Detection and Models of Toxicant Exposure
The UCSD Superfund Research Center will be developing models through its Biomedical research projects to characterize the mechanisms of Superfund toxicant induced TASH development and cancer, while the Environmental Science & Engineering (ES&E) research projects will develop tools for NPL-toxicant detection and remediation. The Biomedical and ES&E projects will be assisted in these efforts by Research Core services that will provide tools for mouse genetic production, metabolomic and sophisticated Bioinformatic analysis. A key objective of the projects is to highlight scientific findings to maximize Research Translation, which will happen with collaborations between the projects and our Research Translation Core.
Nonalcoholic steatohepatitis (NASH) and toxicant-associated steatohepatitis (TASH) are common liver pathologies that cause hepatocyte damage, lead to hepatocellular carcinoma (HCC) development, and are inducible by diet, stress, or chronic exposure to toxic agents such as diethylnitrosamine (DEN) or carbon tetrachloride (CCl4). The objective of this project is to define the importance of specific B lymphocyte subpopulations in modulating the pathogenesis of toxicant- and obesity-induced liver fibrosis and cancer.
Project 2: Nuclear Receptor Mediated Epigenetic and Immune Cell Changes in Liver Fibrosis Resulting From Toxicant Exposure
Project 2 will define the molecular pathways by which toxicants promote liver damage, and develop potential therapies that can modulate wound healing and prevent liver fibrosis.
Triclosan (TCS) is an antimicrobial compound, present in over-the-counter health care products, and is an environmental toxicant that causes fatty liver disease or Toxicant Associated Steatohepatitis (TASH). Experiments are in progress to characterize the molecular and cellular events that lead to triclosan induced TASH.
Project 4: The Role of Reactive Oxygen Species and the Microbiome in Toxicant Induced Liver Fibrosis
Project 4 investigates the mechanism of the exacerbating effects of Superfund toxicants in promoting the obesity-associated liver fibrosis in animal models of NASH and in vitro model of "human liver in the dish". The project develops new detection systems and therapeutic strategies for Superfund toxicant-induced NASH-associated liver fibrosis.
Environmental Science and Engineering
The study of environmental chemical exposure requires sensitive reagents for toxicant detection. We create a new class of cheap, robust biosensors that will detect a range of toxicants/pollutants useful for on-site detection and research.
Project 6: Molecular Mechanisms of Heavy Metal Detoxification and Engineering Accumulation in Plants
Heavy metal Superfund toxicants cause liver disease, cancers and mental disorders. 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, the performance of plants needs to be increased for bioremediation. Furthermore, the accumulation of toxic heavy metals and arsenic from soils into edible tissues of crop plants is the primary pathway through which humans ingest toxic metals. We are characterizing key genes and pathways that function in heavy metal over-accumulation in plants for enhancing their bioremediation potential – and in crops for avoiding toxic heavy metal and arsenic accumulation in edible tissues.
UCSD Superfund Research Center
University of California, San Diego
9500 Gilman Drive, Mail Code 0722
La Jolla, CA 92093-0722