p53 regulation by bacteria and its impact on tumorigenesis
We are investigating the molecular mechanisms of the host response to bacterial dysbiosis, with a focus on the tumor suppressor p53 pathway.
Increasing evidence from metagenomics study highlights the role of the microbiota composition in cancer initiation, progression and resistance to therapies. Cancers are clearly associated with bacterial dysbiosis, which could be a passenger but also a driver of the tumorigenesis process. However, little is known about how the bacteria species enriched during dysbiosis promote tumorigenesis.
We are investigating the molecular mechanisms of the host response to bacterial dysbiosis, with a focus on the tumor suppressor p53 pathway. p53 plays a central role in cell signaling and is therefore strongly regulated in response to commensal and pathogenic bacteria signaling during inflammation. Moreover, p53 encodes a transcriptional program which in turns regulates the innate and adaptive immune response. Therefore, it is not surprising that bacteria have evolved different mechanisms to target and manipulate the host p53 pathway in order to establish and keep their niche. Finally, p53 is the major barrier against cancer in humans and its role as a regulator of immune response is emerging as a key component for its tumor suppressive function. Hence, bacterial interference with the p53 pathway could have important consequences for tumorigenesis.
Our main questions
How the p53 pathway is involved in the physiological host response to bacteria, i.e. inflammation and innate immune response?
How some bacteria hijack the p53 pathway for their own benefits?
How bacteria-induced deregulation of the p53 pathway influence cancer initiation and progression?
Our ultimate goal is to find new therapeutic targets in bacteria and/or the human host to help prevent of combat cancer.
To investigate these fundamental questions at the molecular level both on the bacteria and host side, this project is a collaboration performed together with an expert in microbiology of pathogenic bacteria Ass. Prof. Marie-Stephanie Aschtgen in Prof Birgitta Henriques-Normark’s lab.