The project
The COVID-19 pandemic has underscored the close link between SARS-CoV-2 infection and cardiovascular complications, including long-lasting symptoms that may persist months after infection. Yet, the mechanisms by which the virus reaches the heart and causes enduring damage remain largely unclear.
This project addresses this gap by developing bioengineered 3D cardiac models and advanced epigenomic technologies to investigate the cellular and molecular processes underlying cardiac dysfunction and Long COVID, supporting the discovery of new therapeutic and preventive strategies.
Our mission
The project develops experimental tools to study how SARS-CoV-2 interacts with the human heart in physiological conditions. Using biofabrication, microfluidics, and epigenomic analyses, it aims to:
- Explore the main pathways of viral entry into the heart;
- Investigate indirect pathways of viral entry;
- Uncover epigenetic changes driving long-term symptoms;
- Provide models to advance cardiovascular research and therapy development.
The goal is to make invisible infection mechanisms visible and turn them into actionable knowledge for human health.
Objectives
The project’s approach is structured around two main objectives:
Understanding How SARS-CoV-2 Reaches the Heart
We aim to recreate cardiovascular milieux using bioengineered 3D cardiac models and a heart-on-a-chip system, to study the two most likely pathways:
Vascular route and Pericardial route
These models offer the opportunity to overcame the challenges that are present in in vivo models.
Analyzing Virus-Induced Epigenetic Remodeling
We employ 4fSAMMY-seq, a patented technology for studying chromatin architecture, combined with RNA-seq to identify:
deregulated genes,
changes in genome compaction,
altered cellular programs that persist even in the absence of the virus.
The goal is to elucidate the epigenetic origins of cardiovascular Long COVID.
Approach
Bioengineered 3D Cardiac Models
Cardiomyocytes derived from pluripotent stem cells (iPSC-CMs) and supporting cells (fibroblasts, pericytes, endothelial cells, and smooth muscle cells), are assambled withon 3D scaffold s allow the study of viral effects across multiple cell populations simultaneously
Heart-on-a-Chip
A microfluidic system that simulates the interaction between pericardium and myocardium, enabling observation of viral transfer from the lung environment to the heart.
Omics Technologies
4fSAMMY-seq and RNA-seq are used to map infection-induced chromatin remodeling, providing a comprehensive view of changes at both the genome and transcriptome levels
Impact
The project’s results have direct implications for understanding COVID-19–related cardiovascular disease and Long COVID:
- New 3D experimental models useful for studying the human heart.
- Identification of viral entry pathways into the heart.
- Mapping of epigenetic alterations that persist beyond infection.
- Potential for discovering new diagnostic markers and therapeutic targets.
- Tools transferable to other research on viral infections and heart diseases.
The project contributes to generating new scientific knowledge and providing tools applicable in translational research.
Consortium
Sapienza University – Department of Medical-Surgical Sciences and Biotechnology
Led by Prof. Roberto Rizzi, this unit specializes in biofabrication, 3D bioprinting, regenerative medicine, and the development of complex human tissue models. The laboratory is equipped with bioreactors, advanced bioprinting technologies, and extensive expertise in generating biomimetic systems.
Project Team
Claudia Bearzi, Senior Researcher
Salma Bousselmi, PhD Student
Nicole Fratini, PhD Student
Paola Pontecorvi, Post Doc
Fabio Maiullari, Post Doc
CNR – Institute of Biomedical Technologies (Project Partner)
Coordinated by Dr. Chiara Lanzuolo, this unit is a leader in studying chromatin architecture and epigenomic techniques. It developed 4fSAMMY-seq, a key technology for investigating chromatin structural changes in the genome.
Project Team
Valentina Rosti, Post Doc
Arianna Tisba, PreDoc fellow
Marinicla Pascale, PreDoc fellow
Together, the two groups combine bioprinting, organ modeling, microfluidics, and epigenetics into a single integrated research platform.
Insights
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