David Hoogewijs
Professor
PER 09 - 2.107
+41 26 300 9410
E-mail
Integrative oxygen physiology
General aims:
Our research is centered on studying novel oxygen-binding proteins as well as investigating the molecular mechanism of cellular response to reduced oxygen supply (hypoxia) using a broad variety of in vitro and in vivo molecular and cell biological techniques complemented by bioinformatical approaches.
We aim to elucidate the (patho)physiological role of particularly androglobin and cytoglobin, two recently identified mammalian globins from the post-genomic era (Keppner et al. 2020). Androglobin represents the latest addition to the globin family and consists of a calcium-dependent protease domain fused to a central circularly permuted globin domain (Hoogewijs et al 2012). While androglobin expression is restricted to postmeiotic stages of spermatogenesis (Keppner et al. 2022) it seems to be expressed as well in ciliated cells across various tissues (Koay et al. 2021). Cytoglobin on the other hand is abundantly expressed in fibroblasts from a broad range of organs as well as in renal podocytes (Randi et al. 2020) and melanoma (De Backer, De Backer et al. 2022a and De Backer et al. 2022b).
An additional research line aims to understand the differential regulation between the transcription factors hypoxia-inducible factor 1 (HIF-1) and HIF-2 in response to hypoxia with a strong focus on distal regulatory DNA regions and oxygen-dependent erythropoietin gene expression (Storti et al. 2014; Schörg et al. 2015). Apart from physiological and pathophysiological processes, including embryonic development, high-altitude adaptation, wound healing and inflammation, the mechanisms of cellular adaptation to hypoxia are of crucial importance for clinically relevant diseases such as anemia, infarction, stroke and cancer.
Given the major significance of the HIF pathway in health and disease, we aim to broaden our understanding of this elegantly sophisticated signalling system, specifically by functionally investigating novel mutations in multiple genes of the HIF system associated with secondary erythrocytosis, a rare haematological disease characterized by excessive production of red blood cells (Lenglet et al. 2018; Karaghiannis, Maric et al. 2023; Delamare et al. 2023).
