Julia Yue Cui, PhD

Mentorship

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DEOHS Students Mentored

Research

Interests: Developmental exposure to environmental chemicals. Epigenetic memory and nuclear receptor-signaling to modulate drug metabolism and transport during and beyond childhood. Gut microbiome, drug metabolism and obesity. Developmental reprogramming of gut microbiome by probiotics and antibiotics and modulating pediatric pharmacology and childhood obesity.

Projects

Developmental regulation of drug-processing genes. Despite recent rapid progress in understanding the expression patterns and regulatory mechanisms of drug-processing genes, namely drug-metabolizing enzymes and transporters in adults, little is known about these in the pediatric period. The long-term goal is to understand mechanisms of ontogenic regulation of drug-processing genes so that efficacious and safe drug treatments can be achieved in children. This study is novel because it uses a genome-wide approach to elucidate how alterations of hormones and transcription factors modulate epigenetic signatures and hepatic ontogenic expression of drug-processing genes. Results will provide basic knowledge on the ontogenic expression patterns of drug-processing genes and nuclear receptors in liver, kidney and intestine and help to understand how perinatal alterations in hormones and nuclear receptors, via modulating epigenetic signatures, affect stage-specific and long-term expression of drug-processing genes.

Developmental regulation of drug metabolism by targeting the gut microbiome. Very little is known about the developmental regulation of drug-metabolizing enzymes and transporters (together called "drug-processing genes" [DPGs]) in the liver, placing newborns and children at a much higher risk of adverse drug reactions. Using RNA-Seq, we have shown that drug metabolism is the top most differentially regulated pathway in the entire liver transcriptome of germ-free mice, suggesting that there is a novel interaction between gut microbiome and hepatic DPGs. The goal of this research is to utilize multidisciplinary approaches, including germ-free and genetically engineered mice, BA metabolomics, Next-Generation Sequencing and human fecal samples, to unveil the role of gut microbiota in modulating signaling from the two most critical xenobiotic-sensing nuclear receptors in the liver, namely the pregnane X receptor and constitutive androstane receptor, and the subsequent ontogenic re-programming of DPGs in the liver. The research will lead to a paradigm shift in pediatric pharmacology by establishing a new concept in considering adverse drug reactions in children.

Epigenetic regulation of drug metabolism by developmental exposure to PBDEs. Developmental exposure to the flame-retardant polybrominated diphenyl ethers (PBDEs) has attracted growing concerns because these highly persistent environmental toxicants are accumulated much more in infants through breast milk and produce multiple detrimental effects. Little is known about the potential involvement of PBDEs in modulating the pharmacokinetics of drugs in newborns and children. The objective of this research is to utilize multidisciplinary approaches to strategically investigate the epigenetic mechanisms of PBDEs in modulating the transcriptional activities of the major xenobiotic-sensing nuclear receptors pregnane X receptor (PXR) and constitutive and rostane receptor (CAR) and drug-processing capacities during and beyond the neonatal period on a genome-wide scale.

Publications

Selected publications

• The disposition of polychlorinated biphenyls (PCBs) differs between germ-free and conventional mice
• PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice
• Understanding the physiological functions of the host xenobiotic-sensing nuclear receptors PXR and CAR on the gut microbiome using genetically modified mice
• Physiological Regulation of Drug Metabolism and Transport: Pregnancy, Microbiome, Inflammation, Infection, and Fasting
• Gut microbiome: An intermediary to neurotoxicity

Engagement

Equity, diversity and inclusion

The microbiome is an important regulator for exposures to environmental toxicants that can lead to adverse health effects such as liver cancer, obesity and neurodegenerative disease, especially in vulnerable populations that are either genetically predisposed or are at increased risk of exposures to environmental stressors. My work contributes to public health practice by investigating the mechanisms of how the microbiome contributes to these adverse health effects and identifying novel biomarkers. Results will provide insights into informing risks and designing precision microbial therapies to mitigate the injury in susceptible populations.

Community and research partnerships

I have ongoing collaborations with investigators from the Fred Hutchinson Cancer Research Center and the Institute for Systems Biology on translational research regarding how the microbiome contributes to the susceptibility of diseases in confined environments and in vulnerable populations.  

Other collaborators include: 

• The CMiST Microbiome Center
• The Seattle VA Medical Center
• Florida International University
• The Albert Einstein College of Medicine
• University of Iowa Superfund Research Program
• University of California, Davis
• Institute for Systems Biology
• UW Tacoma Environmental Chemistry and Engineering  

Teaching practices

I use state-of-the-art active learning classroom (ALC) teaching strategies to promote engagement with students from diverse backgrounds. I provide opportunities for student-led guest lectures and group discussions and empower students to develop their own research topics for case studies. I welcome the many social and cultural differences among us, and I engage respectfully in the discussion of diverse world views and ideologies embedded in course readings, presentations and artifacts, including those course materials that are at odds with personal beliefs and values.  

Besides classroom teaching, I provide independent research study opportunities to students from diverse backgrounds, including trainees from the SURE-EH program (https://deohs.washington.edu/sure-eh), which provides underrepresented students at the UW with an opportunity to work with experienced faculty on a research project addressing the relationship between environmental exposures and human health. 

Success stories from my trainees include winning the UW Mary Gates Scholarship, winning best research presentation awards at scientific meetings, and co-authoring publications in peer-reviewed journals in the area of environmental health sciences.  

Service

• DEOHS Roosevelt Advisory Committee  
• DEOHS CAPC Course Curriculum Committee  
• DEOHS Graduate Student Admission Committee
• NIEHS R21 SURE-EH training grant, Steering Committee
• NIEHS T32 EP/T training grant, Steering Committee
• CMiST Microbiome Center Steering Committee
• EHMBRACE Microbiome Center Director and Steering Committee
• Various thesis committees in DEOHS, Engineering, Pharmaceutical Sciences, Medicinal Chemistry and Biostatistics
• NIH Standing Member of the SIEE Study Section
• American Society for Pharmacology and Experimental Therapeutics (ASPET) Executive Committee
• Society of Toxicology (SOT) Award Committee
• Pacific Northwest Association for Toxicologists (PANWAT) President and Executive Committee  
• 2021: Co-chair and organizer of the UW-ASU (Arizona State University) Metabolomics and Microbiomics Symposium
• NIH Study section reviewer on the ZRG1 DKUS-A (04) specialty section
• Co-director of the Functional Genomics Core of the NIEHS EDGE Center
• Member of the Seattle Cancer Consortium 

Media Mentions