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Molecular mechanisms of apoptosis

During its existence, a cell may encounter various types of exogenous or endogenous stresses. A cell will react to an insult by activating molecular pathways that can either promote survival or, in the opposite, trigger cell death. The final outcome depends on external factors such as the nature of the stress and its intensity. It also largely depends on the capacity of the cell itself to cope with the stress. Different types of response are additionnaly interconnected : while the early response to a stress may involve activation of defense and repair mechanisms, failure to recover homeostasis can subsequently lead to cell death.

Cell death in response to various detrimental stimuli will often involve the execution of a tightly regulated program named apoptosis (type I programmed cell death). This suicide process ensures the elimination of damaged and potentially "dangerous" cells. For instance, failure to undergo apoptosis in response to DNA damage may promote the propagation of mutations and hence favor tumorigenesis. Of note, cancer cells develop various strategies to avoid cell death by apoptosis.

The work of our team focuses on two themes: (A) the study of programmed cell deaths, with a special interest of the mechanisms of p53-dependent apoptosis; (2) the deciphering of the mechanisms of action of natural or synthetic molecules showing promising anti-cancer activities.

  1. The gene encoding for p53 is the most frequently mutated gene in human cancer, with an overall mutation rate over 50%. The tumor suppressor p53, also named the guardian of the genome, plays a central role in the apoptotic process. Our aim is to decipher how activation of P53 promotes cell death. A better understanding of these mechanisms will allow defining new therapeutic strategies to combat cancer cells, based on the reactivation of p53-dependent pathways.
     
  2. Cancer chemotherapy involves the use of drugs to interfere with cancer development. Recently, we study in the lab the natural polyphenol resveratrol (found for instance in blueberries, grapes and red wine). We found that resveratrol induces extensive DNA damage in colon cancer cells, resulting in cell death by apoptosis. Current projects aim to developm novel resveratrol derivatives with an improved ability to trigger apoptosis.