Seminar

The challenge of dealing with hypoxia

Edurne Berra, PhD

Oxygen homeostasis is vital for most organisms and hypoxia, even transient, can provoke irreversible damage. To deal with hypoxia has evolved the so-called hypoxia-signalling pathway. 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 the crosstalk with other signalling pathways as a major step towards establishing its implications for health and disease, which could open future therapeutic applications. We investigate 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 ubiquitination and the DUBs that we have identified acting as new regulators of the hypoxia cascade 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. Similarly, we have provided new insights into the design of smart systems for cancer therapeutics. This lecture will cover the most promising data of the past, current and future research lines we curry out in the lab.