Oxygen homeostasis is vital for most organisms and hypoxia, even transient, can provoke irreversible damage. To deal with hypoxia the so-called hypoxia-signalling pathway has evolved. This pathway is essential during embryonic development and in adulthood but it is also associated with a wide range of pathological states, including, but not limited, to ischemic and neurodegenerative diseases, inflammatory and metabolic disorders, and cancer.The research in our group is aimed at deciphering the molecular basis of the hypoxia cascade and its crosstalk with other signalling pathways. We are investigating the role of post-translational modifications (PTMs) by using state-of-the-art in cellulo and in vivo approaches. We have reported the physiological relevance of PHD3-SUMO conjugates as HIF transcriptional repressors. We try to understand the role of DUBs acting as new regulators of the hypoxia cascade that we have identified through a RNAi based genetic screen. In addition, we are interested in understanding the relationship between these signalling networks and pathologies in which hypoxia is involved. Our work has shown the efficient revascularisation triggered by the silencing of PHDs, opening new possibilities for therapy in ischemia. We have also provided new insights into the design of smart systems for cancer therapeutics.We believe that a detailed understanding of the signalling pathway triggered by hypoxia is a major step towards establishing its implications in health and disease and could open future therapeutic applications.
Life & Medical Sciences
- Biosciences & Health
- Molecular basis of the hypoxia cascade and its crosstalk with other signalling pathways