Where Ideas grow
Differentiation & Cancer

ABOUT

Our aim is to understand the impact of regulatory mechanisms, transcriptional and post-transcriptional, in cancer initiation and progression. We focus mainly on the mechanisms that drive differentiation switches, which constitute the starting point of a significant number of carcinogenic processes, namely in the GI tract. We adopt an integrative approach using clinical specimens, cellular systems and animal models to identify key molecular events and biomarkers that may contribute to understand the biology of cancer and may be translated to patient care. 

 

RESEARCH

 

We have identified CDX2 as a prognostic marker in gastric cancer and in colon cancer where it also predicts therapy response. We have also identified SOX2 as an additional biomarker in the context of CDX2 loss of expression, contributing to further stratify patients into groups with different therapy responses, which has important implications in clinical decision-making in the context of colorectal cancer clinical practice. We generated a CDX2 knock-out cellular model, using a genome-editing strategy, that was characterized in depth regarding CDX2 expression modulation and transcriptomic alterations. With this strategy we identified new CDX2 targets and currently we are studying their potential relevance as cancer biomarkers.

We have identified a post-transcriptional regulatory system involved in intestinal stem cell identity and cancer.

We characterized MUC16 glycoforms and new monoclonal antibodies were produced by the group. Studies in ovarian carcinomas extended our knowledge on mucin glycoforms that are relevant and can improve current biomarkers in clinical use. We have been studying the interaction of MUC16 with mesothelin, using the cellular assay “mesothelial clearance”, to understand the role of these proteins in peritoneal metastization of ovarian cancer.

 

Left. Schematic representation of the transformation of a gastric gland into a metaplastic gland with intestinal phenotype. Right. Intestinal metaplasia stained by immunohistochemistry for MUC2 (red) and CDX2 (broen), two key markers of this type of lesion.