Hepatology: Molecular Mechanisms and Targets in liver carcinogenesis
“The knowledge of the molecular mechanisms that occur in liver disease and the identification of new therapeutic targets for the generation of effective treatments, alone or in combination with existing ones, is a pressing need in the field of Hepatology.”
DR. MAITE GARCIA FERNÁNDEZ DE BARRENA RESEARCHER. HEPATOLOGY: MOLECULAR MECHANISMS AND TARGETS IN LIVER CARCINOGENESIS RESEARCH GROUP
All activities proposed in the Research Group include an interdisciplinary approach, promoting the integration of omics technologies to understand the biological basis of disease. With carefully selected patient samples and clinically relevant experimental models, we implement new technological developments and modeling techniques for the processing of massive data and development of new therapeutic approaches. The socio-economic, sociological, behavioral and environmental factors that contribute to the development of these severe liver diseases are also inherent to the nature of our projects, as we address the study of epigenetics, i.e. the gene-environment interactions that lead to the development of the pathological phenotype.
To this end, we combine innovative experimental approaches with the application of new informatics techniques, new data generation systems and AI processing techniques. Clinical and translational research are the pillars of our research, which is evidenced by the experience of the researchers involved, including close national and international collaborations with basic biomedical scientists, clinical scientists: internists, oncologists, surgeons and pathologists, as well as the participation of the industrial sector.
This group is integrated in the Cancer Center Clínica Universidad de Navarra.
Dr. Maite García Fernández-Barrena
GROUP LEADER
| +34 948 194 700 | Ext. 81 4006 | |
| magarfer@unav.es | |
| Research profile |
Oncology research integrated in the
Cancer Center Clinica Universidad de Navarra
Objectives of the Hepatology: Molecular Mechanisms and Targets in liver carcinogenesis Research Group
Development of omics technologies.
They constitute the instrumental basis of our research and, more specifically, in personalized health, since our study starts from patient samples to clinically relevant experimental models.
Development of new molecules as therapeutic areas.
In them we evaluate new epigenetic inhibitors and other small molecules identified as being of special relevance in liver pathologies for which there are no effective treatments available. All these therapeutic strategies are evaluated individually or in combination with existing therapies.
Description of a part of the human interactome
And dissection of its molecular connection networks, such as the etiological basis and pathophysiological processes involved in carcinogenesis. Our studies will contribute to the ultimate goal of developing the basis for personalized medicine, a strategy whose challenge is to treat the individual more effectively rather than just treating the disease.
HEPATOCELLULAR CARCINOMA
It is growing steadily, underscoring the urgent need to develop more effective and personalized therapies.
The burden of hepatocellular carcinoma (HCC), the most common form of liver cancer, is steadily increasing due to the worldwide rise in obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is replacing viral and alcohol-related liver injury as the most common cause of chronic liver disease in developed countries, affecting up to 30% of the general population. MASLD encompasses a spectrum of histologic changes ranging from simple steatosis to concomitant inflammation and cellular swelling, which defines metabolic dysfunction-associated steatohepatitis (MASH). A critical question that remains unanswered is why certain patients progress to severe symptomatic states, while a significant number do not. Similarly, the mechanisms underlying the progression from MASH to HCC in patients with or without cirrhosis are still not well understood.
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, with an increasing incidence due to the rise of these factors.
Likewise, other types of liver tumors, such as cholangiocarcinoma, an aggressive type of bile duct cancer, or hepatoblastoma, the most common liver cancer in childhood, especially in children under five years of age, have an increasing incidence.In all of them, despite advances in their diagnosis and treatment, the choice of effective treatments is particularly complicated in advanced stages, due to their resistance to many conventional treatments and the limited efficacy of the available options, underscoring the urgent need to develop more effective and personalized therapies.
Lines of research
Genetic and epigenetic processes must operate in a coordinated manner to ensure differentiated cellular functioning and homeostasis of the organism through functional and precise regulation of gene expression. Disruption of these regulatory mechanisms leads to accumulation of lesions and loss of cellular identity, processes associated with the progression of chronic liver disease and the development of liver tumors.
Objectives:
- Identification of altered epigenetic mechanisms that are essential contributors to disease progression.
- Characterization of their molecular actions.
In both chronic liver diseases and the development of liver tumors, decisive changes occur in the microenvironment. Therefore, understanding not only the hepatocyte compartment, but also that composed of immune system cells (macrophages, lymphocytes, neutrophils) together with hepatic endothelial and stellate cells, is fundamental if we want to deepen the development of new effective therapeutic strategies.
Objectives:
Development of clinically relevant experimental models of liver disease: models of acute and chronic liver damage, liver regeneration, metabolic, liver carcinogenesis models (HCC, CCA, HB).
The treatment of advanced hepatocellular carcinoma (HCC) has improved significantly with the advent of immune checkpoint inhibitors (ICIs). However, many patients still exhibit innate or acquired resistance to ICI-based therapies. Therefore, new therapeutic strategies are needed to combat this resistance and increase their effectiveness.
Objectives:
Our research Has identified promising epigenetic targets for the treatment of liver cancer (such as histone methyltransferase G9a). We conducted experiments to evaluate the effectiveness of specific inhibitors of key epigenetic targets, such as G9a, both in vitro and in vivo, and their possible combination with immune checkpoint inhibitors (ICIs).
Meet the research team
Scientific activity of the Hepatology: Molecular Mechanisms and Targets in liver carcinogenesisesearch group
Latest scientific publications
- Safe and successful gut-restricted adsorbent strategy against cirrhosis and acute-on-chronic liver failure Oct 26, 2024 | Magazine: Gut
- Sweet dreams could be made of this: carbohydrate-responsive element-binding protein (ChREBP) as a target for hepatocellular carcinoma therapy Sep 18, 2024 | Magazine: Molecular Oncology
- Comprehensive analysis of epigenetic and epitranscriptomic genes' expression in human NAFLD Nov 15, 2023 | Magazine: Journal of Physiology and Biochemistry
- Frontiers in fatty liver: recent advances in pathogenic mechanisms, assessment of patients' prognosis and pharmacotherapy : MASLD: new pathogenic mechanisms, risk assessment tools and drug therapies Nov 15, 2023 | Magazine: Journal of Physiology and Biochemistry