What we do …

To decipher the major disease-relevant pathways in the progression from liver steatosis to fibrosis and liver cancer

Liver cancer is among the most lethal and prevalent cancers worldwide, and the second most common cause for cancer-related death. In contrast to other cancers, its incidence is rising dramatically, and is predicted to increase even more in the coming years mainly due to the global epidemic of obesity/overweight, which has become a major socioeconomic challenge and strong risk factor for liver cancer. There is also an urgent need for development of novel therapeutic strategies to treat liver cancer. And for that it is essential to decipher mechanisms underpinning the detrimental impact of obesity on the progression of chronic liver disease, from simple steatosis to fibrosis and liver cancer, which are mostly still unknown. This is a major goal of our group.

To explore the pathogenic mechanisms underpinning the detrimental impact of obesity in chronic liver disease

Over the last decades, obesity and its consequences have become a major health problem. Worldwide, more than 1 billion adults are overweight. The worst is that obesity does not only affect adults but also children. Obesity impacts on chronic liver disease by inducing liver steatosis and steatohepatitis, and by modifying the properties of intestinal microbiota and barrier and the functionality of visceral fat depots. Despite the clinical importance of the link obesity-liver disease, our understanding of the mechanisms underlying this relationship is extremely limited. This knowledge is crucial for advancements in treatment strategies for patients suffering from chronic liver disease. This is a major goal of our group.

To understand the function and regulation/dysregulation of angiogenesis in chronic liver disease

Angiogenesis is a hallmark of chronic liver disease that plays a major role within the liver, promoting inflammation, fibrogenesis and tumorigenesis, and also outside the liver, in splanchnic organs, contributing to the development of gastroesophageal varices and portal hypertension, which are clinically relevant complications of chronic liver disease. Therapeutic targeting of angiogenesis has been proposed as a promising strategy for chronic liver disease, including liver cirrhosis and liver cancer. However, the clinical benefit of antiangiogenic drugs is restricted because of significant adverse effects, including collapse of normal vasculature, vascular leakage and bleeding, as exemplified in patients with hepatocellular carcinoma and cirrhosis. Most of these limitations arise from the fact that current anti-angiogenic approaches are not selective for pathological neovessel production, but instead inhibit also physiological angiogenesis required for vascular homeostasis of healthy vessels and for processes like wound healing and tissue repair. Deciphering the molecular and cellular mechanisms that regulate/dysregulate angiogenesis in chronic liver disease is therefore critical to achieve specific inhibition of pathological neovascularization with beneficial therapeutic effects. This is a major goal of our group.

To apply our knowledge and research discoveries on the fundamental cell biology/pathophysiology of liver disease to the comprehension, prevention or treatment of human pathologies

Chronic liver diseases are highly prevalent and associated with a high and dramatically increased burden worldwide. Despite that, development of new therapeutics remains stagnant. Liver transplantation currently represents the only chance of long-term survival for patients with chronic liver disease, but the availability of appropriate donor tissue is limited, and the procedure is highly expensive, necessitating a search for alternatives. Therefore, it is urgent to develop new strategies for diagnosis, prevention and treatment of chronic liver diseases. This is a major goal of our group. To this end, our team has established a working, highly collaborative and multidisciplinary relationship with world leading basic scientists, clinicians and bioinformaticians, with whom we have a high degree of connectivity and complementarity. This synergistic relationship allows us to achieve better outcomes and better opportunities to discover new druggable targets and innovative therapies for the treatment of chronic liver disease.