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.