The Nobel Prize in Physiology or Medicine 2019 was awarded jointly to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza "for their discoveries of how cells sense and adapt to oxygen availability."
Biocenter Oulu group leaders Profs. Peppi Koivunen and Johanna Myllyharju have currently a joint BCO project “Hypoxia Response Pathway as a Target for Novel Therapeutics” and they have on-going collaboration with Nobel Prize winner professors Kaelin and Ratcliffe, and have several joint publications with them.
Lack of activity of recombinant HIF prolyl hydroxylases (PHDs) on reported non-HIF substrates. Cockman ME, Lippl K, Tian YM, Pegg HB, Figg WD Jnr, Abboud MI, Heilig R, Fischer R, Myllyharju J, Schofield CJ, Ratcliffe PJ. Elife. 2019 Sep 10;8. pii: e46490. doi: 10.7554/eLife.46490.
Update on hypoxia-inducible factors and hydroxylases in oxygen regulatory pathways: from physiology to therapeutics. Ratcliffe P, Koivunen P, Myllyharju J, Ragoussis J, Bovée JV, Batinic-Haberle I, Vinatier C, Trichet V, Robriquet F, Oliver L, Gardie B. Hypoxia (Auckl). 2017 Mar 15;5:11-20. doi: 10.2147/HP.S127042. eCollection 2017. Review.
Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate. 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. Science. 2019 Mar 15;363(6432):1217-1222. doi: 10.1126/science.aaw1026. Epub 2019 Mar 14.
Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine. 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. Cell. 2016 Jun 30;166(1):126-39. doi: 10.1016/j.cell.2016.05.042.
Fumarate and Succinate Regulate Expression of Hypoxia-inducible Genes via TET Enzymes. Laukka T, Mariani CJ, Ihantola T, Cao JZ, Hokkanen J, Kaelin WG Jr, Godley LA, Koivunen P. J Biol Chem. 2016 Feb 19;291(8):4256-65. doi: 10.1074/jbc.M115.688762. Epub 2015 Dec 23.
A genetic mechanism for Tibetan high-altitude adaptation. 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. Nat Genet. 2014 Sep;46(9):951-6. doi: 10.1038/ng.3067. Epub 2014 Aug 17.
Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase. Zheng X, Zhai B, Koivunen P, Shin SJ, Lu G, Liu J, Geisen C, Chakraborty AA, Moslehi JJ, Smalley DM, Wei X, Chen X, Chen Z, Beres JM, Zhang J, Tsao JL, Brenner MC, Zhang Y, Fan C, DePinho RA, Paik J, Gygi SP, Kaelin WG Jr, Zhang Q. Genes Dev. 2014 Jul 1;28(13):1429-44. doi: 10.1101/gad.242131.114.
(R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Losman JA, Looper RE, Koivunen P, Lee S, Schneider RK, McMahon C, Cowley GS, Root DE, Ebert BL, Kaelin WG Jr. Science. 2013 Mar 29;339(6127):1621-5. doi: 10.1126/science.1231677. Epub 2013 Feb 7.
Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. 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. Nature. 2012 Feb 15;483(7390):484-8. doi: 10.1038/nature10898.
Last updated: 8.10.2019