Fabrice Lavial Cellular reprogramming, for better or worse

The promise of cellular reprogramming

During development, stem cells differentiate into specialized cells characterized by genetic expression programs specific to each cell type. Those identities are expected to remain stable as cells divide. However, differentiation can be "erased" by using four factors (Oct4, Sox2, Klf4 and c-Myc) that act on genetic expression and give cells the characteristics of stem cells again. This process is called cellular reprogramming. We can imagine taking skin cells from a patient, reprogramming them to obtain stem cells, then programming them again into brain cells, for example. This type of process holds out tremendous therapeutic potential.

The dark side of reprogramming

These great therapeutic promises should be taken with caution. More research is necessary to understand the mechanisms and long-term consequences of reprogramming. Indeed, when carried out in animals (in vivo), reprogramming boosts the regeneration capacity of certain tissues but also causes a disease where cell multiplication is uncontrolled: cancer. Consequently, despite their revolutionary effects, the molecular mechanisms triggered by in vivo reprogramming must be understood better to avoid reaching the point where cells become cancerous. The reprogramming process has similarities with cancer, such as giving cells the ability to renew themselves and resist aging and cell death. The genes involved in both processes have received little attention, mainly due to a lack of dedicated genetic tools, yet this research will be crucial to understanding interactions between reprogramming and cancer, which have diametrically opposite effects.

A mechanism in common with the development of cancer

Impulscience grant will allow Dr. Lavial's team to answer key questions before considering therapeutic prospects using cellular reprogramming. He will compare and study the genetic expression profiles of reprogrammed cells and lung cancer cells. This will reveal the molecular program allowing cells to acquire the ability to reprogram themselves and determine the critical point at which they become cancerous. The research program’s originality lies in using mouse models developed in Dr. Lavial's laboratory that allow him to accurately control when and in which cells reprogramming and tumor growth will be triggered. That way, the team can map genetic events and predict critical moments. Researchers will be able to pinpoint which genes need to be blocked to keep the reprogrammed cells from becoming cancerous.