University of California-San Diego
Superfund Research Program
Detection and Models of Toxicant Exposure
Center Director: Robert H. Tukey
Grant Number: P42ES010337
Funding Period: 2000-2022
Nonalcoholic fatty liver disease (NAFLD) is escalating in California and the United States and is associated with the rising obesity epidemic. NAFLD is a hepatic phenotype that encompasses the more serious manifestation of steatohepatitis (NASH), considered to be a prerequisite for liver cancer (hepatocellular carcinoma/HCC). Recent clinical studies show that chemical toxicant exposure, in the absence of obesity, can lead to toxicant-associated steatohepatitis (TASH), which closely resembles the pathology of NASH. These findings are relevant to SRP stakeholders in Region 9, since California ranks high in National Priorities List (Superfund sites) nationally and contains thousands of additional hazardous waste sites (HWS). In addition, the UCSD NAFLD Research Center shows that American Indians and Hispanics, combined the largest non-Caucasian population in California, are at far greater risk of developing NAFLD. Over the past five years, the UCSD SRP Center has leveraged resources to demonstrate that TASH is greatly accelerated by consumption of high-fat diet (HFD) or after a diabetic episode in mice. These findings are relevant, since the researchers can speculate that American Indians and Hispanics are more susceptible to TASH development, a risk amplified by unhealthy diets, poverty and health disparities. The UCSD SRC will be developing models through its Biomedical projects to characterize the mechanisms of Superfund toxicant induced TASH development and cancer, while the Environmental Science & Engineering (ES&E) projects will develop tools for NPL-toxicant detection and remediation. 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 Center is to highlight scientific findings to maximize research translation, which will happen with collaborations between the projects and the Research Translation Core. UCSD researchers believe their program is innovative and paradigm shifting, since it has the potential of linking important basic research findings regarding Superfund toxicant exposure with human disease biomarker identification through collaborations with the UCSD NAFLD Research Center, which contains one of the largest NALFD cohort studies in the world. Importantly, their Biomedical findings and tools developed in the ES&E projects will be used as resources and knowledge gained to reduce cumulative impacts and health disparities. These initiatives will be leveraged through Community Engagement Core efforts in disadvantaged Hispanic neighborhoods in San Diego and Mexico where statistics confirms that obesity is an escalating problem both in children and adults. Since the incidence of NAFLD and liver cirrhosis is on the rise in both children and adults and may be linked to toxicant chemical exposure, findings will be communicated to SRP primary stakeholders at the U.S. Environmental Protection Agency and the Agency for Toxic Substances and Disease Registry, in addition to state and local agencies.