Ziwei received her BE in biopharmaceutics at Beijing University of Chinese Medicine. She obtained her PhD in Nutritional Biology at UC Davis, where she worked in the laboratory of Dr. Patricia Oteiza investigating the mechanisms involved in the beneficial effects of (-)-epicatechin on high-fat-induced intestinal permeability and endotoxemia. She currently works as a postdoctoral fellow, establishing a platform to rapidly validate the functional impact of genetic alterations in tumor cells and potential therapeutic targets in the stromal cells of primary tumors. She is as passionate about working in the lab as she is about enjoying nature by doing outdoor activities like hiking, skiing, travelling, and trying out new foods.
Doctor of Philosophy, University of California Davis (2021)
Bachelor of Engineering, Unlisted School (2014)
Ph.D., University of California, Davis, Nutritional Biology (2021)
B.E., Beijing University of Chinese Medicine, Biopharmaceutics (2014)
Everett Moding, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
My current work focuses on establishing preclinical platforms to rapidly validate the functional impact of genetic alterations in tumors using both cell and genetically engineered mouse models. We hope this system can accelerate the discovery and translation of novel cancer therapies to patients.
(-)-Epicatechin and NADPH oxidase inhibitors prevent bile acid-induced Caco-2 monolayer permeabilization through ERK1/2 modulation.
2020; 28: 101360
Secondary bile acids promote gastrointestinal (GI) tract permeabilization both in vivo and in vitro. Consumption of high fat diets increases bile acid levels in the GI tract which can contribute to intestinal permeabilization and consequent local and systemic inflammation. This work investigated the mechanisms involved in bile acid (deoxycholic acid (DCA))-induced intestinal epithelial cell monolayer permeabilization and the preventive capacity of (-)-epicatechin (EC). While EC prevented high fat diet-induced intestinal permeabilization in mice, it did not mitigate the associated increase in fecal/cecal total and individual bile acids. In vitro, using differentiated Caco-2 cells as a model of epithelial barrier, EC and other NADPH oxidase inhibitors (VAS-2870 and apocynin) mitigated DCA-induced Caco-2 monolayer permeabilization. While EC inhibited DCA-mediated increase in cell oxidants, it did not prevent DCA-induced mitochondrial oxidant production. Prevention of DCA-induced ERK1/2 activation with EC, VAS-2870, apocynin and the MEK inhibitor U0126, also prevented monolayer permeabilization, stressing the key involvement of ERK1/2 in this process and its redox regulation. Downstream, DCA promoted myosin light chain (MLC) phosphorylation which was related to MLC phosphatase (MLCP) inhibition by ERK1/2. DCA also decreased the levels of the tight junction proteins ZO-1 and occludin, which can be related to MMP-2 activation and consequent ZO-1 and occludin degradation. Both events were prevented by EC, NADPH oxidase and ERK1/2 inhibitors. Thus, DCA-induced Caco-2 monolayer permeabilization occurs mainly secondary to a redox-regulated ERK1/2 activation and downstream disruption of TJ structure and dynamic. EC's capacity to mitigate in vivo the gastrointestinal permeabilization caused by consumption of high-fat diets can be in part related to its capacity to inhibit bile-induced NADPH oxidase and ERK1/2 activation.
View details for DOI 10.1016/j.redox.2019.101360
View details for PubMedID 31677553
View details for PubMedCentralID PMC6920094
(-)-Epicatechin and the comorbidities of obesity.
Archives of biochemistry and biophysics
2020; 690: 108505
Obesity has major adverse consequences on human health contributing to the development of, among others, insulin resistance and type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease, altered behavior and cognition, and cancer. Changes in dietary habits and lifestyle could contribute to mitigate the development and/or progression of these pathologies. This review will discuss current evidence on the beneficial actions of the flavan-3-ol (-)-epicatechin (EC) on obesity-associated comorbidities. These benefits can be in part explained through EC's capacity to mitigate several common events underlying the development of these pathologies, including: i) high circulating levels of glucose, lipids and endotoxins; ii) chronic systemic inflammation; iii) tissue endoplasmic reticulum and oxidative stress; iv) insulin resistance; v) mitochondria dysfunction and vi) dysbiosis. The currently known underlying mechanisms and cellular targets of EC's beneficial effects are discussed. While, there is limited evidence from human studies supplementing with pure EC, other studies involving cocoa supplementation in humans, pure EC in rodents and in vitro studies, support a potential beneficial action of EC on obesity-associated comorbidities. This evidence also stresses the need of further research in the field, which would contribute to the development of human dietary strategies to mitigate the adverse consequences of obesity.
View details for DOI 10.1016/j.abb.2020.108505
View details for PubMedID 32679195
(-)-Epicatechin mitigates high fat diet-induced neuroinflammation and altered behavior in mice.
Food & function
2020; 11 (6): 5065-5076
Obesity is characterized by a condition of low-level chronic inflammation that can lead to altered cognition and behavior. The flavanol (-)-epicatechin (EC) has been shown to have anti-inflammatory actions in mouse models of diet-induced obesity. This study investigated the capacity of dietary EC to mitigate hippocampal inflammation and impaired memory in high fat diet (HFD)-fed mice. Healthy 6 weeks old male C57BL/6J mice (10 mice per group) were fed for 13 weeks either: a control diet (10% total calories from fat), a high fat diet (60% total calories from fat), or the control and high fat diets supplemented with 20 mg EC per kg body weight. Short-term object recognition memory was evaluated by the novel object recognition (NOR) task and spatial memory by the object location memory (OLM) task and the Morris water maze (MWM). After 13 weeks on the dietary treatments, HFD-fed mice developed obesity, which was not affected by EC supplementation. HFD consumption caused metabolic endotoxemia, and increases in parameters of hippocampal inflammation, i.e. mRNA levels of TLR4, Iba-1, and NOX4. All these changes were mitigated by EC supplementation. EC supplementation also significantly improved recognition memory in HFD-fed mice while neither HFD consumption nor EC supplementation affected mouse spatial memory. Overall, EC supplementation prevented short-term recognition memory impairment in HFD-induced obese mice, which could be in part due to the capacity of EC to mitigate metabolic endotoxemia and associated hippocampal inflammation and oxidative stress.
View details for DOI 10.1039/d0fo00486c
View details for PubMedID 32432285
(-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance.
2018; 14: 588-599
Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD) is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (-)-epicatechin (EC) supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance. Mechanisms leading to loss of integrity and function of the tight junction (TJ) were characterized. Consumption of a HFD for 15 weeks caused obesity, steatosis, and insulin resistance in male C57BL/6J mice. This was associated with increased intestinal permeability, decreased expression of ileal TJ proteins, and endotoxemia. Supplementation with EC (2-20mg/kg body weight) mitigated all these adverse effects. EC acted modulating cell signals and the gut hormone GLP-2, which are central to the regulation of intestinal permeability. Thus, EC prevented HFD-induced ileum NOX1/NOX4 upregulation, protein oxidation, and the activation of the redox-sensitive NF-κB and ERK1/2 pathways. Supporting NADPH oxidase as a target of EC actions, in Caco-2 cells EC and apocynin inhibited tumor necrosis alpha (TNFα)-induced NOX1/NOX4 overexpression, protein oxidation and monolayer permeabilization. Together, our findings demonstrate protective effects of EC against HFD-induced increased intestinal permeability and endotoxemia. This can in part underlie EC capacity to prevent steatosis and insulin resistance occurring as a consequence of HFD consumption.
View details for DOI 10.1016/j.redox.2017.11.002
View details for PubMedID 29154190
View details for PubMedCentralID PMC5691220