Systems Medicine

Group Leader

Matej Orešič, Ph.D., Adj. Prof.
matej.oresic@utu.fi

Contact Information

Matej Orešič
Turku Centre for Biotechnology
P.O. Box 123, BioCity
(Street addr. Tykistökatu 6 B)
FIN-20521 Turku, Finland
Phone: +358 44 972 6094
Email: matej.oresic@utu.fi
(LinkedIn) (Twitter)(Orcid)
(Google Scholar) (ResearchGate) (Loop)
Profile at SyMMyS CoE WWW site
Curriculum Vitae
Publications

Personel

Alex Dickens, D.Phil. – Postdoctoral researcher
Esko Kemppainen, Ph.D. – Postdoctoral researcher
Santosh Lamichhane, Ph.D. – Postdoctoral researcher
Mari Päiviö, Ph.D. – Postdoctoral researcher
Krista Rantanen, Ph.D. – Project manager
Tuukka Rönkkö, M.Sc. – Project researcher
Partho Sen, Ph.D. – Postdoctoral researcher
Tuulia Hyötyläinen, Ph.D., Prof. (Örebro University) – Affiliated member

Description of the Research

Our main research area is systems medicine, particularly metabolomics applications in biomedical research and related integrative bioinformatics. Specifically, we am particularly interested in the identification of disease vulnerabilities associated with different metabolic phenotypes and the underlying mechanisms linking these vulnerabilities with the development of specific disorders or their co-morbidities. Such in depth understanding of the metabolic phenotypes in health and disease is crucial if one is to implement personalized medicine. Dr. Orešič initiated the popular MZmine open source project, leading to popular software for metabolomics data processing.

Main Ongoing Research Projects

  • Strategic Research Agreement, Juvenile Diabetes Research Foundation (9/2016-9/2018): Metabolomic and Proteomic markers staging progression to type 1 diabetes in autoantibody positive children – PI
  • Strategic Research Agreement, Juvenile Diabetes Research Foundation (9/2016-9/2018): Mother-infant interactions in relation to potential biomarkers of beta-cell autoimmunity and type 1 diabetes – PI
  • Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research (2012-2017) – PI
  • Strategic Research Agreement, Juvenile Diabetes Research Foundation (Integrative multi-omic study of early progression to type 1 diabetes; 2014-2017) – PI
  • pHealth Programme, multi-PI collaborative project, Academy of Finland (Personalised medicine to predict and prevent Type 1 Diabetes; 9/2015-8/2019) – Co-PI
  • EU H2020 EPoS (Elucidating Pathways of Steatohepatitis) – Workpackage leader
  • EU FP7 METSY (Integrated neuroimaging and metabolic platform for characterisation of early psychosis and prediction of patient outcomes) – Coordinator

Honors and awards

Lifetime Honorary Fellow award to M. Orešič (2016, Metabolomics Society), in recognition of his groundbreaking development of metabolomics data processing tools and powerful analytical methods that have enabled systems-level investigations of processes that lead to obesity and diabetes, with a specific focus on type 1 diabetes.

Selected Publications

Suvitaival T, Bondia-Pons I, Yetukuri L, Pöhö P, Nolan JJ, Hyötyläinen T, Kuusisto J, Orešič M. Lipidome as a predictive tool in progression to type 2 diabetes in Finnish men. Metabolism. 2017. doi: 10.1016/j.metabol.2017.08.014

Suvitaival T, Mantere O, Kieseppä T, Mattila I, Pöhö P, Hyötyläinen T, Suvisaari J, Orešič M. Serum metabolite profile associates with the development of metabolic co-morbidities in first-episode psychosis. Transl Psychiatry. 2016 Nov 15;6(11):e951. doi: 10.1038/tp.2016.222

Orešič M, Posti JP, Kamstrup-Nielsen MH, Takala RS, Lingsma HF, Mattila I, Jäntti S, Katila AJ, Carpenter KL, Ala-Seppälä H, Kyllönen A, Maanpää HR, Tallus  J, Coles JP, Heino I, Frantzén J, Hutchinson PJ, Menon DK, Tenovuo O, Hyötyläinen T. Human Serum Metabolites Associate With Severity and Patient Outcomes in Traumatic Brain Injury. EBioMedicine. 2016 Jul 15. doi: 10.1016/j.ebiom.2016.07.015

Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA, Forslund K, Hildebrand F, Prifti E, Falony G, Le Chatelier E, Levenez F, Doré J, Mattila I, Plichta DR, Pöhö P, Hellgren LI, Arumugam M, Sunagawa S, Vieira-Silva S, Jørgensen T, Holm JB, Trošt K, Consortium M, Kristiansen K, Brix S, Raes J, Wang J, Hansen T, Bork P, Brunak S, Oresic M, Ehrlich SD, Pedersen O. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 2016; 535:376-81.

Hyötyläinen T, Jerby L, Petäjä EM, Mattila I, Jäntti S, Auvinen P, Gastaldelli A, Yki-Järvinen H, Ruppin E, Orešič M.Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease. Nat Commun. 2016 Feb 3;7:8994. doi: 10.1038/ncomms9994

Luukkonen PK, Zhou Y, Sädevirta S, Leivonen M, Arola J, Orešič M, Hyötyläinen T, Yki-Järvinen H. Hepatic ceramides dissociate steatosis and insulin resistance in patients with non-alcoholic fatty liver disease. J Hepatol. 2016; 64(5):1167-75

A. D. Kostic, D. Gevers, H. Siljander, T. Vatanen, T. Hyötyläinen, A.-M. Hämäläinen, A. Peet, V. Tillmann, P. Pöho, I. Mattila, H. Lähdesmäki, E. A. Franzosa, O. Vaarala, M. de Goffau, H. Harmsen, J. Ilonen, S. M. Virtanen, C. B. Clish, M. Orešič, C. Huttenhower, M. Knip, R. J. Xavier. The Dynamics of the Human Infant Gut Microbiome in Development and in Progression towards Type 1 Diabetes. Cell Host Microbe 17(2): 260-273 (2015).

B. Jørgenrud, S. Jäntti, I. Mattila, P. Pöhö, K. S. Rønningen, H. Yki-Järvinen, M. Orešič, T. Hyötyläinen. The influence of sample collection methodology and sample preprocessing on the blood metabolic profile. Bioanalysis 7(8): 991-1006 (2015).

T. U. Greiner, T. Hyötyläinen, M. Knip, F. Bäckhed, M. Orešič. The gut microbiota modulates glycaemic control and serum metabolite profile in Non-Obese Diabetic mice. PLoS ONE 9(11): e110359 (2014).

S. E. Jäntti, M. Kivilompolo, L. Öhrnberg, K. H. Pietiläinen, H. Nygren, M. Orešič, T. Hyötyläinen. Quantitative profiling of bile acids in blood, adipose tissue, intestine, and gall bladder samples using ultra high performance liquid chromatography-tandem mass spectrometry. Anal. Bioanal. Chem. 406: 7799-7815 (2014).

Hyötyläinen T, Orešič M. Systems biology strategies to study lipidomes in health and disease. Prog Lipid Res. 55:43-60 (2014).

Bondia-Pons I, Maukonen J, Mattila I, Rissanen A, Saarela M, Kaprio J, Hakkarainen A, Lundbom J, Lundbom N, Hyötyläinen T, Pietiläinen KH, Orešič M. Metabolome and fecal microbiota in monozygotic twin pairs discordant for weight: a Big Mac challenge. FASEB J. 28:4169-79 (2014).

D. La Torre, T. Seppänen-Laakso, H. E. Larsson, T. Hyötyläinen, S. A. Ivarsson, Å. Lernmark, M. Orešič, the DiPiS study group, Decreased cord-blood phospholipids in young age at onset type 1 diabetes. Diabetes 62: 3951-3956 (2013).

M. Orešič, T. Hyötyläinen, A. Kotronen, P. Gopalacharyulu, H. Nygren, J. Arola, S. Castillo, I. Mattila, A. Hakkarainen, R. J.H. Borra, M.-J. Honka, A. Verrijken, S. Francque, P. Iozzo, M. Leivonen, N. Jaser, A. Juuti, T. I. A. Sørensen, P. Nuutila, L. Van Gaal, H. Yki-Järvinen, Prediction of non-alcoholic fatty liver disease and liver fat content by serum molecular lipids. Diabetologia 56: 2266-2274 (2013).

M. Orešič, P. Gopalacharyulu, J. Mykkänen, N. Lietzen, M. Mäkinen, H. Nygren, S. Simell, V. Simell, H. Hyöty, R. Veijola, J. Ilonen, M. Sysi-Aho, M. Knip, T. Hyötyläinen, O. Simell, Cord serum lipidome in prediction of islet autoimmunity and type 1 diabetes. Diabetes 62: 3268-3274 (2013). (Faculty of 1000 recommendation)

S. I. Sayin, A. Wahlström, J. Felin, S. Jäntti, H.-U. Marschall, K. Bamberg, B. Angelin, T. Hyötyläinen, M. Orešič, F. Bäckhed, Gut microbiota regulates bile acid metabolism by reducing the levels of taurobetamuricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17, 225–235 (2013).

T. Hyötyläinen, I. Mattila, S. Wiedmer, A. Koivuniemi, M.-R. Taskinen, H. Yki-Järvinen, M. Orešič, Metabolomic analysis of polar metabolites in lipoprotein fractions identifies lipoprotein-specific metabolic profiles and their association with insulin resistance. Mol. Biosyst. 8: 2559-2565 (2012).

M. Orešič, T. Seppänen-Laakso, D. Sun, J. Tang, S. Therman, R. Viehman, U. Mustonen, T. G. M. van Erp, T. Hyötyläinen, P. Thompson, A. W. Toga, M. O. Huttunen, J. Suvisaari, J. Kaprio, J. Lönnqvist, T. D. Cannon, Phospholipids and insulin resistance in psychosis: a lipidomics study of twin pairs discordant for schizophrenia. Genome Med. 4: e1 (2012).

M. Orešič, T. Hyötyläinen, S.-K. Herukka, M. Sysi-Aho, I. Mattila, T. Seppänan-Laakso, V. Julkunen, P. V. Gopalacharyulu, M. Hallikainen, J. Koikkalainen, M. Kivipelto, S. Helisalmi, J. Lötjönen, H. Soininen, Metabolome in progression to Alzheimer’s disease. Transl. Psychiatry 1: e57 (2011). (Commentary in Alzheimer Research Forum) (Commentary in Neurology Today)

M. Sysi-Aho, A. Ermolov, P. V. Gopalacharyulu, A. Tripathi, T. Seppänen-Laakso, J. Maukonen, I. Mattila, S. T. Ruohonen, L. Vähätalo, L. Yetukuri, T. Härkönen, E. Lindfors, J. Nikkilä, J. Ilonen, O. Simell, M. Saarela, M. Knip, S. Kaski, E. Savontaus, M. Orešič, Metabolic regulation in progression to autoimmune diabetes. PLoS Comp. Biol. 7 (10): e1002257 (2011).

K. Pietiläinen, T. Róg, T. Seppänen-Laakso, S. Virtue, P. Gopalacharyulu, J. Tang, S. Rodriguez-Cuenca, A. Maciejewski, J. Naukkarinen, A. Rissanen, A.-L. Ruskeepää, P. Niemelä, V. Velagapudi, S. Castillo, H. Nygren, T. Hyötyläinen, J. Kaprio, H. Yki-Järvinen, I. Vattulainen, A. Vidal-Puig, M. Orešič, Association of lipidome remodeling in the adipocyte membrane with acquired obesity in humans. PLoS Biol. 9(6): e1000623 (2011). (commentary)

M. Orešič, J. Tang, T. Seppänen-Laakso, I. Mattila, S. E. Saarni, S. I. Saarni, J. Lönnqvist, M. Sysi-Aho, T. Hyötyläinen, J. Perälä, J. Suvisaari, Metabolome in schizophrenia and other psychotic disorders: a general population-based study. Genome Med. 3: e19 (2011).

M. Hilvo, C. Denkert, L. Lehtinen, B. Müller, S. Brockmöller, T. Seppänen-Laakso, J. Budczies, E. Bucher, L. Yetukuri, S. Castillo, E. Berg, H. Nygren, M. Sysi-Aho, J. L. Griffin, O. Fiehn, S. Loibl, C. Richter-Ehrenstein, C. Radke, T. Hyötyläinen, O. Kallioniemi, K. Iljin, M. Orešič, Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression. Cancer Res. 71: 3236-3245 (2011).

T. Pluskal, S. Castillo, A. Villar-Briones, M. Orešič, MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinformatics 11: 395 (2010).

J. Westerbacka, A. Kotronen, B. A. Fielding, J. Wahren, L. Hodson, J. Perttilä, T. Seppänen-Laakso, T. Suortti, J. Arola, R. Hultcrantz, S. Castillo, V. M. Olkkonen, K. N. Frayn, M. Orešič, H. Yki-Järvinen, Splanchnic balance of free fatty acids, endocannabinoids and lipids in subjects with NAFLD. Gastroenterology 139: 1961-1971 (2010).

L. Yetukuri, S. Söderlund, A. Koivuniemi, T. Seppänen-Laakso, P. S. Niemelä, M. Hyvönen, M.-R. Taskinen, I. Vattulainen, M. Jauhiainen, M. Orešič. Composition and lipid spatial distribution of High Density Lipoprotein particles in subjects with low and high HDL-cholesterol, J. Lipid Res. 51: 2341-2351 (2010).

V. R. Velagapudi, R. Hezaveh, C. S. Reigstad, P. V. Gopalacharyulu, L. Yetukuri, S. Islam, J. Felin, R. Perkins, J. Borén, M. Orešič, and Fredrik Backhed, The gut microbiota modulates host energy and lipid metabolism in mice. J. Lipid Res. 51: 1101-1112 (2010).

M. Orešič, T. Seppänen-Laakso, L. Yetukuri, F. Bäckhed, V. Hänninen, Gut microbiota affects lens and retinal lipid composition, Exp. Eye Res. 89, 604-607 (2009).

A. Kotronen, V. R. Velagapudi, L. Yetukuri, J. Westerbacka, R. Bergholm, K. Ekroos, J. Makkonen, M.-R. Taskinen, M. Orešič, H. Yki-Järvinen, Saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations, Diabetologia 52(4), 684-690 (2009).

P. V. Gopalacharyulu, V. R. Velagapudi, E. Lindfors, Eran Halperin, M. Orešič, Dynamic network topology changes in functional modules predict responses to oxidative stress in yeast, Mol. BioSyst. 5, 276-287 (2009).

M. Orešič, S. Simell, M. Sysi-Aho, K. Näntö-Salonen, T. Seppänen-Laakso, V. Parikka, M. Katajamaa, A. Hekkala, I. Mattila, P. Keskinen, L. Yetukuri, A. Reinikainen, J. Lähde, T. Suortti, J. Hakalax, T. Simell, H. Hyöty, R. Veijola, J. Ilonen, R. Lahesmaa, M. Knip, O. Simell, Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes, J. Exp. Med. 205(13), 2975-2984 (2008). (commentary) (Faculty of 1000 Biology evaluation)

J. Nikkilä, M. Sysi-Aho, A. Ermolov, T. Seppänen-Laakso, O. Simell, S. Kaski, M. Orešič, Gender dependent progression of systemic metabolic states in early childhood, Mol. Syst. Biol. 4, e197 (2008).

M. Katajamaa and M. Orešič, Processing methods for differential analysis of LC/MS profile data, BMC Bioinformatics 6:179 (2005).

M. Orešič and D. Shalloway, Specific Correlations between Relative Synonymous Codon Usage and Protein Secondary Structure, J. Mol. Biol. 281, 31-48 (1998).

M. Orešič and D. Shalloway, Hierarchical characterization of energy landscapes using Gaussian packet states, J. Chem. Phys. 101, 9844-9856 (1994).