Biotrack

Role of Angiogenesis in Liver Diseases

REF: PD 33
Principle investigator:
Mercedes Fernandez
Contact details:

mercefernandez(ELIMINAR)@ub.edu

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Research framework

Our laboratory investigates the role of angiogenesis, that is, the formation of new blood vessels, in the pathophysiology of portal hypertension and chronic liver diseases, which affect millions of human beings all over the world. Much of our work is devoted to define the therapeutically important roles of angiogenesis in chronic liver disease, giving particular attention to understand the molecular and cellular mechanisms that govern the control of the angiogenic process. This is essential to fully elucidate the pathological functions of angiogenesis, and to facilitate the identification of new and more effective therapeutic strategies, which, by inhibiting or attenuating angiogenesis, could be potentially useful to reduce the morbility and mortality of patients suffering from advanced portal hypertension and chronic liver disease. This is very important since the therapeutic options for these diseases are limited.

Our approach is multidisciplinary and employs a variety of animal models of liver diseases in rat and mouse, genetically engineered mouse models, established mammalian cell lines, samples of liver tissue from patients with liver disease, in vivo hemodynamic studies in animals, in vitro cell culture studies, tissue histology and immunohistochemistry, and biochemical, cellular and molecular biology strategies.

Our work has been published in:

  • Gastroenterology 126:886-94 (2004)
  • Journal of Hepatology 43:98-103 (2005)
  • Journal of Hepatology 44:1033-9 (2006)
  • Hepatology 46:1208-18 (2007)
  • Gut 56:560-4 (2007)
  • Journal of Cellular and Molecular Medicine 12:1690-9 (2008)
  • Hepatology 49:1245-1256 (2009)
  • Journal of Hepatology 50:296-305 (2009)
  • Journal of Hepatology 50:604-620 (2009)
  • Journal of Hepatology 52:529-539 (2010)
  • Journal of Hepatology 53:558-567 (2010)
  • American Journal of Physiology 302:G1191-8 (2012)
  • Journal of Hepatology 56 (Suppl 2): S53 (2012)

In the course of our research, we have demonstrated that angiogenesis is a crucial pathological hallmark of chronic liver disease, which contributes to the development and maintainance of portal hypertension, hyperdynamic splanchnic circulation, and postosystemic collateralization, and is also closely linked to fibrogenesis and inflammation in the cirrhotic liver. Our studies have also started to delineate the regulatory mechanisms underlying the pathological formation of new blood vessels in portal hypertension and liver cirrhosis, highlighting that the control of neovessel formation, through an antiangiogenic treatment, could be a promising, novel strategy with therapeutic benefit for patients with chronic liver disease.

Keywords

Angiogenesis, cirrhosis, portal hypertension, blood vessels, therapeutic targets.

Main Challenges

We seek a highly motivated, creative and bright individual, to work on a project that involves both basic and translational studies on angiogenesis in portal hypertension and chronic liver disease. The main challenges of our research will be to decipher the molecular and cellular regulatory mechanisms of angiogenesis during portal hypertension and hepatic cirrhosis, and to experimentally evaluate new therapeutic approaches for the treatment of these diseases.

The knowledge derived from the proposed studies will directly impact our understanding of the angiogenesis´ role in chronic liver diseases, which are a leading cause of death and hepatic transplant worldwide, and may also open up possibilities for developing new and more effective therapeutic strategies for the treatment of patients suffering from chronic diseases of the liver.

The successful candidate will contribute to the design and planning of experiments in relation to the project and will be responsible for the execution of the studies, working closely with physiologists, molecular biologists and protein biochemists in our lab and other departments.

Experience with animal models of disease, cellular and molecular biology and protein biochemistry is a plus.

Team strategic objective in IDIBAPS

The gaining of in-depth knowledge of the mechanisms underlying portal hypertension (the main complication of liver diseases) and development of new treatments for this syndrome, and new non-invasive assessment techniques.

In particular, research in our laboratory focuses on the implication and regulation of angiogenesis in the physiopathology of portal hypertension and chronic liver diseases.

(Read eligibility criteria)