Geenien säätelyn genetiikka taudeissa

Tiedot Ihmiset Julkaisut

Johtajat

Sami Heikkinen

Tutkimusjohtaja

Lääketieteen laitos, Biolääketiede

Tavoitteemme on tunnistaa ja molekyylitasolla selittää geenin säätelytekijöiden toimintaa muokkaavaa ihmisen geneettinen vaihtelua, joka voi vaikuttaa sellaisten osittain perinnöllisten sairauksien kuten tyypin 2 diabeteksen tai Alzheimerin taudin syntyyn. Hyödynnämme metabolisiin sairauksiin kohdistuvassa tutkimuksessamme mm. hiirigenetiikan työkaluja ja genominlaajuisia karttoja geenien ilmentymisestä ja kromatiinin aktiivisuudesta sekä kudos- että yksittäisen solun tasolla, tarkoituksenamme siirtää päälöydökset ihmisen metaboliaan vaikuttavan genetiikan piiriin metaboliareittien säätelyn konservaation kautta. Neurodegeneratiivisten sairauksien osalta teemme laajalti yhteistyötä UEF:n Neuro RC:n tutkimusryhmien kanssa.

Uusien, todella kausaalisten geneettisten muutosten tunnistaminen ja mekanistinen selittäminen tarjoavat työkaluja monitekijäisten sairauksien ennustamiseen, alaluokitteluun ja henkilökohtaisen lääketieteen käyttöön.

Rahoitus

Suomen Akatemia, Diabetestutkimussäätiö, Itä-Suomen yliopisto

Yhteistyö

Luke Norton, FT

University of Texas Health San Antonio
Timo Lakka, PhD, MD

Itä-Suomen yliopisto, Biolääketiede
Arto Mannermaa, PhD

Itä-Suomen yliopisto, Kliininen patologia ja oikeuslääketiede

Avainsanat

epigenetiikka geeniekspressio geenin säätely geneettiset variantit genomiikka kromatiini kromatiini-interaktiot transkription säätely

Johtajat

Sami Heikkinen

Tutkimusjohtaja

Lääketieteen laitos, Biolääketiede

Väitöskirjatutkijat

Juho Mononen

Väitöskirjatutkija

Lääketieteen laitos, Biolääketiede

Julkaisut

65 kappaletta

Geenien säätelyn genetiikka taudeissa

Johtajat

Sami Heikkinen

Yhteistyö

Avainsanat

Johtajat

Sami Heikkinen

Väitöskirjatutkijat

Juho Mononen

Integrative analysis of liver-specific non-coding regulatory SNPs associated with the risk of coronary artery disease

Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure

The debatable presence of PIWI-interacting RNAs in invasive breast cancer

Toxicological transcriptome of human airway constructs after exposure to indoor air particulate matter: In search of relevant pathways of moisture damage-associated health effects

Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells

Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

MicroRNAs Associated With Biological Pathways of Left- And Right-sided Colorectal Cancer

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Abdominal adiposity and cardiometabolic risk factors in children and adolescents: a Mendelian randomization analysis

HAS3-induced extracellular vesicles from melanoma cells stimulate IHH mediated c-Myc upregulation via the hedgehog signaling pathway in target cells

Multi-Ancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

The Diabetes Gene and Wnt Pathway Effector TCF7L2 Regulates Adipocyte Development and Function

Integration of VDR genome wide binding and GWAS genetic variation data reveals co-occurrence of VDR and NF-kappaB binding that is linked to immune phenotypes

NRF2 regulates endothelial glycolysis and proliferation with miR-93 and mediates the effects of oxidized phospholipids on endothelial activation

The Effects of Sequence Variation on Genome-wide NRF2 Binding - New Target Genes and Regulatory SNPs

Gene Expression Mapping of Histone Deacetylases and Co-factors, and Correlation with Survival Time and 1H-HRMAS Metabolomic Profile in Human Gliomas

Patterns of Genome-Wide VDR Locations

SUMOylation modulates the transcriptional activity of androgen receptor in a target gene and pathway selective manner

The mechanisms of genome-wide target gene regulation by TCF7L2 in liver cells

The transcriptional regulator BCL6 participates in the secondary gene regulatory response to vitamin D

Dynamics of 1&#945 ,25-dihydroxyvitamin D3-dependent chromatin accessibility of early vitamin D receptor target genes

Chromatin acetylation at transcription start sites and vitamin D receptor binding regions relates to effects of 1alfa,25-dihydroxyvitamin D3 and histone deacetylase inhibitors on gene expression

Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophages

Proto-oncogene PIM-1 is a novel estrogen receptor target associating with high grade breast tumors

The First Genome-wide View of Vitamin D Receptor Locations and Their Mechanistic Implications

The activation of hepatic and muscle polyamine catabolism improves glucose homeostasis

The gene for the transcription factor BHLHE40/DEC1/stra13 is a dynamically regulated primary target of the vitamin D receptor

Nuclear hormone 1&#945 ,25-dihydroxyvitamin D3 elicits a genome-wide shift in the locations of VDR chromatin occupancy

Activated polyamine catabolism leads to low cholesterol levels by enhancing bile acid synthesis

Partial hexokinase II knocout results in acute ischemia-reperfusion damage in skeletal muscle of male, but not female, mice

The Down-regulation of the Human MYC Gene by the Nuclear Hormone 1&#945 ,25-dihydroxyvitamin D3 is Associated with Cycling of Corepressors and Histone Deacetylases

Enhanced polyamine catabolism alters homeostatic control of white adipose tissue mass, energy expenditure, and glucose metabolism

PPARgamma in human and mouse physiology

Phosphorylation barriers to skeletal and cardiac muscle glucose uptakes in high-fat-fed mice. Studies in mice with a 50 % reduction of hexokinase II

Systematic gene expression mapping clusters nuclear receptors according to their function in the brain

Mice with targeted disruption of spermidine/spermine N1-acetyltransferese gene maintain nearly normal tissue polyamine homeostasis but show signs of insulin resistance upon aging

Polyamine-regulated unproductive splicing and translation of spermidine/spermine N1 -acetyltransferase

Transcriptional targeting of virus-mediated gene transfer by the human hexokinase II promoter

Type I interferon response against viral and non-viral gene transfer in human tumor and primary cell lines

Hexokinase II protein content is a determinant of exercise endurance capacity in the mouse

Analysis of the human hexokinase II promoter in vivo: lack of insulin response within 4.0 kb

Glucose Metabolism in Heterozygous Hexokinase II Knock-out Mice

Hexokinase II partial knockout impairs exercise-stimulated glucose uptake in oxidative muscles of mice

Mutations in the cardiac myosin-binding protein C gene are the predominant cause of familial hypertrophic cardiomyopathy in eastern Finland

Concurrent overexpression of ornithine decarboxylase and spermidine/spermine N1-acetyltransferase further accelerates the catabolism of hepatic polyamines in transgenic mice

Mouse hexokinase II gene: structure, cDNA, promoter analysis, and expression pattern

Hexokinase II-deficient mice: prenatal death of homozygotes without disturbances in glucose tolerance in heterozygotes

The codon 64 polymorphism of the beta3-adrenergic receptor gene is not associated with coronary heart disease or insulin resistance in nondiabetic subjects and non-insulin-dependent diabetic patients

Different regulation of free fatty acid levels and glucose oxidation by the Trp64Arg polymorphism of the beta3-adrenergic receptor gene and the promoter variant (A-3826G) of the uncoupling protein 1 gene in familial combined hyperlipidemia

Glucokinase gene islet promoter region variant (G->A) at nucleotide -30 is not associated with reduced insulin secretion in Finns

Synergistic effect of polymorphisms in uncoupling protein 1 and beta3-adrenergic receptor genes on basal metabolic rate in obese Finns

Variants of the fatty acid-binding protein 2 gene are not associated with coronary heart disease in nondiabetic subjects and in patients with NIDDM

Codon 54 polymorphism of the human intestinal fatty acid binding protein 2 gene is associated with dyslipidemias but not with insulin resistance in patients with familial combined hyperlipidemia

New variants in the glycogen synthase gene (GIn71His, Met416Val) in patients with NIDDM from eastern Finland

Polymorphism of the Beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns

The ala54thr polymorphism of the fatty acid binding protein 2 gene does not influence insulin sensitivity in Finnish nondiabetic and NIDDM subjects

The trp64arg polymorphism of the beta3-adrenergic receptor gene

Threonine allele in codon 54 of the fatty acid binding protein 2 gene does not modify the fatty acid composition of serum lipids in obese subjects

Variants in the human intestinal fatty acid binding protein 2 gene in obese subjects