Molecular and Functional Genetics 

 

Mikko Hiltunen
Research Director, Docent
Finnish Academy Research Fellow

University of Eastern Finland
Institute of Clinical Medicine / Neurology
P.O.Box 1627 (Yliopistonranta 1C)
FI-70211 Kuopio
Finland

+358-(0)40-355 2014
+358-(0)40-355 2694 (lab)
mikko.hiltunen( at )uef.fi
 

Academic Degrees

  • MSc (Biotechnology), University of Kuopio, 1995
  • PhD (Neuroscience), University of Kuopio, 2001
  • Docent (Molecular genetics), University of Kuopio, 2005

Major Positions and Appointments

  • Researcher (Molecular biology): National Veterinary and Food Research Institute, Kuopio Regional Laboratory, Finland, 1995-1996
  • PhD-student (Neuroscience/molecular genetics): Department of Neuroscience and Neurology, Kuopio University, Finland, 1996-2001
  • Project Manager: Department of Neuroscience and Neurology/Mediteknia, Kuopio University, Finland, 2001-2003
  • Research Doctor of Finnish Academy: Department of Neuroscience and Neurology, Kuopio University/Mediteknia, Finland; Genetics and Aging Research Unit, Center for Aging, Genetics, and Neurodegeneration, Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, USA, 2002-2004
  • Research Fellow: Genetics and Aging Research Unit, Center for Aging, Genetics, and Neurodegeneration, Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, USA, 2003-2006 

Selected Publications

Cysteine 27 variant of the delta-opioid receptor affects amyloid precursor protein processing through altered endocytic trafficking. Sarajärvi T, Tuusa JT, Haapasalo A, Lackman JJ, Sormunen R, Helisalmi S, Roehr JT, Parrado AR, Mäkinen P, Bertram L, Soininen H, Tanzi RE, Petäjä-Repo UE, Hiltunen M. Mol Cell Biol. 2011 Jun;31(11):2326-40.

Contribution of genetic and dietary insulin  resistance to Alzheimer phenotype in APP/PS1 transgenic mice. Hiltunen M, Khandelwal VK, Yaluri N, Tiilikainen T, Tusa M, Koivisto H, Krzisch M, Vepsäläinen S, Mäkinen P, Kemppainen S, Miettinen P, Haapasalo A, Soininen H, Laakso M, Tanila H. J Cell Mol Med. 2011, In press.

Alzheimer's Disease-Associated Ubiquilin-1 Regulates Presenilin-1 Accumulation and Aggresome Formation. Viswanathan J, Haapasalo A, Böttcher C, Miettinen R, Kurkinen KM, Lu A, Thomas A, Maynard CJ, Romano D, Hyman BT, Berezovska O, Bertram L, Soininen H, Dantuma NP, Tanzi RE, Hiltunen M. Traffic. 2011 Mar;12(3):330-48.

 APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Genin E, Hannequin D, Wallon D, Sleegers K, Hiltunen M, Combarros O, Bullido MJ, Engelborghs S, De Deyn P, Berr C, Pasquier F, Dubois B, Tognoni G, Fiévet N, Brouwers N, Bettens K, Arosio B, Coto E, Del Zompo M, Mateo I, Epelbaum J, Frank-Garcia A, Helisalmi S, Porcellini E, Pilotto A, Forti P, Ferri R, Scarpini E, Siciliano G, Solfrizzi V, Sorbi S, Spalletta G, Valdivieso F, Vepsäläinen S, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossù P, Hanon O, Piccardi P, Annoni G, Seripa D, Galimberti D, Licastro F, Soininen H, Dartigues JF, Kamboh MI, Van Broeckhoven C, Lambert JC, Amouyel P, Campion D. Mol Psychiatry. 2011 Sep;16(9):903-7.

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM, Abraham R, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Jones N, Stretton A, Thomas C, Richards A, Ivanov D, Widdowson C, Chapman J, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Beaumont H, Warden D, Wilcock G, Love S, Kehoe PG, Hooper NM, Vardy ER, Hardy J, Mead S, Fox NC, Rossor M, Collinge J, Maier W, Jessen F, Rüther E, Schürmann B, Heun R, Kölsch H, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Frölich L, Hampel H, Gallacher J, Hüll M, Rujescu D, Giegling I, Goate AM, Kauwe JS, Cruchaga C, Nowotny P, Morris JC, Mayo K, Sleegers K, Bettens K,Engelborghs S, De Deyn PP, Van Broeckhoven C, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Tsolaki M, Singleton AB, Guerreiro R, Mühleisen TW, Nöthen MM, Moebus S, Jöckel KH, Klopp N, Wichmann HE, Pankratz VS, Sando SB, Aasly JO, Barcikowska M, Wszolek ZK, Dickson DW, Graff-Radford NR, Petersen RC; Alzheimer's Disease Neuroimaging Initiative, van Duijn CM, Breteler MM, Ikram MA, DeStefano AL, Fitzpatrick AL, Lopez O, Launer LJ, Seshadri S; CHARGE consortium, Berr C, Campion D, Epelbaum J, Dartigues JF, Tzourio C, Alpérovitch A, Lathrop M; EADI1 consortium, Feulner TM, Friedrich P, Riehle C, Krawczak M, Schreiber S, Mayhaus M, Nicolhaus S, Wagenpfeil S, Steinberg S, Stefansson H, Stefansson K, Snaedal J, Björnsson S, Jonsson PV, Chouraki V, Genier-Boley B, Hiltunen M, Soininen H, Combarros O, Zelenika D, Delepine M, Bullido MJ, Pasquier F, Mateo I, Frank-Garcia A, Porcellini E, Hanon O, Coto E, Alvarez V, Bosco P, Siciliano G, Mancuso M, Panza F, Solfrizzi V, Nacmias B, Sorbi S, Bossù P, Piccardi P, Arosio B, Annoni G, Seripa D, Pilotto A, Scarpini E, Galimberti D, Brice A, Hannequin D, Licastro F, Jones L, Holmans PA, Jonsson T, Riemenschneider M, Morgan K, Younkin SG, Owen MJ, O'Donovan M, Amouyel P, Williams J. Nat Genet. 2011 May;43(5):429-35.

Down-regulation of seladin-1 increases BACE1 levels and activity through enhanced GGA3 depletion during apoptosis. Sarajärvi T, Haapasalo A, Viswanathan J, Mäkinen P, Laitinen M, Soininen H, Hiltunen M. J Biol Chem. 2009 Dec 4;284(49):34433-43.

Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Jean-Charles Lambert, Simon Heath, Gael Even, Dominique Campion, Kristel Sleegers, Mikko Hiltunen, Onofre Combarros, Diana Zelenika, Maria J Bullido, Béatrice Tavernier, Luc Letenneur, Karolien Bettens, Claudine Berr, Florence Pasquier, Nathalie Fiévet, Pascale Barberger-Gateau, Sebastiaan Engelborghs, Peter De Deyn, Ignacio Mateo, Ana Franck, Seppo Helisalmi, Elisa Porcellini, Olivier Hanon, the European Alzheimer's Disease Initiative Investigators, Marian M de Pancorbo, Corinne Lendon, Carole Dufouil, Céline Jaillard, Thierry Leveillard, Victoria Alvarez, Paolo Bosco, Michelangelo Mancuso, Francesco Panza, Benedetta Nacmias, Paola Bossù, Paola Piccardi, Giorgio Annoni, Davide Seripa, Daniela Galimberti, Didier Hannequin, Federico Licastro, Hilkka Soininen, Karen Ritchie, Hélène Blanché, Jean-François Dartigues, Christophe Tzourio, Ivo Gut, Christine Van Broeckhoven, Annick Alpérovitch, Mark Lathrop & Philippe Amouyel. Nature Genetics, 6 September 2009 | doi:10.1038/ng.439.

Focal cerebral ischemia in rats alters APP processing and expression of Abeta peptide degrading enzymes in the thalamus. Hiltunen M, Mäkinen P, Peräniemi S, Sivenius J, van Groen T, Soininen H, Jolkkonen J. Neurobiol Dis. 2009 Jul;35(1):103-13.

An association study between granulin gene polymorphisms and Alzheimer's disease in Finnish population. Viswanathan J, Mäkinen P, Helisalmi S, Haapasalo A, Soininen H, Hiltunen M. Am J Med Genet B Neuropsychiatr Genet. 2009 Jul 5;150B(5):747-50.

“No Association between CALHM1 and Alzheimer’s Disease Risk”. Bertram L, Schjeide BMM, Holi B, Mullin K, Hiltunen M, Soininen H, Ingelsson M, Lannfelt L, Blacker D, Tanzi RE. Cell. 2008 Dec 12;135(6):993-4.

Genetic study evaluating LDLR polymorphisms and Alzheimer's disease. Lamsa R, Helisalmi S, Herukka SK, Tapiola T, Pirttila T, Vepsalainen S, Hiltunen M, Soininen H. Neurobiol Aging. 2008 Jun;29(6):848-55.

Depletion of GGA3 Stabilizes BACE and Enhances beta-Secretase Activity. Tesco G, Koh YH, Kang EL, Cameron AN, Das S, Sena-Esteves M, Hiltunen M, Yang SH, Zhong Z, Shen Y, Simpkins JW, Tanzi RE. Neuron. 2007 Jun 7;54(5):721-37.

Insulin degrading enzyme is genetically associated with Alzheimer's disease in the Finnish population. Vepsalainen S, Parkinson M, Helisalmi S, Mannermaa A, Soininen H, Tanzi R, Bertram L, Hiltunen M. J Med Genet. 2007, 44(9):606-82.

Ubiquilin 1 modulates amyloid precursor protein trafficking and Abeta secretion. Hiltunen M, Lu A, Thomas AV, Romano DM, Kim M, Jones PB, Xie Z, Kounnas MZ, Wagner SL, Berezovska O, Hyman BT, Tesco G, Bertram L, Tanzi RE. J Biol Chem. 2006 Oct 27;281(43):32240-53.

Interaction between presenilin 1 and ubiquilin 1 as detected by fluorescence lifetime imaging microscopy and a high-throughput fluorescent plate reader. Thomas AV, Herl L, Spoelgen R, Hiltunen M, Jones PB, Tanzi RE, Hyman BT, Berezovska O. J Biol Chem. 2006 Sep 8;281(36):26400-7.

APP substitutions V715F and L720P alter PS1 conformation and differentially affect Abeta and AICD generation. Tesco G, Ginestroni A, Hiltunen M, Kim M, Dolios G, Hyman BT, Wang R, Berezovska O, Tanzi RE.  J Neurochem. 2005 Oct;95(2):446-56.

Family-based association between Alzheimer's disease and variants in UBQLN1. Bertram L, Hiltunen M, Parkinson M, Ingelsson M, Lange C, Ramasamy K, Mullin K, Menon R, Sampson AJ, Hsiao MY, Elliott KJ, Velicelebi G, Moscarillo T, Hyman BT, Wagner SL, Becker KD, Blacker D, Tanzi RE. N Engl J Med. 2005 Mar 3;352(9):884-94.

Polymorphisms in the CYP19 gene confer increased risk for Alzheimer disease. Iivonen S, Corder E, Lehtovirta M, Helisalmi S, Mannermaa A, Vepsalainen S, Hanninen T, Soininen H, Hiltunen M. Neurology. 2004 Apr 13;62(7):1170-6.

Seladin-1 transcription is linked to neuronal degeneration in Alzheimer's disease. Iivonen S, Hiltunen M, Alafuzoff I, Mannermaa A, Kerokoski P, Puoliväli J, Salminen A, Helisalmi S, Soininen H. Neuroscience 2002 113: 301-310.

Genome-wide linkage disequilibrium mapping of late-onset Alzheimer's disease in Finland. Neurology. Hiltunen M, Mannermaa A, Thompson D, Easton D, Pirskanen M, Helisalmi S, Koivisto AM, Lehtovirta M, Ryynanen M, Soininen H. 2001 Nov 13;57(9):1663-8.

Identification of a novel 4.6-kb genomic deletion in presenilin-1 gene which results in exclusion of exon 9 in a Finnish early onset Alzheimer's disease family: an Alu core sequence-stimulated recombination? Hiltunen M, Helisalmi S, Mannermaa A, Alafuzoff I, Koivisto AM, Lehtovirta M, Pirskanen M, Sulkava R, Verkkoniemi A, Soininen H. Eur J Hum Genet. 2000 Apr;8(4):259-66.

MPO and APOE-ε4 polymorphisms interact to increase risk for AD in Finnish males. Reynolds W F, Hiltunen M, Pirskanen M, Mannermaa A, Helisalmi S, Lehtovirta M, Alafuzoff I, Soininen H. Neurology 2000 55: 1284-1290.

Linkage disequilibrium in the 13q12 region in Finnish late onset Alzheimer's disease patients. Hiltunen M, Mannermaa A, Koivisto A M, Lehtovirta M, Helisalmi S, Ryynänen M, Riekkinen P S, Soininen H. Eur J Hum Genet 1999 7: 652-658.