I studied Biotechnology at University of Leon (Spain) and completed my studies at VU Amsterdam (The Netherlands) as part of the ERASMUS program. As an undergrad, I performed an internship in the group of Dr. Mar Fernandez-Borja (Sanquin, The Netherlands), where I became fascinated by the beauty and challenges of cell biology research. Hereafter, I enrolled in the Master of Biomolecular Sciences at VU Amsterdam where I had the opportunity of performing two additional internships in the groups of Dr. Wilbert Zwart (NKI, The Netherlands) and Dr. Omer Yilmaz (MIT, USA).

Captivated by the concept of asymmetric cell division and stem cell niche, I decided to join Dr. Trevor Dale lab. My project aims to determine whether the cancer-inducing loss of Axin protein in the liver is mediated by changes in cell polarity.

My Project

The mammalian liver is a secretory organ that plays an important role in human physiology by assisting lipid absorption, degrading toxic compounds, regulating glucose homeostasis, and modulating the biosynthesis of plasma proteins. To efficiently integrate all these functions, the liver is organized into polygonal structural units known as hepatic lobules (Fig1). In the liver lobule, blood flows from the portal fields to a central vein through a network of sinusoids that line up the hepatocytes in branching cords of cells. 14 to 25 hepatocytes are arranged between the central vein and the portal triad. The metabolic function of these hepatocytes differs based on their position in the porto-central vein axis of the liver lobule, giving rise to three functionally distinct zones (Fig1).

Fig1. Structure of the zonated liver lobule. On the left, a three-dimensional structure of the liver organized in polygonal lobules. Blood rich in nutrients from digestion (portal vein, PV) mixes with oxygenated blood (hepatic artery, HA) and flows through sinusoids from the portal triad to the central vein. Bile produced by the hepatocytes is secreted into bile canaliculi and transported to bile ducts formed by cholangiocytes. Red and green arrows indicate the blood and bile flow in the hepatic lobule, respectively. Based on their metabolic specialization, hepatocytes can be functionally segregated in three metabolic zones (insert).

Wnt/b-catenin signaling has been proposed as key regulator of liver zonation. Genetic alterations in components of the Wnt/b-catenin signaling transduction are frequently found in human cancer. Traditionally, the oncogenic potential of these mutations have been attributed to the subsequent increase of b-catenin protein levels and transcriptional activity. Surprisingly, previous work at Dale lab has shown that loss of Axin, a negative regulator of Wnt/b-catenin frequently mutated in hepatocellular carcinoma (HCC), triggers the appearance of tumors while preserving zonal expression of b-catenin and the perivenous marker GS in the liver lobule (Feng et al., 2012). Therefore, the mechanism by which Axin loss drives oncogenesis remains an open question.

My project aims to determine whether the cancer-inducing loss of Axin in the liver is mediated by changes in cell polarity. For this aim, I am generating an in vitro system that (1) recapitulate key elements of liver zonation and (2) allows the study of hepatocyte cell division.