Lorenz Poellinger, MD, PhD, Professor
Oxygen deficiency (hypoxia) arises when oxygen demand exceeds supply, Hypoxia is an early pathophysiological signature in e.g. coronary heart disease, stroke, peripheral vascular disease in patients with type 2 diabetes, and in growing solid tumors in cancer disease.
Understanding the cellular and systemic responses to hypoxia is thus fundamental for human health. Mammalian cells adapt to hypoxic/ischemic conditions through a gene regulatory response pathway mediated by hypoxia-inducible factors (HIFs). This response is initiated to ensure adequate oxygen availability and at the same time minimize the influence of oxygen free radicals. Our laboratory and others have elucidated the mechanisms by which changes in O2 concentration are transduced to changes in gene expression mediated by HIF complexes. We are currently interested in understanding the epigenetic landscape in hypoxic cells, epigenetic regulatory mechanisms determining the cellular response to hypoxia, and to understand the interplay between these mechanisms and the function of hypoxia-inducible transcription factors (HIFs) in normal physiology and disease. We are also interested in targeting the cellular hypoxia response rpogram to develop new therapies in e.g. cancer disease.
- Shoichi Fumoto, Postdoctoral Researcher
- Katarina Gradin, Senior Researcher
- Michael Gralla, PhD Student
- Hideaki Nakamura, Postdoctoral Researcher
- Sandra Lücke, Postdoctoral Researcher
- Nikola Vojnovic, Project Student
The aspariginyl hydroxylase FIH (Factor Inhibiting HIF) is an essential regulator of metabolism.
Cell Metabolism 11, 364-378.
Interaction with Factor Inhibiting HIF-1 defines a novel mode of cross-coupling between the Notch and hypoxia signaling pathways.
Proc. Natl. Acad. Sci. USA 105, 3368-3373.
Epidermal sensing of oxygen is essential for systemic hypoxic response.
Cell 133, 223-234.
Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated by time and oxygen conditions in neuroblastoma - HIF-2a promotes an aggressive neuroblastoma phenotype.
Cancer Cell 10, 413-423.
Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression.
Nature 414, 550-554.