The path of cancer evolution dictates the tumor response to therapy and creates unique vulnerabilities that represent therapeutic opportunities. Based on this concept, Lowe’s Lab is developing powerful methods to follow the behavior of tumor-initiating cells in normal tissues in living mice. Moreover, using inducible RNA interference systems, they suppressed the function of different genes in vivo in a stable and reversible manner in order to characterize cancer drivers and the dependencies they create. Fascinating results were shown on the reversibility of gastrointestinal malignancies phenotypes turning on and off the function of specific factors.
The formation of digits during development is a high regulated process coordinates by the Hoxd genes. By analyzing the chromosome conformation and Hox transcriptional regulation during the process, Duboule’s Lab showed that the active part of the Hoxd gene cluster contacts with several regulatory islands within the centromere. Interestingly, a similar regulatory organization was found during the development of external genitals. Moreover, a similar situation is observed at the HoxA locus. Denis Duboule discussed about potential common mechanisms for Hox genes transcriptional regulation in different contexts.
The liver is an organ with a high regeneration potential and Markus Grompe is one of the most excellent scientists working in this field. Using lineage tracing mice, he tracked hepatic stem cells that are suppose to product oval cells during severe liver injury. Surprisingly, no oval cells derived from the differentiation of hepatic stem cells were found in presence of different liver injuries. On the other side, mature hepatocytes seem to undergo a reprogramming process forming hepatocyte-derived progenitors that in turn can differentiate to become fully functional hepatocytes. This results suggest that a reprogramming process of mature hepatocytes, and not the classical differentiation of the existing hepatic stem cells, mediates the regenerative response to liver injury providing new fascinating insights into the mechanisms of tissue regeneration.
CRG Symposium 2014