Soils and waters with high levels of toxic heavy metal(loid)s such as arsenic, cadmium and mercury are detrimental to human and environmental health. These three metal(loid)s are among the Superfund's top 7 priority hazardous substances. Research and applications indicate that uptake of heavy metals into plants via the root system and accumulation of heavy metals in plant shoots could provide a cost effective approach for toxic metal removal and remediation of heavy metal-laden soils and waters. However important genes and pathways that function in heavy metal over-accumulation in plants remain to be identified. In recent research we have made major advances at understanding key mechanisms that function in heavy metal detoxification, transport and accumulation in plants. We will combine powerful genomic, genetic, biochemical and physiological approaches to test new central hypotheses by pursuing the following Specific Aims: L Characterize newly identified vacuolar membrane transporters that function in uptake and accumulation of phytochelatin-heavy metal(loid) complexes into plant vacuoles and analyze their bioremediation potential. l Understanding the control of heavy metal accumulation and distribution in roots and shoots is critical for engineering of plants for bioremediation. Determine the mechanisms by which a new peptide transporter mutant, opt3, causes hyper-accumulation in roots and under-accumulation of cadmium in plant leaves. iii Our recent research has shown that heavy metal-chelating and detoxifying thiols undergo long distance transport in plants. However, the plasma membrane transporters for uptake of glutathione (GSH) and phytochelatins (PCs) remain unknown. Using a high-throughput screen we have now identified OPT4 as a putative GSH &PC-Cd transporter. We will characterize 0PT4 and additional transporters to determine their underlying GSH/PC-Cd/As transport mechanisms and their functions in heavy metal distribution in plants. IV. The mechanisms and transcription factors that mediate rapid heavy metal-induced gene expression in plants remain largely unknown, but are important for heavy metal resistance and accumulation. The genes of newly isolated mutants impaired in cadmium-induced gene expression will be identified and their functions characterized. Furthermore, a potent genome-wide approach has been developed and will be pursued to identify and characterize key transcription factors and repressors that control cadmium- and arsenic-induced gene expression. We will work closely with the RTC and CEC in sharing our advances and foremost in translational analyses of our findings for their potential in phytoremediafion of contaminated soils and waters.

Public Health Relevance

Soils and waters with high levels of toxic heavy metal(loid)s such as arsenic (As), cadmium (Cd) and mercury (Hg) are detrimental to human health. These heavy metal(loid)s are among the top 7 priority hazardous substances at US Superfund sites and uptake of toxic heavy metal(loid)s into plants has been proposed to provide a cost effective approach for toxic metal removal and bioremediation of heavy metalladen soils and waters. Important genes and pathways that function in heavy metal bioremediation and rapid As- and Cd-induced gene expression will be characterized and identified and their bioremediation potential analyzed, which could contribute to cost effective future clean up technologies.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1-JAB-J (SF))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
La Jolla
United States
Zip Code
Wall, Christopher E; Yu, Ruth T; Atkins, Anne R et al. (2016) Nuclear receptors and AMPK: can exercise mimetics cure diabetes? J Mol Endocrinol 57:R49-58
Liu, Weilin; Struik, Dicky; Nies, Vera J M et al. (2016) Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A 113:2288-93
Hirashima, Rika; Michimae, Hirofumi; Takemoto, Hiroaki et al. (2016) Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity. Mol Pharmacol 90:265-74
Park, Charlie C; Nguyen, Phirum; Hernandez, Carolyn et al. (2016) Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients with Biopsy-proven Nonalcoholic Fatty Liver Disease. Gastroenterology :
Guo, Lan; Ganguly, Abantika; Sun, Lingling et al. (2016) Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast. G3 (Bethesda) 6:3317-3333
Karin, Michael; Dhar, Debanjan (2016) Liver carcinogenesis: from naughty chemicals to soothing fat and the surprising role of NRF2. Carcinogenesis 37:541-6
Booth, D R; Ding, N; Parnell, G P et al. (2016) Cistromic and genetic evidence that the vitamin D receptor mediates susceptibility to latitude-dependent autoimmune diseases. Genes Immun 17:213-9
Umemura, Atsushi; He, Feng; Taniguchi, Koji et al. (2016) p62, Upregulated during Preneoplasia, Induces Hepatocellular Carcinogenesis by Maintaining Survival of Stressed HCC-Initiating Cells. Cancer Cell 29:935-48
Liu, Miao; Chen, Shujuan; Yueh, Mei-Fei et al. (2016) Cadmium and arsenic override NF-κB developmental regulation of the intestinal UGT1A1 gene and control of hyperbilirubinemia. Biochem Pharmacol 110-111:37-46
Hsin, I-Fang; Montano, Erica; Seki, Ekihiro (2016) Finding a new role for NEMO: A key player in preventing hepatocyte apoptosis and liver tumorigenesis by inhibiting RIPK1. Hepatology 64:295-7

Showing the most recent 10 out of 331 publications