Prof. Johanna Myllyharju

Maintenance of oxygen and extracellular matrix (ECM) homeostases is crucial for normal development and physiology, and several pathologies are associated with hypoxia or ECM abnormalities. We focus on the central enzymes regulating these two fundamental biological processes: 1) the prolyl 4-hydroxylases that control the hypoxia response pathway via determination of the oxygen-dependent fate of the hypoxia-inducible transcription factor HIF, and 2) the key enzymes of collagen synthesis, the collagen prolyl 4-hydroxylases, lysyl hydroxylases and lysyl oxidase. To understand the functions of these enzymes, their roles in development and various pathological conditions, and their potential as therapeutic targets, we are utilizing a wide repertoire of methods ranging from analysis of the catalytic and inhibitory properties of the recombinant enzymes to cell biology and animal models. Interestingly, the key enzymes of collagen synthesis are HIF targets and thus regulation of ECM homeostasis and the hypoxia response are closely linked. Detailed information on these key regulatory enzymes will create novel opportunities for pharmacological intervention in pathological conditions such as anemia, ischemia, inflammation, cancer and fibrosis. We have a longterm collaboration with FibroGen Inc. in our preclinical studies.