Selected Publications

Chakraborty AA, Laukka T, Myllykoski M, Ringel AE, Booker MA, Tolstorukov MY, Meng YJ, Meier SR, Jennings RB, Creech AL, Herbert ZT, McBrayer SK, Olenchock BA, Jaffe JD, Haigis MC, Beroukhim R, Signoretti S, Koivunen P, Kaelin WG Jr. Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate. Science. 2019 Mar 15;363(6432):1217-1222. doi: 10.1126/science.aaw1026. Epub 2019 Mar 14. PMID: 30872525.

Laukka T, Myllykoski M, Looper RE, Koivunen P. Cancer-associated 2-oxoglutarate analogues modify histone methylation by inhibiting histone lysine demethylases. J Mol Biol. 2018 Sep 14;430(18 Pt B):3081-3092. doi: 10.1016/j.jmb.2018.06.048. Epub 2018 Jul 5. PMID: 29981745.

Laitakari A, Ollonen T, Kietzmann T, Walkinshaw G, Mennerich D, Izzi V, Haapasaari KM, Myllyharju J, Serpi R, Dimova EY, Koivunen P. Systemic inactivation of hypoxia-inducible factor prolyl 4-hydroxylase 2 in mice protects from alcohol-induced fatty liver disease. Redox Biol. 2019 Apr;22:101145. doi: 10.1016/j.redox.2019.101145. Epub 2019 Feb 19. PMID: 30802717; PMCID: PMC6396018.

Rahikkala E, Myllykoski M, Hinttala R, Vieira P, Nayebzadeh N, Weiss S, Plomp AS, Bittner RE, Kurki MI, Kuismin O, Lewis AM, Väisänen ML, Kokkonen H, Westermann J, Bernert G, Tuominen H, Palotie A, Aaltonen L, Yang Y, Potocki L, Moilanen J, van Koningsbruggen S, Wang X, Schmidt WM, Koivunen P, Uusimaa J. Biallelic loss-of-function P4HTM gene variants cause hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities (HIDEA syndrome). Genet Med. 2019 Oct;21(10):2355-2363. doi: 10.1038/s41436-019-0503-4. Epub 2019 Apr 3. PMID: 30940925; PMCID: PMC6774999.

Leinonen H, Koivisto H, Lipponen HR, Matilainen A, Salo AM, Dimova EY, Hämäläinen E, Stavén S, Miettinen P, Myllyharju J, Koivunen P, Tanila H. Null mutation in P4h-tm leads to decreased fear and anxiety and increased social behavior in mice. Neuropharmacology. 2019 Jul 15;153:63-72. doi: 10.1016/j.neuropharm.2019.04.023. Epub 2019 Apr 25. PMID: 31029587.

Koivunen P, Kietzmann T. Hypoxia-Inducible Factor Prolyl 4-Hydroxylases and Metabolism. Trends Mol Med. 2018 Oct 31. pii: S1471-4914(18)30190-4. doi: 10.1016/j.molmed.2018.10.004. [Epub ahead of print] Review. https://authors.elsevier.com/a/1Y7xc5Eb1BHoNG

Määttä J, Sissala N, Dimova EY, Serpi R, Moore LG, Koivunen P. Hypoxia causes reductions in birth weight by altering maternal glucose and lipid metabolism.Sci Rep. 2018 Sep 11;8(1):13583.

Laukka T, Myllykoski M, Looper RE, Koivunen P. Cancer-associated 2-oxoglutarate analogues modify histone methylation by inhibiting histone lysine demethylases. J Mol Biol. 2018 Sep 14;430(18 Pt B):3081-3092. 

Koivunen P, Serpi R, Dimova EY. Hypoxia-inducible factor prolyl 4-hydroxylase inhibition in cardiometabolic diseases. Pharmacol Res. 2016 Dec;114:265-273.

Myllymäki MN, Määttä J, Dimova EY, Izzi V, Väisänen T, Myllyharju J, Koivunen P, Serpi R. Notch Downregulation and Extramedullary Erythrocytosis in Hypoxia-Inducible Factor Prolyl 4-Hydroxylase 2-Deficient Mice. Mol Cell Biol. 2017 Jan 4;37(2). pii: e00529-16.

Leinonen H, Rossi M, Salo AM, Tiainen P, Hyvärinen J, Pitkänen M, Sormunen R, Miinalainen I, Zhang C, Soininen R, Kivirikko KI, Koskelainen A, Tanila H, Myllyharju J, Koivunen P. Lack of P4H-TM in mice results in age-related retinal and renal alterations. Hum Mol Genet. 2016 Sep 1;25(17):3810-3823.

Briggs KJ, Koivunen P, Cao S, Backus KM, Olenchock BA, Patel H, Zhang Q, Signoretti S, Gerfen GJ, Richardson AL, Witkiewicz AK, Cravatt BF, Clardy J, Kaelin WG Jr. Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine. Cell. 2016 Jun 30;166(1):126-39.

Rahtu-Korpela L, Määttä J, Dimova EY, Hörkkö S, Gylling H, Walkinshaw G, Hakkola J, Kivirikko KI, Myllyharju J, Serpi R, Koivunen P. Hypoxia-Inducible Factor Prolyl 4-Hydroxylase-2 Inhibition Protects Against Development of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2016 Apr;36(4):608-17.

Laukka T, Mariani CJ, Ihantola T, Cao JZ, Hokkanen J, Kaelin WG Jr, Godley LA, Koivunen P. Fumarate and Succinate Regulate Expression of Hypoxia-inducible Genes via TET Enzymes. J Biol Chem. 2016 Feb 19;291(8):4256-65.

Karsikas S, Myllymäki M, Heikkilä M, Sormunen R, Kivirikko KI, Myllyharju J, Serpi R, Koivunen P. HIF-P4H-2 deficiency protects against skeletal muscle ischemia-reperfusion injury. J Mol Med (Berl). 2016 Mar;94(3):301-10.

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 Sep;46(9):951-6.

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 Oct;63(10):3324-33.

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 Aug;33(16):3321-9.

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 Sep;31(9):1902-9.

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 Mar 29;339(6127):1621-5.

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 Oct 18;120(16):3336-44.

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 Feb 15;483(7390):484-8.

Hyvärinen J, Hassinen IE, Sormunen R, Mäki JM, Kivirikko KI, Koivunen P, Myllyharju J. Hearts of hypoxia-inducible factor prolyl 4-hydroxylase-2 hypomorphic mice show protection against acute ischemia-reperfusion injury. J Biol Chem. 2010 Apr 30;285(18):13646-57.

Koivunen P, Tiainen P, Hyvärinen J, Williams KE, Sormunen R, Klaus SJ, Kivirikko KI, Myllyharju J. An endoplasmic reticulum transmembrane prolyl 4-hydroxylase is induced by hypoxia and acts on hypoxia-inducible factor alpha. J Biol Chem. 2007 Oct 19;282(42):30544-52.

Koivunen P, Hirsilä M, Remes AM, Hassinen IE, Kivirikko KI, Myllyharju J. Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF. J Biol Chem. 2007 Feb 16;282(7):4524-32.

Koivunen P, Hirsilä M, Kivirikko KI, Myllyharju J. The length of peptide substrates has a marked effect on hydroxylation by the hypoxia-inducible factor prolyl 4-hydroxylases. J Biol Chem. 2006 Sep 29;281(39):28712-20.

Hirsilä M, Koivunen P, Xu L, Seeley T, Kivirikko KI, Myllyharju J. Effect of  desferrioxamine and metals on the hydroxylases in the oxygen sensing pathway. FASEB J. 2005 Aug;19(10):1308-10.

Koivunen P, Hirsilä M, Günzler V, Kivirikko KI, Myllyharju J. Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases. J Biol Chem. 2004 Mar 12;279(11):9899-904.

Hirsilä M, Koivunen P, Günzler V, Kivirikko KI, Myllyharju J. Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. J Biol Chem. 2003 Aug 15;278(33):30772-80.

Last updated: 5.2.2020