A post-doctoral position and a PhD student position are open in the laboratory of Prof. Peppi Karppinen (Koivunen) in a project “Hypoxia-response pathway as a target for novel therapeutics” at the Faculty of Biochemistry and Molecular Medicine, University of Oulu.

Hypoxia-inducible factor (HIF) is the key regulator of oxygen homeostasis. It initiates the rescue response of cells and tissues to oxygen deprivation that includes e.g. upregulation of erythropoietin, VEGF and genes for glucose metabolism. Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) are enzymes that sense oxygen levels and regulate HIF abundance accordingly. We have shown that regulation of HIF stability via genetic or pharmacologic inhibition of HIF-P4Hs can protect from cardiac ischemic insults and surprisingly protect from obesity and metabolic syndrome. We have also shown that some cancer-associated oncometabolites function via HIF. Several lines of research stemming from our recent results are ongoing in the laboratory and the exact project will be agreed on with the successful candidates.

We use a wide selection of experimental mouse models, biochemistry and molecular biology. Experience from in vivo work with mice is necessary as well as knowledge and keen interest in the methods. Successful candidates are highly-motivated, co-operative and have good skills in oral and written English. For the post-doctoral position a successful thesis project with good publications is expected. Applications should be sent to peppi.karppinen@oulu.fimailto:peppi.karppinen@oulu.fi no later than 30 November 2014.

Recent publications from the project:

1: Lorenzo FR, Huff C, Myllymäki M, Olenchock B, Swierczek S, Tashi T, Gordeuk V, Wuren T, Ri-Li G, McClain DA, Khan TM, Koul PA, Guchhait P, Salama ME, Xing J, Semenza GL, Liberzon E, Wilson A, Simonson TS, Jorde LB, Kaelin WG Jr, Koivunen P, Prchal JT. A genetic mechanism for Tibetan high-altitude adaptation. Nat Genet. 2014;46:951-6. 2: Rahtu-Korpela L, Karsikas S, Hörkkö S, Blanco Sequeiros R, Lammentausta E, Mäkelä KA, Herzig KH, Walkinshaw G, Kivirikko KI, Myllyharju J, Serpi R, Koivunen P. HIF Prolyl 4-Hydroxylase-2 Inhibition Improves Glucose and Lipid Metabolism and Protects Against Obesity and Metabolic Dysfunction. Diabetes. 2014;63:3324-33. 3: Kerkelä R, Karsikas S, Szabo Z, Serpi R, Magga J, Gao E, Alitalo K, Anisimov A, Sormunen R, Pietilä I, Vainio L, Koch WJ, Kivirikko KI, Myllyharju J, Koivunen P. Activation of hypoxia response in endothelial cells contributes to ischemic cardioprotection. Mol Cell Biol. 2013;33:3321-9. 4: Palomäki S, Pietilä M, Laitinen S, Pesälä J, Sormunen R, Lehenkari P, Koivunen P. HIF-1α is upregulated in human mesenchymal stem cells. Stem Cells. 2013;31:1902-9. 5: Losman JA, Looper RE, Koivunen P, Lee S, Schneider RK, McMahon C, Cowley GS, Root DE, Ebert BL, Kaelin WG Jr. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science. 2013;339:1621-5. 6: Laitala A, Aro E, Walkinshaw G, Mäki JM, Rossi M, Heikkilä M, Savolainen ER, Arend M, Kivirikko KI, Koivunen P, Myllyharju J. Transmembrane prolyl 4-hydroxylase is a fourth prolyl 4-hydroxylase regulating EPO production and erythropoiesis. Blood. 2012;120:3336-44. 7: Koivunen P, Lee S, Duncan CG, Lopez G, Lu G, Ramkissoon S, Losman JA, Joensuu P, Bergmann U, Gross S, Travins J, Weiss S, Looper R, Ligon KL, Verhaak RG, Yan H, Kaelin WG Jr. Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature. 2012;483:484-8.

More information can be found on our website: www.oulu.fi/fbmm/peppi_karppinenhttp://www.oulu.fi/fbmm/peppi_karppinen