One of our current projects is to use zebrafish as a new animal model to investigate arsenic-associated pathologies. We developed zebrafish model in the study of arsenic toxicology. The first stage of our study is investigating major arsenic metabolic functions in zebrafish—arsenic transport and methylation—and to compare to those in humans. Our past work showed zebrafish share very similar mechanisms in arsenic transport and methylation which validate this model for future studies, including the exploration of important arsenic molecular targets, determining the effect of genetic modification of major arsenic related enzymes, studying pathologies under chronic arsenic exposure, and applying large scale screening of arsenic-remediation drugs. These studies will eventually contribute to the elucidation of the arsenic associated human diseases and the search for possible prevention and treatment approaches.
Research Project 1:
Research Project 2:
Our second project is to identify and characterize the currently unknown transporter for selenium. Selenium is both a required micronutrient and treatment reagent in multiple human diseases. As selenite has an extremely narrow concentration which determines its functional effects it has been hypothesized that the membrane transporter plays a major role in regulating selenite dose response. Selenite is a potent form of selenium with unique clinically important effects and a growing amount of promising applications in many clinical and preclinical trials. Although selenite is known to have potent anti-cancer and anti-inflammatory properties, the lack of knowledge in how membrane transporters regulate selenite uptake prevents our ability to take advantage of its benefits and to prevent toxic side-effects. Therefore the identification of the selenite transporter and detailed knowledge of its mechanisms is a missing link in both basic selenium research and in its broad clinical applications. In 2010 our lab identified the major selenite transporter in S. cerevisiae and has since attempted to identify selenite transporters in mammals. Progress in the past two years led to defining the strict conditions required for selenite uptake and allowed us to screen membrane proteins for selenite uptake. We successfully identified the first human selenite transporter which we believe to be a breakthrough in selenium research. Currently we are expanding the characterization of this protein further define the physiological significance of this new transport mechanism. In the future we will continue to explore the relationship of selenite transporter with selenite pharmacokinetics and the influence of this on selenite therapeutic application.