dunaief JL, Chen H. Multi-Copper Ferroxidase-Deficient Mice Have Increased Brain Iron Concentrations and Learning and Memory Deficits. J Nutr. 2018;148(4):643-9. doi: 10.1093/jn/nxy012. PubMed PMID: 29659961.
- Koppe T, Patchen B, Cheng A, Bhasin M, Vulpe C, Schwartz RE, Moreno-Navarrete JM, Fernandez-Real JM, Pissios P, Fraenkel PG. Nicotinamide N-methyltransferase expression decreases in iron overload, exacerbating toxicity in mouse hepatocytes. Hepatol Commun. 2017;1(8):803-15. doi: 10.1002/hep4.1083. PubMed PMID: 29404495; PubMed Central PMCID: PMCPMC5678920.
- De La Rosa VY, Asfaha J, Fasullo M, Loguinov A, Li P, Moore LE, Rothman N, Nakamura J, Swenberg JA, Scelo G, Zhang L, Smith MT, Vulpe CD. Editor’s Highlight: High-Throughput Functional Genomics Identifies Modulators of TCE Metabolite Genotoxicity and Candidate Susceptibility Genes. Toxicol Sci. 2017;160(1):111-20. doi: 10.1093/toxsci/kfx159. PubMed PMID: 28973557.
- McLachlan S, Page KE, Lee SM, Loguinov A, Valore E, Hui ST, Jung G, Zhou J, Lusis AJ, Fuqua B, Ganz T, Nemeth E, Vulpe CD. Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice. Am J Physiol Gastrointest Liver Physiol. 2017;313(5):G511-G23. doi: 10.1152/ajpgi.00307.2016. PubMed PMID: 28798083; PubMed Central PMCID: PMCPMC5792216.
- Feswick A, Isaacs M, Biales A, Flick RW, Bencic DC, Wang RL, Vulpe C, Brown-Augustine M, Loguinov A, Falciani F, Antczak P, Herbert J, Brown L, Denslow ND, Kroll KJ, Lavelle C, Dang V, Escalon L, Garcia-Reyero N, Martyniuk CJ, Munkittrick KR. How consistent are we? Interlaboratory comparison study in fathead minnows using the model estrogen 17alpha-ethinylestradiol to develop recommendations for environmental transcriptomics. Environ Toxicol Chem. 2017. doi: 10.1002/etc.3799. PubMed PMID: 28316117.
- De La Rosa VY, Asfaha J, Fasullo M, Loguinov A, Li P, Moore LE, Rothman N, Nakamura J, Swenberg J, Scelo G, Zhang L, Smith MT, Vulpe CD. High throughput functional genomics identifies modulators of TCE metabolite genotoxicity and candidate susceptibility genes. Toxicol Sci. 2017. doi: 10.1093/toxsci/kfx159. PubMed PMID: 28973557.
- Buckley HL, Hart-Cooper WM, Kim JH, Faulkner DM, Cheng LW, Chan KL, Vulpe CD, Orts WJ, Amrose SE, Mulvihill MJ. Design and Testing of Safer, More Effective Preservatives for Consumer Products. ACS Sustainable Chemistry & Engineering. 2017;5(5):4320-31. doi: 10.1021/acssuschemeng.7b00374.
- Doguer C, Ha J-H, Gulec S, Vulpe CD, Anderson GJ, Collins JF. Intestinal hephaestin potentiates iron absorption in weanling, adult, and pregnant mice under physiological conditions. Blood Advances. 2017;1(17):1335-46. doi: 10.1182/bloodadvances.2017008359.
- Faulkner D, Rubin Shen LK, De La Rosa VY, Johnson DE, Hemingway R, Williams RV, Judson PN, Arnold J, Vulpe CD. CHAPTER 3 Tools for Green Molecular Design to Reduce Toxicological Risk. Computational Systems Pharmacology and Toxicology: The Royal Society of Chemistry; 2017. p. 36-59.
Last updated 30 Nov 2018