About This Project
MASLD, nonalcoholic fatty liver disease, affects up to 30% of the population. We hypothesize that exposure to bisphenols (BPA, BPF, BPS) accelerates hepatic epigenetic aging, contributing to disease severity. Using DNA methylation clocks, histone profiling (Cut&Run), and transcriptomics in liver, adipose, and gut tissues, we will explore this relationship and assess whether a BPA-free diet can reverse these changes and reduce disease burden.
Ask the Scientists
Join The DiscussionWhat is the context of this research?
This project investigates how exposure to bisphenol A (BPA) and its analogues contributes to the development and progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a growing global health concern. It focuses on the role of hepatic epigenetic aging as a potential mechanism linking environmental exposure to metabolic dysfunction. The study uses advanced molecular techniques—including DNA methylation analysis, gene expression profiling, and histone modification mapping—to identify early epigenetic changes associated with disease severity. Additionally, it evaluates whether a BPA-free diet can reverse harmful epigenetic signatures and improve liver health. The project addresses an urgent need to understand the molecular basis of MASLD in the context of environmental pollutants and aging, with the aim of identifying biomarkers and preventive strategies.
What is the significance of this project?
This project addresses a critical gap in understanding how environmental pollutants like bisphenols contribute to the progression of MASLD through epigenetic mechanisms. By integrating DNA methylation, histone modifications, and transcription factor analysis, it offers a comprehensive view of liver aging and metabolic dysregulation. The inclusion of peripheral blood analysis aims to identify non-invasive biomarkers, enhancing early detection and risk stratification. Additionally, evaluating the impact of a BPA-free diet provides actionable insights for prevention. The project’s findings could lead to innovative diagnostic tools and personalized therapeutic strategies, with broad implications for public health, particularly in populations affected by obesity and metabolic disease.
What are the goals of the project?
The goal is to assess how exposure to bisphenols influences hepatic epigenetic aging and contributes to the development and progression of MASLD. Using liver biopsies and PBMCs from 80 bariatric surgery patients (aged 25–65, balanced by sex and MASLD severity), we will quantify DNA methylation via EPIC arrays, evaluate histone modifications (H3K27me3, H3K4me3, H3K27ac), and analyze transcription factor binding (PPARγ, SREBP1, FOXO3) using Cut&Run. We will correlate epigenetic age acceleration with histology, metabolic markers, gender, and age. BPA, BPF, and BPS levels will be measured in urine and adipose tissue to evaluate their accumulation and association with adipocyte hypertrophy and macrophage infiltration. Gut dysfunction will be assessed via jejunal histology, gene expression (ZO-1, claudins, IL-6), and serum markers (LBP, zonulin). A BPA-free diet intervention in 40 MASLD patients will monitor compliance through dietary surveys, weekly follow-up, and urinary BPA reduction.
Budget
The proposed budget supports all critical components needed to achieve the project’s objectives. Funding a predoctoral researcher ensures continuity and execution of lab work, including DNA methylation, gene expression, and Cut&Run analyses. Consumables cover essential materials for sample collection (liver, PBMCs), processing, and molecular assays. Outsourcing services to specialized companies guarantees high-quality and reproducible data. Budget allocation for biobank storage ensures long-term sample preservation, while patenting costs protect potential discoveries.
A key component is the involvement of a predoctoral student for 3 years, Mirko, who will take on a central role in the experimental work and data analysis, while developing their doctoral thesis within a high-impact, interdisciplinary research environment. Beyond technical skills, this project provides a unique chance to contribute to cutting-edge knowledge on epigenetics, environmental health, and metabolic disease.
Endorsed by
Project Timeline
The project spans 36 months. In the first 12 months, all biological samples and baseline data will be collected. Months 12–24 will focus on epigenetic (DNA methylation), gene expression, and Cut&Run analyses. Data integration, statistical analysis, and interpretation will take place from months 24–30. The final 6 months (30–36) will be dedicated to result dissemination, manuscript preparation, and thesis development by the predoctoral researcher.
Jul 13, 2025
Project Launched
Aug 31, 2026
Completion of patient recruitment and sample collection
Mar 31, 2027
Completion of DNA methylation profiling (EPIC arrays)
May 31, 2027
Completion of gene expression analysis (RT-qPCR)
Jul 31, 2027
Completion of Cut&Run histone modification and TF analysis
Meet the Team
Team Bio
Teresa Auguet serves as the Head of Internal Medicine at the University Hospital Joan XXIII in Tarragona. She is also a Professor of Medicine at Rovira i Virgili University and Vice Dean of the Faculty of Medicine and Vice President of the Institut d'investigació Sanitària Pere Virgili. With a solid background in clinical and translational research, T.A. integrates clinical care into her scientific work. Dr Auguet will be Mirko's thesis director.
Mirko Paparella
Mirko Paparella is a biologist born in Rome in 1996. Orphaned at a young age and raised in a challenging environment, he found in science not only a path to personal growth but also a purpose. Despite the obstacles, he earned both a Bachelor's and a Master's degree in Biology and Human Nutrition Sciences at Campus Bio-Medico University of Rome, graduating with top honors.
Driven by a strong passion for translational research, Mirko currently works as a researcher at the Institute for Bioengineering of Catalonia (IBEC) in collaboration with the Centre for Omic Sciences (Eurecat), as part of the EU-funded ADGUT project. His work focuses on studying the gut–microbiota–brain axis in Alzheimer’s disease, combining genomic, transcriptomic, and epigenetic approaches.
Mirko has developed solid skills in both classical and cutting-edge molecular biology techniques, including PCR, second- and third-generation NGS, ATAC-Seq, Cut&Run, and RRBS, as well as sample preparation and omics data analysis. His previous experience also includes working on diabetes and inflammation-related projects at Campus Bio-Medico University of Rome, where he handled tissue samples, performed ELISA and Western blot, and managed clinical datasets.
Today, Mirko aspires to become a PhD student within the GEMMAIR group, under the supervision of Dr. Auguet, whose scientific vision and research line perfectly align with his personal and professional goals. Research is his true passion, and joining this project would not only be a key step in his academic path, but also the fulfillment of a lifelong dream born from perseverance, curiosity, and a deep desire to contribute to science.
Lab Notes
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