Integrative Physiology and Pharmacology

The Integrative physiology and pharmacology research unit covers widely the field of biomedicine. The research themes cover areas such as endocrinology, metabolism, bioimaging and diagnostics, drug development and medical treatment. The methodology used includes different in vitro cell culture models and translational animal models. The most advanced microscopy, x-ray and PET devices and methods are applied on the field of bioimaging.

Research groups

Terhi Heino: Stem cells in bone and vascular biology

Terhi Heino, PhD, University Teacher, Adjunct professor of Cell Biology 

Contact: terhi.j.heino@utu.fi 

Description of Research 

Our research focuses on elucidating the role of mesenchymal stromal cells (MSC) in bone and vascular biology. We are especially interested in interactions between MSC and endothelial precursors and their potential applications in regenerative medicine. We use mainly in vitro cell cultures of human bone marrow derived primary MSCs and peripheral blood derived cells (MNC) but also use clinically relevant patient material. In summary, our research provides important novel data on cellular interactions and crucial molecular players in angiogenesis and osteogenesis. This contributes to the development of better regenerative medicine applications when aiming to enhance bone and soft tissue healing.  

Current topics 

  • Angiogenic and osteogenic potential of MSC and MNC co-cultures  
  • Functionality of myeloid angiogenic cells in vascularization  

Research group members 

  • Post-docs: MD, PhD Katriina Joensuu 
  • PhD students: MSc Liina Uusitalo-Kylmälä 
  • Other students: BSc Nandita Sabapathi 

Recent key publications  

  1. Gundestrup AK, Lynggaard CD, Forner L, Heino TJ, Jakobsen KK, Fischer-Nielsen A, Grønhøj C & von Buchwald C (2020) Mesenchymal stem cell therapy for osteoradionecrosis of the mandible: A systematic review of preclinical and human studies. Stem Cell Rev Rep. 2020 Sep 1.  
  2. Vallittu PK, Posti JP, Piitulainen JM, Serlo W, Määttä JA, Heino TJ, Pagliari S, Syrjänen SM & Forte G (2020) Biomaterial and implant induced ossification: in vitro and in vivo findings. J Tissue Eng Regen Med. 14(8):1157-1168.  
  3. Heino TJ & Määttä J (2018) Bone Marrow Niche: Role of Different Cells in Bone Metastasis. Current Molecular Biology Reports 4:80–87.  
  4. Joensuu K, Uusitalo L, Hentunen TA, Heino TJ (2018) Angiogenic potential of human mesenchymal stromal cell and circulating mononuclear cell co-cultures is reflected in the expression profiles of proangiogenic factors leading to endothelial cell and pericyte differentiation. J Tissue Eng Regen Med. 12(3):775-783.  
  5. Joensuu K, Uusitalo L, Alm JJ, Aro HT, Hentunen TA, Heino TJ (2015) Enhanced osteoblastic differentiation and bone formation in co-culture of human bone marrow mesenchymal stromal cells and peripheral blood mononuclear cells with exogenic VEGF. Orthopaedics & Traumatology: Surgery & Research 101(3):381-386. 

Links 

Pekka Hänninen: Laboratory of Biophysics
Kaisa Ivaska-Papaioannou: Bone and energy metabolism

Kaisa Ivaska, PhD, University Lecturer, Adjunct Professor of Cell Biology 

Contact: kaisa.ivaska@utu.fi 

Description of Research 

Our research focuses on the crosstalk between bone metabolism and energy metabolism. Bone is not only a structural organ but interacts with other cell types in the bone marrow microenvironment and also exerts endocrine functions via secreted factors. Our goal is to get insight into bioenergetics of skeletal cells, and to understand how changes in energy metabolism affect bone cells and microenvironment, bone-derived hormones and bone turnover. We use mainly cell culture and cell-based methods, but also human samples obtained from clinical collaborators. 

Current topics 

  • Role of bone-derived hormones (osteokines) in regulating local and whole body energy metabolism 
  • Interactions between bone cells and bone marrow adipocytes in bone microenvironment 
  • The effects of type 2 diabetes on bone metabolism 

Research group members 

  • PhD students: Milja Arponen, Ronja Ojala 
  • Other students: Nicko Widjaja, Sana Rais 

Recent key publications  

  1. Arponen M, Brockmann EC, Kiviranta R, Lamminmäki U, Ivaska KK. Recombinant Antibodies with Unique Specificities Allow for Sensitive and Specific Detection of Uncarboxylated Osteocalcin in Human Circulation. Calcif Tissue Int. 2020 Dec;107(6):529-542. 
  2. Ojala R, Motiani KK, Ivaska KK, Arponen M, Eskelinen JJ, Virtanen KA, Löyttyniemi E, Heiskanen MA, U-Din M, Nuutila P, Kalliokoski KK, Hannukainen JC. Bone Marrow Metabolism Is Impaired in Insulin Resistance and Improves After Exercise Training. J Clin Endocrinol Metab 2020 Dec 1;105(12):dgaa516. 
  3. Pham TT, Ivaska KK, Hannukainen JC, Virtanen KA, Lidell ME, Enerbäck S, Mäkelä K, Parkkola R, Piirola S, Oikonen V, Nuutila P, Kiviranta R. Human Bone Marrow Adipose Tissue is a Metabolically Active and Insulin-Sensitive Distinct Fat Depot. J Clin Endocrinol Metab. 2020 Jul 1;105(7):2300-2310. 
  4. Ivaska KK, Huovinen V, Soinio M, Hannukainen JC, Saunavaara V, Salminen P, Helmiö M, Parkkola R, Nuutila P, Kiviranta R. Changes in bone metabolism after bariatric surgery by gastric bypass or sleeve gastrectomy. Bone 2017 Feb;95:47-54 
  5. Ivaska KK, Heliövaara MK, Ebeling P, Bucci M, Huovinen V, Väänänen HK, Nuutila P, Koistinen HA. The effects of acute hyperinsulinemia on bone metabolism. Endocr Connect 2015 Sep;4(3):155-62. 

Links 

Hannu Järveläinen: The extracellular matrix in health and disease

Hannu Järveläinen, MD, PhD, Professor of Internal Medicine 

Contact: hanjar@utu.fi 

Description of Research 

Our research focuses on the role of extracellular matrix (ECM) macromolecules in health and disease. For example, we now know that the ECM is able to control all distinctive features of malignancies, e.g. migration, proliferation and apoptosis of cancer cells. Lately, our main interest has been the function of a small leucine-rich proteoglycan, decorin, in carcinomas and sarcomas. We are currently working on constructing decorin-based gene vectors as an adjuvant therapy for malignant diseases. This work is performed together with our collaborators in the University of Turku and Åbo Academi. In addition to malignant diseases, we are also investigating the role of ECM macromolecules in cardiovascular pathology, particularly in diabetic macroangiopathy. Altogether, our research sheds light on the initiation and progression of various disease processes, particularly malignancies and cardiovascular diseases, and aims to develop novel ECM-based therapeutic tools to disrupt them.   

Current topics 

  • Function of ECM macromolecules in disease processes, particularly in malignancies and cardiovascular diseases such as diabetic macroangiopathy 
  • Development of novel decorin-based gene vectors as a novel adjuvant therapy for human carcinomas and sarcomas 
  • Pharmacotherapeutic regulation of angiogenic processes 

Research group members 

  • Senior researchers: Annele Sainio, Marie Nyman 
  • PhD students: Jussi Palomäki, Merja Laine 
  • Other students: Juho Mattila, Katariina Huhtala,   
  • Technicians: Merja Lakkisto, Mika Savisalo  

Recent key publications 

  1. Sainio A, Järveläinen H. Extracellular matrix-cell interactions: Focus on therapeutic applications. Cell Signal. 2020; 66:109487 
  2. Sainio A, Takabe P, Oikari S, Salomäki-Myftari H, Koulu M, Söderström M, Pasonen-Seppänen S, Järveläinen H. Metformin decreases hyaluronan synthesis by vascular smooth muscle cells. J Investig Med. 2020; 68:383-391 
  3. Nyman MC, Jokilammi AB, Boström PC, Kurki SH, Sainio AO, Grenman SE, Orte KJ, Hietanen SH, Elenius K, Järveläinen HT. Decorin Expression in human vulva carcinoma: Oncosuppressive fffect of decorin cDNA transduction on carcinoma Cells. J Histochem Cytochem. 2019; 67:511-522 
  4. Sainio AO, Järveläinen HT. Decorin-mediated oncosuppression - a potential future adjuvant therapy for human epithelial cancers. Br J Pharmacol. 2019; 176:5-15 
  5. Boström P, Sainio A, Eigėlienė N, Jokilammi A, Elenius K, Koskivuo I, Järveläinen H. Human metaplastic breast carcinoma and decorin. Cancer Microenviron. 2017; 10:39-48 

Links 

Jukka Kero: Molecular Mechanisms of Thyroid Disorders: from Human Diseases to Mouse Models
Riku Kiviranta: Molecular regulation of bone metabolism
Noora Kotaja: RNA regulation in male germ cells

Noora Kotaja, PhD, Professor of Molecular Medicine

Contact: nookot@utu.fi                                                       

Description of Research

Our research focuses on the mechanisms of spermatogenesis and germline-mediated epigenetic inheritance. In particular, we are interested in the epigenetic and posttranscriptional regulation of gene expression in meiotic and post-meiotic male germ cells, the role of sperm-borne RNAs in transmitting information about acquired condition - to offspring. We use mainly mouse as a model, but we are also actively collaborating with cohort studies to translate our results to humans. Altogether, our research provides important novel insights into our understanding of male infertility and the potential contribution of father’s preconception lifestyle and environmental exposures on offspring health.

Current topics

  • Function of germ cell-specific ribonucleoprotein granules (= germ granules) in posttranscriptional control of gene expression during spermatogenesis
  • Mechanisms of sperm RNA-mediated epigenetic inheritance of metabolic disorders
  • Function of germ cell-specific RNA regulatory mechanism in cancer progression

Research group members

  • Senior researchers: Juho-Antti Mäkelä, Mari Lehti, Matthieu Bourgery
  • PhD students: Ram Prakash Yadav, Tiina Lehtiniemi, Opeyemi Olotu, Margareeta Mäkelä, Lin Ma
  • Other students: Salli Kärnä, Samuli Laasanen
  • Technicians: Anna Puisto

Recent key publications

  1. Yadav RP, Mäkelä JA, Hyssälä H, Cisneros-Montalvo S, Kotaja N. DICER regulates the expression of major satellite repeat transcripts and meiotic chromosome segregation during spermatogenesis. Nucleic Acids Res. 2020 Jul 27;48(13):7135-7153.
  2. Da Ros M, Lehtiniemi T, Olotu O, Meikar O, Kotaja N. Enrichment of Pachytene Spermatocytes and Spermatids from Mouse Testes Using Standard Laboratory Equipment. J Vis Exp. 2019 Sep 17;(151).
  3. Pandey RR, Homolka D, Olotu O, Sachidanandam R, Kotaja N, Pillai RS. Exonuclease Domain-Containing 1 Enhances MIWI2 piRNA Biogenesis via Its Interaction with TDRD12. Cell Rep. 2018 Sep 25;24(13):3423-3432.e4.
  4. Lehtiniemi T, Kotaja N. Germ granule-mediated RNA regulation in male germ cells. Reproduction. 2018 Feb;155(2):R77-R91.
  5. Da Ros M, Lehtiniemi T, Olotu O, Fischer D, Zhang FP, Vihinen H, Jokitalo E, Sironen A, Toppari J, Kotaja N. FYCO1 and autophagy control the integrity of the haploid male germ cell-specific RNP granules. Autophagy. 2017 Feb;13(2):302-321.

Links

Tiina Laitala: Tissue healing after trauma (THAT)
Jonne Laurila: Molecular pharmacology of hyman alpha2-adrenoceptors and octopamine receptors

Jonne Laurila, PhD, University Teacher, Adjunct Professor of Pharmacology 

Contact: jomila@utu.fi 

Description of Research 

Our research focuses on the molecular pharmacology of human alpha2-adrenoceptors and octopamine receptors of the barnacle Balanus improvises. Octopamine receptors of insects represent counterparts of the adrenoceptors in vertebrate animals. The [Symbol]2-adrenoceptor agonist medetomidine, known as a veterinary sedative agent, was discovered to inhibit the settling process of barnacles by inducing hyperactivity in the barnacle larvae. Our interest is to identify new compounds that are able to activate either octopamine receptors of the barnacle Balanus improvises or the [Symbol]2-adrenoceptors of vertebrates. We have developed novel cell-based screening and profiling assays to identify selective compounds for these receptors. 

Current topics 

  • Screening subtype selective compounds for the human alpha2-adrenoceptors and octopamine receptors of the barnacle Balanus improvises 
  • Improving the molecular-level understanding of the structural determinants of selectivity both at human alpha2-adrenoceptors and octopamine receptors of the barnacle Balanus improvises 

Research group members 

  • Senior researchers: Mika Scheinin  
  • Technicians: Hanna Haukkala 

Recent key publications 

  1. Dikic T, Vucicevic J, Laurila J, Radi M, Veljkovic N, Xhaard H, Nikolic K (2020). Deciphering Imidazoline Off-targets by fishing in the class A of GPCR field. Mol Inform. 39(7):e1900165. 
  2. LindU, Alm Rosenblad M, Hasselberg FL, Falkbring S, Brive L, Laurila JM, Pohjanoksa K, Vuorenpää A, Kukkonen JP, Gunnarsson L, Scheinin M, Mårtensson Lindblad LG, Blomberg A (2010). Octopamine receptors from the barnacle Balanus improvisus are activated by the [Symbol]2-adrenoceptor agonist medetomidine. Mol Pharmacol. 78: 237-48. 
  3. Ruuskanen JO, Laurila J, Xhaard H, Rantanen VV, Vuoriluoto K, Wurster S, Marjamäki A, Vainio M, Johnson MS, Scheinin M (2005). Conserved structural, pharmacological and functional properties among the three human and five zebrafish [Symbol]2-adrenergic receptors. Brit J Pharmacol. 144:165-77. 
  4. Laurila JM, Xhaard H, Ruuskanen JO, Rantanen MJ, Karlsson HK, Johnson MS, Scheinin M (2007). The second extracellular loop of [Symbol]2A-adrenoceptors contributes to the binding of yohimbine analogues. Brit J Pharmacol. 151: 1293-304. 
  5. Laurila JM, Wissel G, Xhaard H, Ruuskanen J, Johnson MS, Scheinin M (2011). Involvement of the first transmembrane segment of human α2-adrenoceptors in the subtype-selective binding of chlorpromazine, spiperone and spiroxatrine. Brit J Pharmacol. 164: 1558-72. 

Links 

Arto Liljeblad: Enzymatic preparation of radiopharmaceuticals for PET imaging
Kirsi Laitinen: Early Nutrition and Health

Kirsi Laitinen, PhD, Associate Professor of Human Nutrition 

Contact: kirsi.laitinen@utu.fi 

Description of Research 

The goal of the research group is to provide a scientific basis for the relationship between diet and health, including mechanistic studies, focusing on the effects of maternal nutrition, metabolism and gut microbiome on both maternal and child health. We consider it of importance to evaluate the interactions between diet, metabolism and microbiome in defining clinical health outcomes, including body composition as well as behavioural fafctors, as part of a holistic approach. ​ 

Current topics 

  • Long-term impacts of diet and fish oil and/or probiotics consumption during pregnancy on maternal and child health  
  • Long-term impacts of diet, microbiome metagenomics and metabolomics interaction on maternal and child health 
  • Early determinants of eating behavior: A multifactorial approach on obesity prevention in children 
  • E-health technologies as novel means in supporting lifestyle changes 

Research group members 

  • Senior researchers: Kati Mokkala, Kristiina Tertti, Outi Pellonperä 
  • PhD students: Noora Houttu, Ella Koivuniemi, Mrunalini Lotankar,  
  • Other students: Ella Muhli, Jenni Soukka, Tyti Hämeenaho, Mira Minkkinen, Laura Näsänen, Heidi Haataja  

Recent key publications  

  1. Mokkala K, Paulin N, Houttu N, Koivuniemi E, Pellonperä O, Khan S, Pietilä S, Tertti K, Elo LL, Laitinen K. Metagenomics analysis of gut microbiota in response to diet intervention and gestational diabetes in overweight and obese women: a randomized, double-blind, placebo-controlled clinical trial. Gut 2020 (published online: August 25, 2020). Doi: 10.1136/gutjnl-2020-321643 
  2. Gerdes V, Gueimonde M, Pajunen L, Nieuwdorp M, Laitinen K. How strong is the evidence that gut microbiota composition can be influenced by lifestyle interventions in a cardio-protective way? Atherosclerosis 2020. https://doi.org/10.1016/j.atherosclerosis.2020.08.028  
  3. Pellonperä O, Mokkala K, Houttu N, Vahlberg T, Koivuniemi E, Tertti K, Rönnemaa T, Laitinen K. Efficacy of fish oil and/or probiotic intervention on the incidence of gestational diabetes in an at-risk group of overweight and obese women – a randomized, placebo-controlled, double-blind clinical trial. Diabetes Care 2019;42:1009-1017. https://doi.org/10.2337/dc18-2591    
  4. Mokkala K, Vahlberg T, Pellonperä O, Houttu N, Koivuniemi E, Laitinen K. Distinct metabolic profile in early pregnancy of overweight and obese women developing gestational diabetes. J Nutr 2019;150:31-37. pii: nxz220. doi: 10.1093/jn/nxz220 doi.org/10.1093/jn/nxz220 
  5. Houttu N, Kalliomäki M, Grönlund M-M, Niinikoski H, Nermes M, Laitinen K. Body composition in children with chronic inflammatory diseases: A systematic review. Clinical Nutrition 2020;39:2647-2662. https://doi.org/10.1016/j.clnu.2019.12.027   

Links 

Timo Myöhänen: Novel multitargeting therapies for neurodegenerative diseases

Timo Myöhänen, PhD, Assistant Professor of Drug Development and Disease Modelling

Contact: timo.myohanen@utu.fi

Description of Research

My team is focused on finding and developing novel therapies for neurodegenerative diseases. Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, are devastating diseases where neuronal degeneration in the brain causes different symptoms such as dementia and movement disorders. Neuronal death progresses within the disease, causing more severe symptoms, and current therapies cannot block or even delay this process. Our goal is to find drug targets that have multitargeting features on various toxic mechanisms that are common in neurodegenerative diseases, and develop small-molecular molecules on these.

Current topics

  • Novel prolyl oligopeptidase (PREP) ligands to block protein aggregation in preclinical models of neurodegenerative diseases
  • MID1 protein as a drug target in neurodegenerative diseases

Research group members

  • Novel group actively seeking funding to establish a research group in University of Turku.

Recent key publications

  1. Myöhänen TT, Hannula MJ, Van Elzen R, Gerard M, Van Der Veken P, Baekelandt V, Garcia-Horsman JA, Männistö PT, Lambeir AM: The prolyl oligopeptidase inhibitor, KYP-2047, reduces α-synuclein protein levels and aggregates in cellular and animal models of Parkinson’s disease. British Journal of Pharmacology, 166: 1097-113, 2012.
  2. Savolainen MH, Richie C, Harvey BK, Männistö PT, Maguire-Zeiss KA, Myöhänen TT: The beneficial effect of a prolyl oligopeptidase inhibitor, KYP-2047, on alpha-synuclein clearance and autophagy in A30P transgenic mouse. Neurobiology of disease 68C:1-15, 2014
  3. Svarcbahs R, Julku UH, Myöhänen TT: Inhibition of Prolyl Oligopeptidase restores spontaneous motor behavior in alpha-synuclein virus vector based Parkinson's disease mouse model by decreasing alpha-synuclein oligomeric species in mouse brain. Journal of Neuroscience 36: 12485-12497, 2016
  4. Svarcbahs R, Jäntti M, Kilpeläinen T, Julku U Urvas L, Kivioja S, Norrbacka S, Myöhänen TT: Prolyl oligopeptidase inhibition activates protein phosphatase 2A. Pharmacological Research 151: 104558, 2020
  5. Kilpeläinen T, Hellinen L, Vrijdag J, Yan X, Svarcbahs R, Vellonen KS, Lambeir AM, Huttunen H, Urtti A, Wallen EAA, Myöhänen TT: The effect of prolyl oligopeptidase inhibitors on alpha-synuclein aggregation and autophagy cannot be predicted by their inhibitory efficacy. Biomedicine & Pharmacotherapy 128:110253, 2020

Links

Sari Mäkelä: Diet and cancer
Jorma Määttä: Myeloid cells in regulation of chronic inflammation, autoimmunity and tumor microenvironment

Jorma Määttä, PhD, University Lecturer, Adjunct Professor of Molecular Cell Biology 

Contact: jmaatta@utu.fi 

Description of Research 

In my research, the function of myeloid cells and mesenchymal cells in the process of calvarial implant integration (ADMIO-consortium). Further, we study also the role of sex steroid receptors on regulation of myeloid cells. This includes the role of myeloid cells in chronic inflammations (e.g. chronic colitis) as well as in tumors. 

Current topics 

  • Sex steroid receptor-mediated regulation of myeloid cells and tissue-level immune reactions 
  • Myeloid cells in implant healing and ossification 
  • Myeloid cells in breast and prostate cancer biology 

Research group members 

  • PhD students: Karoliina Suominen, Santeri Anttila, Hristo Zlatev 
  • Other students: Anja Hjelt 

Recent key publications  

  1. Pekka K. Vallittu, Jussi P. Posti, Jaakko M. Piitulainen, Willy Serlo, Jorma A. Määttä, Terhi J. Heino, Stefania Pagliari, Stina M. Syrjänen, Giancarlo Forte (2020) Biomaterial and implant induced heterotopic ossification: in vitro and in vivo findings. Journal of Tissue Engineering and Regenerative Medicine.  14,1157-1168. 
  2. Lauri Polari, Santeri Anttila, Terhi Helenius, Anu Wiklund, Tero Linnanen, Diana M. Toivola, Jorma Määttä (2019) Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis. International Journal of Molecular Sciences, Jun 20;20(12). pii: E3007. doi: 10.3390/ijms20123007. 
  3. Lauri Polari, Anu Wiklund, Sofia Sousa, Lauri Kangas, Tero Linnanen, Pirkko Härkönen, Jorma Määttä (2018) SERMs promote anti-inflammatory signaling and phenotype of CD14+ cells. Inflammation, 41, 1157-1171 [Springer Nature] 
  4. Bendre A, Moritz N, Väänänen V, Määttä JA (2018) Dicer1 ablation in osterix positive bone forming cells affects cortical bone homeostasis. Bone, 106, 139-147 
  5. Sofia Sousa, Régis Brion, Minnamaija Lintunen, Pauliina Kronqvist, Jouko Sandholm, Jukka Mönkkönen, Pirkko-Liisa Kellokumpu-Lehtinen, Susanna Lauttia, Olli Tynninen, Heikki Joensuu, Dominique Heymann, Jorma Määttä. (2015) Human breast cancer cells educate macrophages toward the M2 activation status. Breast Cancer Research, 17:101 

Links 

Harri Niinikoski: Childhood nutrition and metabolism

Harri Niinikoski, MD, PhD, Professor of Nutrition in Medicine 

Contact: hjniin@utu.fi 

Description of Research 

My research interest focuses on childhood nutrition and metabolism and their connections with non-communicable diseases. In STRIP study, we have for almost 3 decades investigated the effects of childhood diet on later atherosclerosis development in a randomized controlled manner. Moreover, we actively investigate LPI, i.e. lysinuric protein intolerance, one of the most common diseases of the Finnish disease heritage. In DIARA2, we explore the effects of maternal metformin use in offspring’s metabolism. We have also started a study of congenital hypothyroidism in Finland.  Furthermore, I’m have been part of the national neonatal metabolic screening team since its beginning in 2007. Most of the studies connect basic research with active clinical component. 

Current topics 

  • Effects of early nutrition on growth and metabolism in adulthood 
  • Effects of metformin in gestational diabetes on offspring glucose and lipid metabolism 
  • Eenal and clotting problems in LPI  
  • Optimal treatment of congenital hypothyroidism 

Research group members 

  • PhD students: Mari Kärki, Elisa Paavilainen, Laura Niuro, Lotta Pajunen 

Recent key publications 

  1. Pahkala K, Laitinen TT, Niinikoski H, et al. Effects of 20-year infancy-onset dietary counselling on cardiometabolic risk factors in the Special Turku Coronary Risk Factor Intervention Project (STRIP): 6-year post-intervention follow-up. Lancet Child Adolesc Health 2020;4,359-69 
  2. Warrington NM, Beaumont RN, Horikoshi M, et al. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors. Nat Genet. 2019;51(5):804-814 
  3. Nunes V, Niinikoski H. Lysinuric Protein Intolerance. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. 2018 Apr 12 
  4. Pitkänen HH, Kärki M, Niinikoski H, et al. Abnormal coagulation and enhanced fibrinolysis due to lysinuric protein intolerance associates with bleeds and renal impairment. Haemophilia. 2018;24:e312-21 
  5. Horikoshi M, Beaumont RN, Day FR, et al. Genome-wide associations for birth weight and correlations with adult disease. Nature. 2016;538(7624):248-52

Links 

Olli Pentikäinen: MedChem.fi: Computer-dependent drug discovery

Olli Pentikäinen, PhD, Professor of Medicinal Chemistry 

Contact: olli.pentikainen@utu.fi 

Description of Research 

Our goal is to develop a cost-efficient platform for drug discovery, especially to target protein-protein interactions with small molecules. To reach this goal, we develop and utilize novel computational methods and software tools to understand the target protein motion and ligand recognition broadly enough to identify active ligands from the large small-molecule databases successfully. Identified hit molecules could then be optimized towards clinical candidates using, e.g., virtual synthesis with deep learning/artificial intelligence techniques. 

Current topics 

  • Development of drug discovery platform 
  • Rational discovery of small molecule protein-protein interaction modulators 
  • Development of pro-fluorescent tool compounds 
  • Identification of druggable protein conformations 

Research group members 

  • Senior researchers: Sanna Niinivehmas, Krishnasamy Gopinath, Pankaj Kumar Singh  
  • PhD students: Mira Ahinko, Elmeri Jokinen, Sami Kurkinen, Sakari Lätti 
  • Other students: Kseniia Petrova-Szczasiuk 

Recent key publications  

  1. Niinivehmas S, Postila PA, Rauhamäki S, Manivannan E, Kortet S, Ahinko M, Huuskonen P, Nyberg N., Koskimies P, Lätti S, Multamäki E, Juvonen RO, Raunio H, Pasanen M, Huuskonen J, Pentikäinen OT. Blocking oestradiol synthesis pathways with potent and selective coumarin derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry. 2018, 33:743-754. 
  2. Jokinen EM, Postila PA, Ahinko M, Niinivehmas S, Pentikäinen OT. Fragment- and Negative Image-Based Screening of Phosphodiesterase 10A Inhibitors. Chemical Biology & Drug Design. 94: 1799-1812. 
  3. Kurkinen S, Lätti S, Pentikäinen OT, Postila PA. Getting Docking into Shape Using Negative Image-Based Rescoring. Journal of Chemical Information and Modeling. 59: 3584-3599. 
  4. Rauhamäki S, Postila PA, Niinivehmas S, Kortet S, Schildt E, Pasanen Mi, Manivannan E, Ahinko M, Koskimies P, Nyberg N, Huuskonen P, Multamäki E, Pasanen Ma, Juvonen RO, Raunio H, Huuskonen J, Pentikäinen OT. Structure-Activity Relationship Analysis of 3-phenylcoumarin-Based Monoamine Oxidase B Inhibitors. Frontiers in Chemistry, 2018, https://doi.org/10.3389/fchem.2018.00041 
  5. Juvonen RO, Ahinko M, Huuskonen J, Raunio H, Pentikäinen OT. Development of New Coumarin-Based Profluorescent Substrates for Human Cytochrome P450 Enzymes. Xenobiotica. 49: 1015-1024. 

Links 

Ulla Pentikäinen: Molecular Mechanisms of Diseases

Ulla Pentikäinen, PhD, University Lecturer, Adjunct Professor of Biochemistry 

Contact: ulla.pentikainen@utu.fi 

Description of Research 

Protein phosphatase 2A (PP2A) complexes function as tumor suppressors by inhibiting several critical oncogenic signaling pathways. The increased expression of different endogenous PP2A inhibitor proteins has been related to various cancer types lacking efficient therapies. Accordingly, there is a need for more effective treatment strategies. Our ultimate aim is the development of new therapeutics for PP2A related cancer types. Towards this aim, we need to understand the molecular and structural framework of PP2A inhibition. We combine various structural biology methods with computational and biophysical methods to characterize the molecular and structural level mechanism of inhibitor protein mediated PP2A inhibition.   

Current topics 

  • Structural characterization of PP2A inhibitor proteins 
  • The understanding the molecular and structural level mechanism of inhibitor protein mediated PP2A inhibition   
  • The development of small molecular modulators that inhibit PP2A – inhibitor protein interaction 

Research group members 

  • Senior researchers: Hanna Parkkola 
  • PhD students: Pekka Roivas, Chandan Thapa  

Recent key publications  

  1. Thapa, C. J., Haataja, T., Pentikäinen, U., and Permi, P. (2020) 1H, 13C and 15N NMR chemical shift assignments of cAMP-regulated phosphoprotein-19 and -16 (ARPP-19 and ARPP-16). Biomol. NMR Assign 
  2. Haataja, T. J. K., Capoulade, R., Lecointe, S., Hellman, M., Merot, J., Permi, P., and Pentikäinen, U. (2019) Critical Structural Defects Explain Filamin A Mutations Causing Mitral Valve Dysplasia. Biophys. J.  
  3. Haataja, T. J. K., Bernardi, R. C., Lecointe, S., Capoulade, R., Merot, J., and Pentikäinen, U. (2019) Non-syndromic Mitral Valve Dysplasia Mutation Changes the Force Resilience and Interaction of Human Filamin A. Structure. 27, 1–11 
  4. Tossavainen, H., Raulinaitis, V., Kauppinen, L., Pentikäinen, U., Maaheimo, H., and Permi, P. (2018) Structural and Functional Insights Into Lysostaphin–Substrate Interaction. Front. Mol. Biosci. 5, 1–14 
  5. Seppälä, J., Bernardi, R. C., Haataja, T. J. K., Hellman, M., Pentikäinen, O. T., Schulten, K., Permi, P., Ylänne, J., and Pentikäinen, U. (2017) Skeletal Dysplasia Mutations Effect on Human Filamins ’ Structure and Mechanosensing. Sci. Rep. 7, 4218 

Links 

Ullamari Pesonen: Neurodegenerative diseases and brain metabolism

Ullamari Pesonen, PhD, Professor of Pharmacology and Drug Development 

Contact: ullamari.pesonen@utu.fi 

Description of Research 

Defects in insulin signalling and insulin resistance seems to be one of the major hallmarks in the pathogenesis of Alzheimer’s disease (AD). Type 2 diabetes (T2D) is a well-known risk factor for AD, and already very early events in AD pathogenesis include both insulin resistance and altered glucose utilization and metabolism. To study the insulin pathways in periphery and CNS we use transgenic animal model and in vitro studies. Since pathology of AD seems have a major metabolic component, the development of secondary interventions for persons with higher risk to develop AD is crucial. Activating centrally insulin signalling pathway with insulin-sensitizing CNS penetrating drugs could be an effective strategy to protect neurons and synapses from Aβ toxicity in a preventive manner. 

Current topics 

  • Alzheimer’s disease (AD) and metabolic disturbances in brain 
  • Type 2 diabetes as a risk factor to AD 
  • Pharmacology of pain and analgesia 
  • Rare aggregation diseases 

Research group members 

  • PhD students: Laura Leimu, Tiina Leino, Jyrki Lehtimäki, Sammeli Liikkanen 

Recent key publications  

  1. T. Leino, J. Lehtimäki, A. Koivisto, A. Haapalinna, U. Pesonen. Fadolmidine – Favourable adverse effects profile for spinal analgesia suggested by in vitro and in vivo models. Eur J Pharmacol 882, 2020 
  2. M. Kolkka, H. Forssell, A. Virtanen, A. Puhakka, U. Pesonen, and S.K. Jääskeläinen. Neurophysiology and genetics of burning mouth syndrome. Eur J Pain 23, 1153-1161, 2019 
  3. H. Salomäki-Myftari, L.H. Vähätalo, L. Ailanen, S. Pietilä, A. Laiho, A. Hänninen, E. Munukka, E. Savontaus, U. Pesonen and M. Koulu. Neuropeptide Y overexpressing female and male mice show divergent metabolic but not gut microbial responses to prenatal metformin exposure. PLoS One 11(9):e0163805, 2016 
  4. C.-H. Fabritius, U. Pesonen, J. Messinger, R. Horvath, H. Salo, M. Gałęzowski, M. Galek, K. Stefanska, J. Szeremeta-Spisak, M. Olszak-Płachta, A. Buda, J. Adamczyk, M. Krol, P. Prusis, M. Sieprawska-Lupa, M.Mikulski, K. Kuokkanen, H. Chapman, R. Obuchowicz, T. Korjamo, N. Jalava and M. Nowak. 1-Sulfonyl-6-Piperazinyl-7-Azaindoles as potent and pseudoselective 5-HT6 receptor antagonists. Bioorg. Medicinal Chem. Lett. 26, 2610–2615, 2016 
  5. M. Kovalainen, J. Mönkäre, J. Riikonen, U. Pesonen, M. Vlasova, J. Salonen, V.P. Lehto, K. Järvinen, K.H. Herzig. Novel Delivery Systems for Improving the Clinical Use of Peptides. Pharmacol Rev. 67, 541-561, 2015 

Links 

Matti Poutanen: Sex steroid-dependent diseases

Matti Poutanen, PhD, Professor of Physiology 

Contact: matpou@utu.fi 

Description of Research 

My research group has been internationally in a key position in providing evidence for the concept where the ligand concentration available for steroid hormone receptor binding is markedly regulated by the target tissue metabolism, termed intracrine steroid hormone action. The concept has proven to be essential for the growth and progression of both prostate and breast cancer. We, furthermore, have shown this concept to be valid also in premenopausal women, eg. in the endometrium and endometriosis, and other medically relevant implications are expected to rise in the near future. 

Current topics 

  • Development and progression of nonalcoholic fatty liver disease 
  • Endometrial function and endometrial disorders 
  • Hormone-dependent cancer: Breast and prostate cancer 
  • Reproductive physiology of gonads and accessory sex glands 

Research group members 

  • Senior researchers: Leena Strauss, Niina Saarinen-Aaltonen, Taija Heinosalo, Kalle Rytkönen, Guillermo Martinez-Nieto  
  • PhD students: Hanna Heikelä, Michael Gabriel, Arttu Junnila, Laura Marinoja 

Recent key publications  

  1. Gabriel M, Fey V, Heinosalo T, Adhikari P, Rytkönen K, Komulainen T, Huhtinen K, Laajala TD, Siitari H, Virkki A, Suvitie P, Kujari H, Aittokallio T, Perheentupa A, Poutanen M. A relational database to identify differentially expressed genes in the endometrium and endometriosis lesions. Sci Data. 2020 Aug 28;7(1):284.  
  2. Heikelä H, Ruohonen ST, Adam M, Viitanen R, Liljenbäck H, Eskola O, Gabriel M, Mairinoja L, Pessia A, Velagapudi V, Roivainen A, Zhang FP, Strauss L, Poutanen M. Hydroxysteroid (17β) dehydrogenase 12 is essential for metabolic homeostasis in adult mice. Am J Physiol Endocrinol Metab. 2020 Sep 1;319(3):E494-E508 
  3. Sipilä P, Junnila A, Hakkarainen J, Huhtaniemi R, Mairinoja L, Zhang FP, Strauss L, Ohlsson C, Kotaja N, Huhtaniemi I, Poutanen M. The lack of HSD17B3 in male mice results in disturbed Leydig cell maturation and endocrine imbalance akin to humans with HSD17B3 deficiency. FASEB J. 2020 May;34(5):6111-6128.  
  4. Huhtaniemi R, Oksala R, Knuuttila M, Mehmood A, Aho E, Laajala TD, Nicorici D, Aittokallio T, Laiho A, Elo L, Ohlsson C, Kallio P, Mäkelä S, Mustonen MVJ, Sipilä P, Poutanen M. Adrenals Contribute to Growth of Castration-Resistant VCaP Prostate Cancer Xenografts. Am J Pathol. 2018 Dec;188(12):2890-2901.  
  5. Heinosalo T, Gabriel M, Kallio L, Adhikari P, Huhtinen K, Laajala TD, Kaikkonen E, Mehmood A, Suvitie P, Kujari H, Aittokallio T, Perheentupa A, Poutanen M. Secreted frizzled-related protein 2 (SFRP2) expression promotes lesion proliferation via canonical WNT signaling and indicates lesion borders in extraovarian endometriosis. Hum Reprod. 2018 May 1;33(5):817-831. 

Links 

Nafis Rahman: Novel Treatment Strategies for Endocrine Tumors

Nafis Rahman, MD, PhD, Clinical Lecturer, Adjunct Professor of Physiology 

Contact: nafrah@utu.fi 

Description of Research 

We study the underlying molecular mechanisms of hormonally regulated cancers (i.e. prostate, ovarian, testicular and adrenocortical) and other diseases related to reproductive sciences, search for their novel biomarkers and treatment. We recently tested the potential of tumor specific zona pellucida antigen-3 immunization to enhance therapeutic effects in several hormonally regulated cancers. We have used successfully conjugated lytic peptides to eradicate only cancer cells through their specific gonadotropin receptors (such as lhcgr). We use transgenic murine endocrine cancer metastatic disease models and immortalized cell lines to test the feasibility of novel treatment strategies starting at cellular, in vivo in TG mice and finally aim for human clinical trials. Current Research topics /fields: hormonally regulated cancers; prostate, ovarian, adrenocortical & gonadal cancers and novel biomarkers; gonadotropins and their receptors; estrogen actions on fertility; immunotherapy and receptor-targeted conjugated lytic peptides as cancer drugs; transgenic murine models for human diseases. 

Current topics 

  • Functional implications of zona pellucida 3 expression in cancer and its potential as a biomarker 
  • Molecular pathomechanisms underlying the polycystic ovarian syndrome 
  • hormonally regulated cancers and reproductive age diseases (eg. Endometriosis, myoma uteri) 
  • Gonadotropins and their receptors 

Research group members 

  • Senior researchers: Donata Ponikwicka-Tyszko 
  • PhD students: Kamila Pulawska 

Recent key publications

  1. Ponikwicka-Tyszko D, Chrusciel M, Pulawska K, Bernaczyk P, Sztachelska M, Guo P, Li X, Toppari J, Huhtaniemi J, Wolczynski S and Rahman NA*. Mifepristone Treatment Promotes Testicular Leydig Cell Tumor Progression in Transgenic Mice (2020) Cancers In press  
  2. Lukasiewicz M, Czerniecki J, Ponikwicka-Tyszko D, Sztachelska M, Hryniewicka M, Nalewajko-Sieliwoniuk E, Wiczkowski W, Banaszewska B, Milewski R, Toppari J, Huhtaniemi I, Rahman NA, Wolczynski S. Placenta is Capable of Protecting the Male Fetus from Exposure to Environmental Bisphenol A. Exposure and Health 2020 e-pub May 2020 https://link.springer.com/article/10.1007/s12403-020-00358-5  
  3. PonikwickaTyszko D, Chrusciel M, Stelmaszewska J, Bernaczyk P, Chrusciel P, Sztachelska M, Scheinin M, Bidzinski M, Szamatowicz J, Huhtaniemi IT, Wolczynski S, Rahman NA. Molecular mechanisms underlying mifepristone's agonistic action on ovarian cancer progression. EBioMedicine. 2019 Aug 26. pii: S2352-3964(19)30560-2 
  4. Doroszko M, Chrusciel M, Stelmaszewska J, Slezak T, Anisimowicz S, Plöckinger U, Quinkler M, Bonomi M, Wolczynski S, Huhtaniemi I, Toppari J, Rahman NA. (2019) GnRH antagonist treatment of malignant adrenocortical tumors. Endocr Relat Cancer. 2019 Jan 1;26(1):103-117.  
  5. Oduwole OO, Peltoketo H, Ariel Poliandri A, Vengadabady L, Chrusciel M, Doroszko M, Samanta L, Owen L, Keevil B, Rahman NA, Huhtaniemi IT (2018) Androgen-independent spermatogenesis by a constitutively active FSH receptor. J Clin Invest. 2018 May 1;128(5):1787-1792.  

Links 

Petteri Rinne: Melanocortins in cardiovascular health and disease

Petteri Rinne, PhD, Academy Research Fellow, Adjunct Professor of Cardiovascular Pharmacology 

Contact: pperin@utu.fi 

Description of Research 

Melanocortins are known for their central role in skin pigmentation and for their immunomodulatory actions in leukocytes. However, melanocortins appear to have also direct effects on the vasculature and heart. Our current research projects focus on investigating the role of melanocortin signalling in cardiovascular diseases, particularly in atherosclerosis and cardiac hypertrophy. We utilize both loss- and gain-of-function models as well as pharmacological and genetic approaches to advance our understanding of the role of melanocortins and their cognate receptors in these diseases. Ultimately, the research aims at evaluating the therapeutic potential of targeting melanocortin receptors for the management of lipid disorders, atherosclerosis, cardiac hypertrophy. 

Current topics 

  • The role of melanocortin receptors in regulating physiological and pathological cardiac hypertrophy 
  • Melanocortin 1 receptor as a regulator of cholesterol and fatty acid homeostasis in the liver 
  • Anti-inflammatory effects of melanocortins and their role in the development of atherosclerosis  

Research group members 

  • PhD students: James Kadiri, Anni Suominen, Keshav Thapa 
  • Other students: Guillem Saldo Rubio 
  • Technicians: Sanna Bastman, Hanna Haukkala 

Recent key publications  

  1. Kadiri J, Thapa K, Kaipio K, Cai M, Hruby VJ, Rinne P. Melanocortin 3 receptor activation with [D-Trp8]-γ-MSH suppresses inflammation in apolipoprotein E deficient mice Eur J Pharmacol. 2020 Aug 5;880:173186. 
  2. Rinne P, Guillamat-Prats R, Rami M, et al. Palmitoylethanolamide Promotes a Pro-Resolving Macrophage Phenotype and Attenuates Atherosclerotic Plaque Formation. Thromb Vasc Biol. 2018 Nov;38(11):2562-2575.  
  3. Nuutinen S, Ailanen L, Savontaus E, Rinne P. Melanocortin Overexpression Limits Inflammation and Atherosclerosis in LDLR-/- mice.  J Endocrinol. 2018 Mar;236(3):111-123 
  4. Rinne P, Kadiri J, Velasco-Delgado M, Nuutinen S, et al. Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E -/- Mice. Arterioscler Thromb Vasc Biol. 2018 Feb;38(2):313-323. 
  5. Rinne P, Rami M, Nuutinen SL, et al. Melanocortin 1 Receptor Signaling Regulates Cholesterol Transport in Macrophages. Circulation. 2017 Jul 4;136(1):83-97. 

Links 

Anne Roivainen: In vivo imaging of inflammation

Anne Roivainen, PhD, Professor of Preclinical Imaging and Drug Research

Contact: aroivan@utu.fi, anne.roivainen@tyks.fi

Description of Research

Inflammation is a significant component of several chronic diseases involving the cardiovascular, metabolic, respiratory, gastrointestinal, musculoskeletal and nervous systems. The timely identification and localization of inflammation is critical for the adequate treatment of patients; however, the currently available methodologies are insufficient to meet these goals. Positron emission tomography (PET) with targeted probes enables evaluation of the molecular and cellular pathophysiological mechanisms of diseases. My team has expertise to develop new radiopharmaceuticals for whole body imaging and quantification of inflammation. Our projects will evaluate the potential of new molecular imaging probes to monitor disease activity and the efficacy of treatment. Noteworthy, the development of new radiopharmaceuticals requires several years’ effort and expensive proof-of-concept studies, and determination of acute toxicity before entering in human studies. My research group works at the Turku PET Centre where we have state-of-art infrastructure to be at the forefront of international development in the field. The results of these studies are expected to provide new tools for molecular imaging and promote the translation of these tools into clinical use. The sensitive whole-body imaging of inflammation will provide useful end-points for early diagnosis, as well as clinical trials testing new therapies. Identification of patients who unlikely respond to therapy early in a course of the treatment could reduce morbidity and produce cost-savings.

Current topics

  • VAP-1 and CLEVER-1 as targets for in vivo imaging of inflammation and cancer
  • Folate receptor targeted imaging agents and treatments in cardiovascular disease models
  • Macrophage ligands as imaging tools
  • Glutamine metabolism accessed with PET

Research group members

  • Senior researchers: Xiang-Guo Li, Päivi Marjamäki, Senthil Palani
  • PhD students: Putri Andriana, Petri Elo, Erika Atencio Herre, Imran Iqbal, Arghavan Jahandideh, Ella Kujala, Maxwell Miner, Olli Moisio, Jussi Mäkilä, Mia Ståhle, Riikka Viitanen, Jenni Virta
  • Other academic: Heidi Liljenbäck
  • Technicians: Aake Honkaniemi

Recent key publications

  1. Viitanen R, Moisio O, Lankinen P, Li X-G, Koivumäki M, Suilamo S, Tolvanen T, Taimen K, Mali M, Kohonen I, Koskivirta I, Oikonen V, Virtanen H, Santalahti K, Autio A, Saraste A, Pirilä L, Nuutila P, Knuuti J, Jalkanen S, Roivainen A. First-in-human [68Ga]Ga-DOTA-Siglec-9 study, a PET ligand targeting vascular adhesion protein 1. J Nucl Med 2020 Aug 17;jnumed.120.250696. https://doi.org/10.2967/jnumed.120.250696
  2. Moisio O, Palani S, Virta J, Elo P, Liljenbäck H, Tolvanen T, Käkelä M, Miner M, Atencio Herre E, Marjamäki P, Örd T, Heinäniemi M, Kaikkonen M, Zhang F, Srinivasarao M, Knuuti J, Low PS, Saraste A, Li X-G, Roivainen A. Radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-Folate for PET imaging of folate receptor β-positive macrophages. Sci Rep 2020 Aug 12;10(1):13593. https://doi.org/10.1038/s41598-020-70394-3
  3. Elo P, Li XG, Liljenbäck H, Helin S, Teuho J, Koskensalo K, Saunavaara V, Marjamäki P, Virta J, Chen Q, Low PS, Knuuti J, Jalkanen S, Airas L, Roivainen A. Folate receptor-targeted positron emission tomography of experimental autoimmune encephalomyelitis in rats. J Neuroinflammation 2019 Dec 3;16(1):252. https://doi.org/10.1186/s12974-019-1612-3
  4. Silvola JMU, Li X-G, Virta J, Marjamäki P, Liljenbäck H, Hytönen JP, Tarkia M, Saunavaara V, Hurme S, Palani S, Hakovirta H, Ylä-Herttuala S, Saukko P, Chen Q, Low PS, Knuuti J, Saraste A, Roivainen A. Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography. Sci Rep 2018 Jun 26;8(1):9720. https://doi.org/10.1038/s41598-018-27618-4
  5. Siitonen R, Pietikäinen A, Liljenbäck H, Käkelä M, Söderström M, Jalkanen S, Hytönen J, Roivainen A. Targeting of vascular adhesion protein-1 by positron emission tomography visualizes sites of inflammation in Borrelia burgdorferi-infected mice. Arthritis Res Ther 2017 Nov 22;19(1):254. https://doi.org/10.1186/s13075-017-1460-4

Links

Eriika Savontaus: Neuroendocrine mechanisms in pathogenesis and therapeutics of cardiometabolic diseases
Mika Scheinin: Pharmacokinetics and biomarkers for drug development
Petra Sipilä: Androgen regulation of male reproductive health

Petra Sipilä, Research Director, Adjunct Professor of Reproductive and Developmental Biology 

Contact: mipela@utu.fi 

Description of Research 

Androgens are important regulators of male reproductive health. Androgen regulation is achieved via androgen receptor (AR) activity and ligand availability in target tissues. We are especially interested in studying mechanisms of androgen regulation of gene expression with the focus on epididymal functions and sperm maturation as well as prostate cancer.  

The Finnish disease heritage contains almost forty rare hereditary diseases. FinnDisMice research consortium focuses on modeling Finnish disease heritage in mouse in order to facilitate understanding of disease pathomechanisms that are causative for these diseases. Our group focus on Cartilage-hair hypoplasia, a disease manifested by growth disorder and defective immunity. 

Current topics 

  • Androgen regulation of epididymal functions. 
  • The impact of androgen receptor SUMOylation on prostate cancer progression. 
  • FinnDisMice: New mouse models as tools for studying Rare diseases of Finnish disease heritage 

Research group members 

  • Senior researchers: Marika Karikoski 
  • PhD students: Arttu Junnila 
  • Other students: Inka Raimoranta 
  • Technicians: Jenni Airaksinen 

Recent key publications   

  1. Björkgren I, Sipilä P. The impact of epididymal proteins on sperm function. Reproduction. 2019 Nov 158(5):R155-R167 
  2. Zhang F-P, Malinen M, Mehmood A, Lehtiniemi T, Jääskeläinen T, Korhonen H, Laiho A, Elo L, Ohlsson C, Kotaja N, Poutanen M, Palvimo J,* Sipilä P.* Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction. Nature Communications 2019 Feb 15;10(1):777.  * equal contribution 
  3. Huhtaniemi R, Oksala R, Knuuttila M, Mehmood A, Aho E, Laajala TD, Aittokallio T, Laiho A, Elo L, Ohlsson C, Kallio P, Mäkelä S, Mustonen MVJ, Sipilä P, Poutanen M. Adrenals contribute to growth of castration-resistant VCaP prostate cancer xenografts. Am J Pathol. 2018 Dec;188(12):2890-2901.  
  4. Björkgren I, Gylling H, Turunen H, Huhtaniemi I, Strauss L, Poutanen M, Sipilä P. Imbalanced lipid homeostasis in the conditional Dicer1 knockout mouse epididymis causes instability of the sperm membrane. FASEB J. 2015 Feb;29(2):433-42.  
  5. Björkgren I, Saastamoinen L, Krutskikh A, Huhtaniemi I, Poutanen M, Sipilä P. Dicer1 ablation in the mouse epididymis causes dedifferentiation of the epithelium and imbalance in sex steroid signaling. PLoS One. 2012;7(6):e38457. 

Links 

Anna-Marja Säämänen: Local and systemic regulation of skeletal tissue development and homeostasis by miRNAs and other factors

Anna-Marja Säämänen, PhD, Laboratory Manager, Adjunct Professor of Cell and Molecular Biology 

Contact: ansaama@utu.fi 

Description of Research 

Genome wide approaches have been used to search for novel factors regulating limb chondrogenesis, endochondral ossification and fracture healing. Recently we have focused on the microRNAs in the local and systemic regulation of mesenchymal stromal cell differentiation and tissue homeostasis.  The team discovered a novel transmembrane proteoglycan gene SNORC (secondary ossification center associated regulator of chondrocyte maturation).  

Current topics 

  • Genome wide approaches to study skeletal tissue homeostasis and fracture healing 

Research group members 

  • PhD students: Matthieu Bourgery 
  • Technicians: Merja Lakkisto 

Recent key publications  

  1. Aging and serum exomiR content in women-effects of estrogenic hormone replacement therapy. Kangas R, Törmäkangas T, Fey V, Pursiheimo J, Miinalainen I, Alen M, Kaprio J, Sipilä S, Säämänen AM, Kovanen V, Laakkonen EK. Sci Rep. 2017 Feb 14;7:42702. doi: 10.1038/srep42702. PMID: 28195143 Free PMC article. 
  2. Defects in chondrocyte maturation and secondary ossification in mouse knee joint epiphyses due to Snorc deficiency. Heinonen J, Zhang FP, Surmann-Schmitt C, Honkala S, Stock M, Poutanen M, Säämänen AM. Osteoarthritis Cartilage. 2017 Jul;25(7):1132-1142. doi: 10.1016/j.joca.2017.03.010. Epub 2017 Mar 18. PMID: 28323137 
  3. Soluble activin type IIB receptor improves fracture healing in a closed tibial fracture mouse model. Puolakkainen T, Rummukainen P, Lehto J, Ritvos O, Hiltunen A, Säämänen AM, Kiviranta R. PLoS One. 2017 Jul 13;12(7):e0180593. doi: 10.1371/journal.pone.0180593. eCollection 2017. PMID: 28704409 Free PMC article. 
  4. Snorc is a novel cartilage specific small membrane proteoglycan expressed in differentiating and articular chondrocytes. Heinonen J, Taipaleenmäki H, Roering P, Takatalo M, Harkness L, Sandholm J, Uusitalo-Järvinen H, Kassem M, Kiviranta I, Laitala-Leinonen T, Säämänen AM. Osteoarthritis Cartilage. 2011 Aug;19(8):1026-35. doi: 10.1016/j.joca.2011.04.016. Epub 2011 May 17. PMID: 21624478 
  5. MicroRNAs regulate osteogenesis and chondrogenesis of mouse bone marrow stromal cells. Suomi S, Taipaleenmäki H, Seppänen A, Ripatti T, Väänänen K, Hentunen T, Säämänen AM, Laitala-Leinonen T. Gene Regul Syst Bio. 2008 Apr 22;2:177-91. doi: 10.4137/grsb.s662. PMID: 19787082 Free PMC article. 

Links 

Manuel Tena-Sempere: Neuroendocrinology of Puberty, Fertility and Metabolism
Mika Teräs: Medical physics research

Mika Teräs, PhD, Professor of Medical Physics  

Contact: teras@utu.fi, mika.teras@tyks.fi 

Description of Research 

Most of the research of our group happens at TUCH, where I am coordinating all Medical Physics activities with 17 Medical Physics Experts 5 MP trainees and around 10 project researchers. Research is coordinated by Senior Medical Physicists (professor + 3 docents) and some are assigned to Physics department, Natural Sciences, UTU. 

Current topics 

  • Radiation dose optimization and dosimetry  
  • Nuclear Medicine Instrumentation and modelling (Teräs and Tommi Noponen) 
  • Magnetic Resonance Imaging (PI Jani Saunavaara) 
  • Radiation Therapy Physics (PI Jani Keyriläinen) 

Research group members 

  • Senior researchers: Jani Keyriläinen, Tommi Noponen, Jani Saunavaara, Virva Saunavaara 
  • PhD students: Kalle Koskensalo, Heli Larjava, Teija Sainio, Samuli Arvola, Risto Hirvilammi, Tommi Kokki, Jani Linden, Reetta Siekkinen, Tuula Tolvanen, Tommi Hälli, Iiro Ranta, Aleksi Saikkonen,  
  • Other students: Toni Niiniviita, Jukka Ihalainen 

Recent key publications  

  1. Jukka Järvinen, Joanna Sierpowska, Teemu Siiskonen, Hannu Järvinen, Tuomas Kiviniemi, Tuomas T Rissanen, Hanna Matikka, Eini Niskanen,  Saija Hurme, Heli R S Larjava, Timo J Mäkelä, Satu Strengell, Markku Eskola, Teuvo Parviainen, Elina Hallinen, Markku Pirinen, Antti Kivelä, Mika Teräs: Contemporary Radiation Doses in Interventional Cardiology: a Nationwide Study of Patient Doses in Finland. Radiation Protection Dosimetry (2019): 1-11. 
  2. Arvola S, Jambor I, Kuisma A, Kemppainen J, Kajander S, Seppänen M, Noponen T: Comparison of standardized uptake value between 99mTc-HDP SPECT/CT and 18F-NaF PET/CT in bone metastases of breast and prostate cancer. EJNMMI Research (2019) 9:6. 
  3. Mojtaba Jafari Tadi, Eero Lehtonen, Jarmo Teuho, Juho Koskinen, Jussi Schultz, Reetta Siekkinen, Tero Koivisto, Mikko Pänkäälä, Mika Teräs, Riku Klén: A Computational Framework for Data Fusion in MEMS-Based Cardiac and Respiratory Gating. Sensors 2019, 19, 4137; doi:10.3390/s19194137. 
  4. Sainio T., Komar G., Saunavaara J., Suomi V., Joronen K., Perheentupa A., Viitala A. ja Blanco Sequeiros R: Wedged gel pad for bowel manipulation during MR-guided high-intensity focused ultrasound therapy to treat uterine fibroids: a case report. Journal of Therapeutic Ultrasound . 2018 Nov 28;6:10. doi: 10.1186/s40349-018-0116-4 
  5. Iiro Ranta, Jarmo Teuho, Jani Linden, Riku Klén, Mika Teräs, Mika Kapanen, Jani Keyriläinen:  Assessment of MRI-Based Attenuation Correction for MRI-Only Radiotherapy Treatment Planning of the Brain. Diagnostics 2020, 10, x; doi: FOR PEER REVIEW 

Links 

Jorma Toppari: The early determinants of reproductive health
Aleksi Tornio: Individualized Drug Therapy: Role of Drug-Drug Interactions and Pharmacogenetics

Aleksi Tornio, PhD, Assistant professor of Clinical Pharmacology and Therapeutics 

Contact: aleksi.tornio@utu.fi 

Description of Research 

Drug response is currently poorly predictable, and many patients experience lack of efficacy or adverse effects. Individual differences in drug response are caused by complex interplay of environmental (e.g. drug interactions) and genetic factors. The aim of our work is to identify and characterize the impact of these individual factors on the response to clinically used drugs. This is achieved by clinical drug research (pharmacokinetic studies in patients and healthy volunteers) and epidemiological studies employing biobank and healthcare register data. The ultimate aim is to improve drug efficacy and safety by taking into account these individual factors. 

Current topics 

  • Development of algorithms to define drug response phenotypes from registry and biobank data to scrutinize pharmacogenetic phenomena. 
  • Studies on implementation of pharmacogenetic testing into clinical practice. 
  • Real-world impact of pharmacogenetic variability and cost-effectiveness of pre-emptive pharmacogenetic testing. 

Research group members 

  • Postdocs: Kristiina Cajanus 
  • Other students: Noora Kulla 

Recent key publications  

  1. Siddiqui MK, Maroteau C, Veluchamy A, Tornio A, Tavendale R, Carr F, Abelega N, Carr D, Bloch K, Hallberg P, Yue QY, Pearson ER, Colhoun HM, Morris AD, Dow E, George J, Pirmohamed M, Ridker PM, Doney ASF, Alfirevic A, Wadelius M, Maitland van der Zee AH, Chasman DI, Palmer CNA on behalf of the PREDICTION-ADR consortium. A common missense variant of LILRB5 is associated with statin intolerance and myalgia. Eur Heart J 2017;38:3569-3575. 
  2. Tornio A, Flynn R, Morant S, Velten E, Palmer CNA, MacDonald TM, Doney ASF. Investigating real-world clopidogrel pharmacogenetics in stroke using a bioresource linked to electronic medical records.  Clin Pharmacol Ther 2018;103:281-286. 
  3. Itkonen MK, Tornio A, Lapatto-Reiniluoto O, Neuvonen M, Neuvonen PJ, Niemi M, Backman JT. Clopidogrel increases dasabuvir exposure with or without ritonavir, and ritonavir inhibits the bioactivation of clopidogrel. Clin Pharmacol Ther 2019;105:219-228 
  4. Ellfolk M, Tornio A, Niemi M, Leinonen MK, Lahesmaa-Korpinen AM, Malm H. Placental transporter-mediated drug interactions and offspring congenital anomalies. Br J Clin Pharmacol 2020;86:868-879 
  5. Hirvensalo P, Tornio A, Launiainen T, Paile-Hyvärinen M, Tapaninen T, Neuvonen M, Backman JT, Niemi M. UGT1A3 and sex are major determinants of telmisartan pharmacokinetics - a comprehensive pharmacogenomic study Clin Pharmacol Ther 2020;108:885-895 

Links 

Mikko Uusi-Oukari: Pharmacology of GABAA receptor subtypes

Mikko Uusi-Oukari, PhD, Laboratory Manager, Adjunct Professor of Biochemical Pharmacology 

Contact: mikuus@utu.fi 

Description of Research 

Our research focuses on pharmacology of GABAA receptor subtypes. In particular, we are interested in positive modulators that show selectivity to distinct receptor subtypes. In mouse models it seems that alpha1 GABAA receptors mediate sedation, while anxiolysis is mediated via alpha2 receptors. We are especially interested in delta GABAA receptors that combine with alpha4 and alpha6 subunits. We use recombinant receptor expression, radioligand binding assays, electrophysiological methods, and behavioral studies to evaluate the selectivity of GABAA receptor modulating compounds in vitro and in vivo.   

Current topics 

  • Modulation of GABAA receptor subtypes by hops compounds 
  • Pharmacology of extrasynaptic delta subunit-containing GABAA receptors 
  • Ethanol potentiation of GABAA receptor subtypes 

Research group members 

  • Senior researchers: Sanna Soini 
  • PhD students: Ali Benkherouf 

Recent key publications

  1. Benkherouf AY, Eerola K, Soini SL, Uusi-Oukari M. Humulone modulation of GABAA receptors and its role in hops sleep-promoting activity. Front Neurosci. 2020 Oct 14; doi: 10.3389/fnins.2020.594708. 
  2. Benkherouf AY, Logrén N, Somborac T, Kortesniemi M, Soini SL, Yang B, Salo-Ahen OMH, Laaksonen O, Uusi-Oukari M. Hops compounds modulatory effects and 6-prenylnaringenin dual mode of action on GABAA receptors. Eur J Pharmacol. 2020 Apr 15;873:172962. 
  3. Benkherouf AY, Soini SL, Stompor M, Uusi-Oukari M. Positive allosteric modulation of native and recombinant GABAA receptors by hops prenylflavonoids. Eur J Pharmacol. 2019 Jun 5;852:34-41.  
  4. Benkherouf AY, Taina KR, Meera P, Aalto AJ, Li XG, Soini SL, Wallner M, Uusi-Oukari M. Extrasynaptic δ-GABAA receptors are high-affinity muscimol receptors. J Neurochem. 2019 Apr;149(1):41-53. 
  5. Uusi-Oukari M, Vähätalo L, Liljeblad A. Modifications of diflunisal and meclofenamate carboxyl groups affect their allosteric effects on GABAA receptor ligand binding. Neurochem Res. 2014 Jul;39(7):1183-91.  

Links 

Petri Vainio: Drugs and traffic