Ekuban Laboratory of Environmental Hepatology And Toxicology (ELEHAT)

About

The Ekuban Laboratory of Environmental Hepatology And Toxicology (ELEHAT), investigates how environmental exposures influence liver health, particularly in the context of alcohol use and metabolic stress. The laboratory focuses on environmental pollutants, especially per- and polyfluoroalkyl substances (PFAS), as potential disease-modifying factors in alcohol-associated liver disease and related metabolic liver disorders.

Our research integrates toxicology, hepatology, molecular biology, animal models, cell culture systems, histology, and translational approaches to understand why only a subset of individuals exposed to alcohol or metabolic stress develop severe liver injury. A central goal of ELEHAT is to define how environmental chemicals disrupt biological pathways in the liver and connected extrahepatic organs, including the gut, adipose tissue, and brain. Through this work, ELEHAT aims to identify modifiable environmental risk factors and support future prevention and intervention strategies for liver disease.

Key Research Areas

Environmental pollutants as disease-modifying factors in liver disease
PFAS exposure and liver injury
Alcohol-associated liver disease
PFAS-alcohol interactions
Gut-liver axis in toxicant-associated liver injury
Adipose-liver axis and metabolic dysfunction
Nuclear receptor signaling and xenobiotic metabolism
Human primary hepatocyte models for translational toxicology
Inflammation, oxidative stress, lipid dysregulation, and organ crosstalk
Translational environmental hepatology and prevention strategies
ELEHAT PFAS-Alcohol Research Program
The ELEHAT research program investigates how PFAS interact with alcohol exposure to influence liver disease risk, progression, and severity. The central premise is that environmental exposures may help explain why only a subset of individuals with alcohol exposure develop severe alcohol-associated liver disease. The program follows a translational framework that begins with human exposure assessment and moves into experimental models designed to test causality, mechanisms, human relevance, structural diversity, and intervention strategies.

Research Pillar	Focus	Description for Webpage
Human Exposome	PFAS exposure assessment in human alcohol-associated hepatitis	ELEHAT analyzes PFAS concentrations in de-identified plasma samples from patients with alcohol-associated hepatitis across varying levels of disease severity to determine whether PFAS exposure profiles are associated with clinical outcomes and disease progression.
Reverse Translation	Mouse models informed by human exposure questions	Human exposure findings are reverse translated into experimental mouse models to determine whether PFAS exposures can modify alcohol-induced liver injury under controlled biological conditions.
Mechanistic Discovery	PPARalpha signaling and organ-axis mechanisms	ELEHAT investigates whether PPARalpha signaling and related nuclear receptor pathways mediate PFAS and ethanol interactions, including hepatic responses and extrahepatic mechanisms involving the gut-liver and adipose-liver axes.
Human Translational Relevance	Humanized PPARalpha mouse models	Because PFAS responses can differ across species, ELEHAT uses humanized PPARalpha transgenic mouse models to evaluate whether experimental findings are relevant to human liver biology.
Human Primary Hepatocytes	Human cell-based validation through collaboration	ELEHAT will incorporate human primary hepatocyte studies through collaboration with a senior colleague at the University of Louisville. These studies will help evaluate whether PFAS and alcohol-related molecular responses observed in animal models occur in human liver cells.
Structural Diversity	PFOS, PFOA, and additional PFAS classes	ELEHAT examines whether structurally distinct PFAS chemicals produce similar or divergent biological effects when combined with alcohol exposure.
Intervention and Prevention	Exposure reduction and mitigation strategies	ELEHAT explores strategies such as dietary fiber-based interventions to reduce PFAS burden and mitigate PFAS-alcohol hepatotoxic interactions.

Current Projects

Human PFAS Exposome in Alcohol-Associated Hepatitis: Measuring PFAS exposure biomarkers in de-identified plasma samples from patients with alcohol-associated hepatitis of varying severity.
PFAS-Alcohol Reverse Translation Models: Developing experimental mouse models to test whether PFAS exposures modify alcohol-induced liver injury.
PPARalpha Mechanisms in PFAS-Ethanol Interactions: Investigating the role of PPARalpha signaling in mediating hepatic and extrahepatic responses to combined PFAS and alcohol exposure.
Humanized PPARalpha Translational Models: Using humanized PPARalpha transgenic mice to assess species-relevant mechanisms of PFAS-alcohol toxicity.
Human Primary Hepatocyte Studies: Using human primary hepatocytes through collaboration with a senior colleague at UofL to test human-relevant cellular mechanisms of PFAS and alcohol co-exposure.
Structural Diversity of PFAS Toxicity: Comparing the biological effects of structurally distinct PFAS, including PFOS and PFOA, in alcohol-associated injury models.
Gut-Liver and Adipose-Liver Axis Studies: Defining how PFAS and ethanol co-exposure disrupts intestinal barrier integrity, WAT metabolic function, inflammation, lipid metabolism, and systemic metabolic signaling.
Intervention Studies: Exploring strategies such as dietary fiber-based interventions to reduce PFAS burden and mitigate PFAS-alcohol hepatotoxic interactions.

Team

Subheaders as needed for roles etc.

Principal Investigator

Frederick A. Ekuban, PhD
Assistant Professor of Medicine
Division of Gastroenterology, Hepatology, and Nutrition
University of Louisville School of Medicine

Research focus: Environmental hepatology, toxicology, PFAS-alcohol interactions, alcohol-associated liver disease, brain-liver axis, gut-liver axis, adipose-liver axis, and translational liver disease research.

Email: Frederick.ekuban@louisville.edu

Research Technician

Adrian Centers, MS

Trainees and Students

ELEHAT Summer Scholars
Undergraduate research trainees participate in hands-on laboratory training, molecular biology, qPCR, data analysis, literature review, and scientific presentations.

Jaysee McNabb (jasey.mcnabb@louisville.edu)

Addison Wiggam (addison.wiggam@louisville.edu)

Inas Saad (inas.saad0811@gmail.com)

Current student projects include:

PFOA and ethanol effects on intestinal barrier integrity and ileal injury
PFOA and ethanol effects on white adipose tissue function and metabolic signaling

Collaborators

Collaborating faculty and research partners:

Dr. Jennifer Schlezinger (Boston University)
Dr. Dhimiter Bello (University of Massachusetts, Lowel)
Dr. Jessica Hartman (Medical University of South Carolina)
Dr. Xiang Zhang (University of Louisville)
Dr. Michael Merchant (University of Louisville)
Potential areas of collaboration include hepatology, toxicology, environmental health, alcohol research, clinical liver disease, metabolomics, microbiome research, and biostatistics.

Recent Publications

Ekuban FA, et al. Perfluorooctane sulfonate exposure and alcohol-associated liver disease severity in a mouse chronic-binge ethanol feeding model. Toxicol Sci. 2025. PubMed PMID: 40347464; PubMed Central PMCID: PMC12329793
Beier JI, Luo J, Vanderpuye CM, Brizendine P, Muddasani P, Bolatimi O, Heinig SA, Ekuban FA, Siddiqui H, Ekuban A, Gripshover TC, Wahlang B, Watson WH, Cave MC. Environmental Pollutants, Occupational Exposures, and Liver Disease. Semin Liver Dis. 2025
Publication areas include:
PFAS and alcohol-associated liver disease
Environmental pollutants and liver injury
Nuclear receptor signaling and metabolic disruption
Toxicant-associated steatotic liver disease
Translational environmental hepatology

1. Mission Statement

Our mission is to bridge environmental exposure science and liver disease biology by identifying how pollutants and lifestyle factors interact to influence liver disease risk, progression, and prevention.

2. Research Vision

ELEHAT seeks to advance a new framework in liver disease research: environmental exposures are not passive background variables, but active disease-modifying factors that may help explain differences in susceptibility, severity, and outcomes among individuals with similar lifestyle or metabolic risk factors.

3. Training and Mentorship

ELEHAT is committed to training students and early-career scientists in rigorous, hypothesis-driven biomedical research. Trainees gain experience in laboratory techniques, experimental design, data analysis, scientific writing, and professional development.

4. Opportunities for Students

Students working with ELEHAT may gain experience in:

Molecular biology techniques, including RNA extraction, cDNA synthesis, and qPCR
Animal model-based toxicology studies
Histology and tissue analysis
Data analysis and figure preparation
Literature review and scientific communication
Environmental health and liver disease research

No prior research experience is required for some training opportunities. Curiosity, motivation, attention to detail, and willingness to learn are essential.

5. Research Approach

ELEHAT uses an integrated research strategy that includes:

Mouse models of alcohol-associated liver injury
Environmental pollutant exposure models
Cell culture systems
Gene expression analysis
Transcriptome analysis
Protein and biochemical assays
Histology
Metabolomics and exposure biomarker approaches
Human translational studies

6. Contact / Join the Team

Students, trainees, collaborators, and community partners interested in ELEHAT research are encouraged to contact Dr. Frederick A. Ekuban.

Email: Frederick.ekuban@louisville.edu
Phone: 502.852.4108
Location: Clinical and Translation Research Building (CTRB 514A),

University of Louisville School of Medicine, Louisville, Kentucky