David Hoogewijs
Ordentliche_r Professor_in
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). We investigate its role during postmeiotic stages of spermatogenesis (Keppner et al. 2022) and its function in ciliated cells across diverse tissues (Koay et al. 2021). Evolutionary studies demonstrate that its association with ciliated cells is deeply conserved across metazoans (Osterhof et al. 2026) while biochemical studies revealed calcium-dependent proteolytic processing of androglobin and distinctive properties of its circularly permuted globin domain (Koay et al. 2026). In parallel, we study cytoglobin as a regulator of redox homeostasis, mitochondrial metabolism and cellular stress responses. Using Cygb-deficient mice and cellular models, we demonstrated that cytoglobin protects renal podocytes against oxidative stress and that its loss impairs renal function (Randi et al. 2020). Our work in melanoma further explores how cytoglobin influences cancer cell survival and susceptibility to regulated cell death, including apoptosis, ferroptosis and pyroptosis (De Backer et al. 2022a; De Backer et al. 2022b; De Backer et al. 2024).
A complementary research line addresses the distinct regulation and functions of hypoxia-inducible factor 1 (HIF-1) and HIF-2, with particular emphasis on distal regulatory DNA regions and oxygen-dependent erythropoietin gene expression (Storti et al. 2014; Schörg et al. 2015; Idriss et al. 2026) These mechanisms of cellular adaptation to hypoxia are central to embryonic development, high-altitude adaptation, wound healing and inflammation, and contribute to diseases such as anaemia, 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 complex signalling system by functionally investigating novel mutations in multiple HIF pathway genes 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; Martin, Maric et al. 2025).
