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). We also know from recent clinical studies 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, our SRC 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 we 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 projects is to highlight scientific findings to maximize Research Translation, which will happen with collaborations between the projects and the Research Translation Core. We believe our 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, our 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, our 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.
Center Narrative Of key importance to the Superfund Research Program (SRP) and SRP?s primary stakeholders is the link between nutrition, health disparities and environmental toxicant exposure toward the development of fatty liver disease, steatohepatitis, cirrhosis and liver cancer. Work conducted at the UCSD SRP Center is dedicated towards understanding the mechanisms associated with toxicant-induced steatohepatitis (TASH) and cancer, which may be an escalating problem in many susceptible Hispanic and American Indian communities that are exposed to household, occupational and industrial chemical exposure. Our efforts will provide important findings linking mechanisms of TASH and cancer with disease prognosis, which can be communicated to impacted communities to serve as intervention tools to assist in prevention of toxicant exposure.
|Tripathi, Anupriya; Debelius, Justine; Brenner, David A et al. (2018) Publisher Correction: The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 15:785|
|Zhang, Yuqin; Nasser, Victoria; Pisanty, Odelia et al. (2018) A transportome-scale amiRNA-based screen identifies redundant roles of Arabidopsis ABCB6 and ABCB20 in auxin transport. Nat Commun 9:4204|
|Tõldsepp, Kadri; Zhang, Jingbo; Takahashi, Yohei et al. (2018) Mitogen-activated protein kinases MPK4 and MPK12 are key components mediating CO2 -induced stomatal movements. Plant J 96:1018-1035|
|Li, Zixing; Takahashi, Yohei; Scavo, Alexander et al. (2018) Abscisic acid-induced degradation of Arabidopsis guanine nucleotide exchange factor requires calcium-dependent protein kinases. Proc Natl Acad Sci U S A 115:E4522-E4531|
|Hoffmann, Hanne M; Gong, Ping; Tamrazian, Anika et al. (2018) Transcriptional interaction between cFOS and the homeodomain-binding transcription factor VAX1 on the GnRH promoter controls Gnrh1 expression levels in a GnRH neuron maturation specific manner. Mol Cell Endocrinol 461:143-154|
|Zhong, Zhenyu; Liang, Shuang; Sanchez-Lopez, Elsa et al. (2018) New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 560:198-203|
|Wei, Zong; Yoshihara, Eiji; He, Nanhai et al. (2018) Vitamin D Switches BAF Complexes to Protect ? Cells. Cell 173:1135-1149.e15|
|Caussy, Cyrielle; Hsu, Cynthia; Lo, Min-Tzu et al. (2018) Link between gut-microbiome derived metabolite and shared gene-effects with hepatic steatosis and fibrosis in NAFLD. Hepatology :|
|McNulty, Reginald; Cardone, Giovanni; Gilcrease, Eddie B et al. (2018) Cryo-EM Elucidation of the Structure of Bacteriophage P22 Virions after Genome Release. Biophys J 114:1295-1301|
|Song, Na-Young; Zhu, Feng; Wang, Zining et al. (2018) IKK? inactivation promotes Kras-initiated lung adenocarcinoma development through disrupting major redox regulatory pathways. Proc Natl Acad Sci U S A 115:E812-E821|
Showing the most recent 10 out of 404 publications