Funding Programme
National Recovery and Resilience Plan (NRRP) – Component C9: Support for the Private Sector, Research, Development and Innovation, Investment I8: Development of a Programme to Attract Highly Specialized Human Resources from Abroad for Research, Development and Innovation Activities.

Project Title: TRANSLATIONAL RESEARCH TARGETING FIBROSIS REGRESSION, REVERSAL OF ENDOTHELIAL DYSFUNCTION, AND HEPATOCYTE REGENERATION IN ADVANCED LIVER DISEASES – 3RE-VALID

Contract Number: 760064/23.05.2023

Project Code: 36/14.11.2022

The total project budget amounts to RON 7,760,000, consisting of RON 7,000,000 PNRR funding and RON 760,000 VAT.

Project Duration: 36 months (01 July 2023 – 30 June 2026)

Project Directors

Prof. Dr. Jaime Genover Bosch (†)

Coordination Period: 01.07.2023 – 15.07.2025

• Emeritus Professor of Medicine, University of Barcelona, Spain;
• Guest Professor of Medicine, Department of Biomedical Research, University of Bern and University Clinic for Visceral Surgery and Medicine, Inselspital Bern, Switzerland;
• President of the International Baveno Cooperation Consortium;
• Doctor Honoris Causa of the “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca.

Prof. Dr. Jaime Bosch was one of the leading figures in global hepatology, whose scientific and academic contributions had a remarkable impact on the advancement of research and clinical practice in the field of liver diseases.

Prof. Dr. Dominique Charles Valla

Coordination Period: 01.11.2025 – 30.06.2026

• Internationally renowned physician and researcher, former Director of the Department Hospitalo-Universitaire UNITY and Professor of Hepatology and Gastroenterology at Université Paris 7 – Denis Diderot;
• Prof. Dominique Valla is widely recognized for his outstanding contributions to the fields of portal hypertension and vascular liver diseases. Since 1976, he has published more than 350 scientific articles, including over 100 dedicated to vascular liver diseases and more than 50 focused on portal hypertension and its complications;
• His work has significantly increased awareness of the impact of vascular liver diseases on patient survival and quality of life. He also led the establishment of France’s National Reference Center for Vascular Liver Diseases and is co-founder of the European and international VALDIG (Vascular Liver Disease Group) network.

Implementation Location

The project is implemented within the “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, at the following locations:

• Medical Discipline III, 19–21 Croitorilor Street, Cluj-Napoca;
• DEPCDI, 4 Louis Pasteur Street, Cluj-Napoca;
• MedFuture Research Center for Advanced Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca.

Project Description

To address current challenges in the field of advanced liver diseases, the 3RE-VALID project aims to develop a modern translational research platform dedicated to liver healing and regeneration processes.

Using both in vitro and in vivo experimental models, the project investigates the mechanisms involved in liver fibrosis regression, restoration of hepatic sinusoidal endothelial function, and hepatocyte regeneration.

The integration of data through systems biology approaches enables a comprehensive understanding of these processes and facilitates the identification of innovative therapeutic targets. Furthermore, through the multi-omic evaluation of circulating extracellular vesicles, the project seeks to identify predictive biomarkers of liver healing.

In parallel, a prospective registry and biobank dedicated to advanced liver diseases are being developed to support future research validation and facilitate the translation of research findings into clinical practice.

General Objective

The 3RE-VALID project aims to develop a translational research platform in the field of advanced liver diseases, focusing on liver fibrosis regression, reversal of portal hypertension and endothelial dysfunction, as well as stimulation of liver regeneration and recovery of hepatic function.

Specific Objectives

1. To investigate and understand the mechanisms involved in liver fibrosis regression, reversal of portal hypertension, recovery of sinusoidal endothelial function, and hepatocyte regeneration.
2. To evaluate the contribution of simvastatin, aspirin, and rivaroxaban to liver fibrosis regression, reduction of portal hypertension, and stimulation of liver regeneration using multi-omics and systems biology approaches.
3. To establish a state-of-the-art basic research laboratory, together with a prospective biobank and a regional registry dedicated to liver cirrhosis and portal hypertension.
4. To recruit and train a new generation of researchers and PhD students to ensure the sustainability of the research activities developed within the project.

Main Activities

1. Project initiation and management;
2. Investigation of the mechanisms underlying liver fibrosis regression and portal hypertension;
3. Testing the effects of pharmacological interventions on disease regression;
4. Development of the biobank and collection of biological samples;
5. Analysis and interpretation of experimental data;
6. Dissemination and exploitation of research results..

Result Indicators

The project committed to achieving the following outcome indicators:

• Publication or acceptance for publication of three scientific articles in journals indexed in the Science Citation Index Expanded (SCIE), Social Sciences Citation Index (SSCI), or Arts & Humanities Citation Index (AHCI), ranked in the first quartile (Q1) of the relevant Web of Science category;
• Submission of at least one project proposal reaching the funding threshold within Horizon Europe competitions;
• Submission of at least three proposals in national research, development, and innovation competitions.

Project Team

The project brought together a multidisciplinary team composed of experienced researchers, postdoctoral researchers, PhD students, technicians, and research assistants.

Project Directors

• Prof. Dr. Jaime Bosch
• Prof. Dr. Dominique Charles Valla

Experienced Researchers

• Associate Professor Bogdan-Dumitru Procopet, MD, PhD
• Research Scientist III, Dr. Horia Octavian Ștefănescu

Postdoctoral Researchers

• Luciana-Mădălina Gherman
• Oana-Maria Nicoară-Fârcău
• Andra Ciocan
• Cristina-Alexandra Ciocan
• Diana Cecilia Bica
• Iulia Minciuna
• Petra-Cecilia Fischer
• Alexandru-Leonard Alexa
• Ioana Ecaterina Pralea
• Cristian Radu Tefaș

PhD Researchers

• Iulia Minciuna
• Maria Buziaș
• Cornelia Tăluță-Băieș
• Mădălina-Gabriela Țaru
• Oana-Maria Nicoară-Fârcău
• Vlad Țaru
• Andreea Fodor
• Mina-Dana Ignat
• Edina Seulean
• Teodora Frățilă

Research Support Staff

• Teodora-Maria Toadere – Technician
• Elisa Marziali – Technician
• Dragoș-Lucian Hodor – Research Assistant
• Andreea Teodorescu – Research Assistant

Research Infrastructure Developed

Within the project, modern research facilities were established and equipped to support experimental and translational research activities in the field of advanced liver diseases:

• Experimental Hepatic Hemodynamics Laboratory;
• Liver Imaging Laboratory;
• Tissue and Biological Sample Biobank;
• Advanced facilities for liver ultrasound and elastography;
• Experimental platform for animal models of liver fibrosis.

Main Results

The implementation of the project led to significant scientific and infrastructural achievements:

• Development and validation of an experimental model of liver fibrosis regression;
• Implementation of advanced hemodynamic assessment and imaging technologies;
• Establishment of a biobank dedicated to liver disease research;
• Identification of proteomic markers associated with liver fibrosis regression;
• Demonstration of reduced inflammation and liver stiffness following cessation of toxic injury;
• Development of a comprehensive experimental database for future studies on the reversibility of advanced liver diseases.

Scientific Publications

Within the project, several articles were published or accepted for publication in prestigious international journals:

1. Inflammasomes in Chronic Liver Disease: Hepatic Injury, Fibrosis Progression and Systemic Inflammation
   Journal of Hepatology, Volume 81, Issue 5, November 2024, pp. 895–910
   Authors: Vlad Țaru, Gyongyi Szabo, Wajahat Mehal, Thomas Reiberger
2. Platelet Proteomics: A Glimpse Into Metabolic Dysfunction-Associated Steatotic Liver Disease Pathogenesis in Hepatology Research
   Authors: Iulia Minciuna, Maria Iacobescu, Ioana Rusu, Oana Nicoară-Fârcău, Petra Fischer, Andreea Maria Soporan, Ioana Ecaterina Pralea, Horia Ștefănescu, Cristina Adela Iuga, Bogdan Procopet
3. Impact of Underlying Portal Hypertension on Severity and Course of Acute-on-Chronic Liver Failure
   Published in Liver International
   Authors: Vlad Țaru, Georg Kramer, Benedikt S. Hofer, Nina Dominik, Lorenz Balcar, Mathias Schneeweiss-Gleixner, Bogdan Procopet, Michael Trauner, Mattias Mandorfer, Philipp Schwabl, Thomas Reiberger, Benedikt Simbrunner
4. Liver Disease in Common Variable Immunodeficiency: Current Evidence and Knowledge Gaps
   Published in International Journal of Molecular Sciences
   Authors: Irena Nedelea, Oana Nicoară-Fârcău, Bogdan Procopet, Horia Ștefănescu, Corina Radu, Radu Balan, Ana-Maria Fit, Ioana Rusu, Diana Deleanu
5. Endoscopic Ultrasound versus Direct Transjugular Portal Pressure Gradient in Patients Receiving TIPS: Influence of Portal Vein Thrombosis
   Published in Gastroenterology Report, Volume 14
   Authors: Irina Dragomir, Cristina Pojoga, Claudia Hagiu, Sorana D. Bolboacă, Alexandru Alexa, Oana Nicoară-Fârcău, Petra Fischer, Horia Ștefănescu, Bogdan Procopet, Andrada Seicean

Projects Submitted in National Competitions

The results and expertise developed within the project contributed to the submission of several research proposals in national funding competitions:

1. PN-IV-P1-PCE-2023-0837
   Title: Endothelial Dysfunction and Novel Therapeutic Targets in Porto-Sinusoidal Vascular Disease
   Project Director: Associate Professor Bogdan Procopet, MD, PhD
2. PN-IV-P2-2.1-TE-2023-0168
   Title: Renal Ultrasound Elastometry and Urine Metabolomics: Precise Diagnostic Biomarkers for Acute Kidney Injury in Cirrhosis
   Role: Research team member – Horia Ștefănescu
   Status: Funded project
3. PN-IV-RU-SC-PD-2026
   Title: Integrating Splenic Stiffness, Coagulation Biomarkers and Radiomics into a Prediction Model for Portal Hypertension in Portal Vein Thrombosis
   Project Director: Dr. Oana Nicoară-Fârcău
4. PN-IV-P1-PCE-2026-1036
   Title: Porto-Sinusoidal Vascular Disorder as a Complication of Chemotherapy in Colorectal Cancer: Mechanism, Prognosis and Potential Therapeutic Target (CHEMOVASC)
   Project Director: Associate Professor Bogdan Procopet, MD, PhD
5. PN-IV-P2-2.1-PD-2026-1393
   Title: FLOW-PVT: From Flow to Clot—Decoding the Biology of Portal Vein Thrombosis to Personalize Management after Liver Transplantation
   Project Director: Dr. Iulia Minciuna
6. PN-IV-P2-2.1-PD-2026-0595
   Title: Targeting Fibroblast-Mediated Chemoresistance in Mammary Cancer Using a Spontaneous Canine Model
   Project Director: Dr. Mădălina Gherman
7. PN-IV-P2-2.1-PD-2026-0256
   Title: Integrated Characterization of Neutrophil Dysfunction and Innate Immune Biomarkers in Cirrhosis-Associated Immune Dysfunction (CIRRUS)
   Project Director: Dr. Petra Fischer
8. PN-IV-P1-PCE-2026-0346
   Title: RESOLVE_ALD: Paired Liver–Spleen Stiffness Model to Predict Alcohol-Related Liver Disease Trajectory by Dissociating Irreversible Fibrosis from Reversible Injury
   Project Director: Dr. Horia Ștefănescu

Horizon Europe Projects

Within the European Rare Disease Research Alliance (ERDERA) call, the following project proposal was submitted: RESOLVE-ID – Resolving Uncertain and Complex Genetic Variants in Patients with Primary Antibody Deficiencies and Immune Dysregulation to Achieve Diagnostic Clarity through Functional Genomics, Multi-Omics and Systems Biology

Project Impact

The 3RE-VALID project contributes to strengthening advanced biomedical research in Romania and to the development of novel therapeutic strategies for patients with advanced chronic liver diseases.

The project outcomes support the identification of predictive biomarkers and new therapeutic targets, facilitating the advancement of personalized medicine and improving the prognosis of patients with liver fibrosis and portal hypertension.

Keywords

Liver Fibrosis • Portal Hypertension • Liver Regeneration • Endothelial Dysfunction • Proteomics • Translational Research • Biobank • Precision Medicine • PNRR • Hepatology

Information related to the project can also be found at the following address: https://lirec-ro.lirec-ro.workers.dev/revalid/

PNRR. Finanțat de Uniunea Europeană – UrmătoareaGenerațieUE
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