Circadian rhythms (CRs) are the biological response to the periodic rotations of the Earth, and allow
fundamental adaptations of organisms to a changing environment. CRs are molecularly controlled in virtually every cell by a set of transcriptional factors that control and are influenced by, core biological processes including metabolism, immune system activation, and proliferation.
My previous studies established, for the first time, that innate immune cells regulate the circadian physiology of tissues, including the susceptibility of the lung to be metastasized (JEM., 2018). In this project, we are asking the reciprocal question to reveal if cancer cells take advantage of and subvert, CRs of the innate (immune and stroma) compartments to escape anti-tumoral defense. We aim to understand how oncogenic processes rewire the CRs of the host and to elucidate strategies that halt this subversion as a new approach to fighting cancer. Our ultimate goal is to revolutionize the way we understand cancer, as it will identify the malignant roots of circadian rhythms and their impact on host defense. This research will establish a new paradigm by revealing the mechanisms underlying pro-tumorigenic clocks and will provide robust foundations for new therapies in a set of disorders in which circadian clock (dys)functions are implicated
