Research Objective Group Professor Fandrey
Hypoxia and inflammation
Hypoxia is a hallmark of inflammation (due to edema and occlusion of vessels and increased oxygen consumption by infiltrating immune cells). To investigate the link between hypoxia-inducible factors (HIFs) and inflammatory processes, we study inflammatory responses in mice with a HIF-α knockout in cells of e.g. the myeloid cell lineage in in vivo and in vitro models. Isolated bone-marrow derived immune cells and epithelial cells with or without a HIF-α knockout are used for in vitro experiments analyzing stimulated cytokine expression, epithelial integrity and survival under normoxic and hypoxic conditions.
Hypoxia inducible factor-1α and p53 in transition from ulcerative colitis to colorectal cancer
Our study focuses on the role of hypoxia inducible factor-1α (HIF-1α) and its interaction with p53 (frequently mutated in colorectal diseases). Loss of HIF-1α in some cells seems to protect against the transition from ulcerative colitis to colorectal cancer, whereas the loss of p53 appears to promote the growth of cancer. We want to analyze which of the two processes is the dominant one and want to understand the molecular relation between HIF-1α (and the other isoforms) and p53.
Role of the Hypoxia-inducible Factor 2 in brain injury and recovery
HIF-2 represents a tissue-specific isoform of the hypoxia-inducible factors to regulate the cellular adaptation to hypoxia. In acute cases of oxygen deficiency, HIF transcription factors ensure the timely restoration of adequate oxygen supply or metabolic adaptation. Especially in stroke, which has a high mortality and often a poor prognosis due to the ischemic insult, restoration of oxygen supply is of vital importance. Unfortunately, these endogenous mechanisms are not sufficient to protect the brain tissue. For this reason, we study the endogenous reactions to a sudden hypoxic insult in detail and ideally use the findings to develop new therapeutic approaches for stroke patients.
Cross-talk of thyroid hormones and hypoxia-inducible factors in the retina
Our main aim is to understand the cross-talk of thyroid hormones and hypoxia-inducible factors (HIFs) in the retina. The retina is a target for thyroid hormones and has the highest cell-specific oxygen consumption; it is prone to an imbalance of demand to supply of oxygen. We study involvement of HIFs in the pathophysiology of retinal degenerative diseases such as age-related macular degeneration (AMD), a leading cause for blindness in elderly people.
Protein-protein interaction of hypoxia-inducible factors (HIFs)
HIFs form transcriptionally active complexes with co-activators. We use advanced microscopic techniques as FRET (Fluorescence Resonance Energy Transfer) and FLIM (Fluorescence Lifetime Microscopy at the IMCES) to investigate protein-protein interactions of HIF subunits and HIF inhibitors and to analyze oxygen sensing in living cells.