Research in the Vulpe lab is currently focused on 3 areas of environmental toxicology 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 the laboratory is to further understand copper and iron metabolism in mammals.
Hephaestin (Hp) is a membrane-bound copper containing ferroxidase [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.
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.
We are utilizing systematic functional analysis through the use of “barcoding” analysis in the budding yeast Saccharomyces cerevisiae to identify genes involved in sensitivity and resistance to toxicants. We are currently focusing on metals, metalloids, and benzene and its metabolites, as well as pesticides and emerging contaminants, including flame retardants. Our long term goal is to identify conserved toxicity pathways which may influence susceptibility to toxicant exposure in eukaryotes including people.
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. Tools we are using include traditional microarray technologies as well as recently developed high-throughput sequencing methods.