A5027482380- Pluripotent Stem Cells Research
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neural Engineering
- 3D Printing in Biomedical Research
- Lipoproteins and Cardiovascular Health
- Cell Image Analysis Techniques
- Cardiomyopathy and Myosin Studies
- Tissue Engineering and Regenerative Medicine
- Ion channel regulation and function
- Cancer, Lipids, and Metabolism
- CRISPR and Genetic Engineering
- Diabetes, Cardiovascular Risks, and Lipoproteins
- ECG Monitoring and Analysis
- Genetics, Bioinformatics, and Biomedical Research
- Genetic Associations and Epidemiology
- Congenital heart defects research
- Receptor Mechanisms and Signaling
- Cardiac pacing and defibrillation studies
- Cholesterol and Lipid Metabolism
- Cardiovascular Function and Risk Factors
- Lipid metabolism and disorders
- Electrospun Nanofibers in Biomedical Applications
- RNA Research and Splicing
- Nutrition, Genetics, and Disease
- Cardiovascular Effects of Exercise
Tampere University
2016-2025
Tampere University Hospital
2015-2024
Pirkanmaa Hospital District
2022
FIT Biotech (Finland)
2012-2017
Tampere University of Applied Sciences
2006-2017
King's College London
2016
Hospital General Universitario Gregorio Marañón
2016
University College Hospital at Westmoreland Street
2015
University College London
2015
Gladstone Institutes
2009-2014
Abstract Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These survived the founding bottleneck rather than being distributed over large ultrarare variants. Although this effect is well established Mendelian genetics, its value common disease genetics less explored 1,2 . FinnGen aims to study genome and national health register data...
Hypertriglyceridemia is common in the general population, but its mechanism largely unknown. In previous work human apo CIII transgenic (HuCIIITg) mice were found to have elevated triglyceride levels. this report, for hypertriglyceridemia was studied. Two different HuCIIITg mouse lines used: a low expressor line with serum triglycerides of approximately 280 mg/dl, and high 1,000 mg/dl. Elevated mainly VLDL. VLDL particles 1.5 times more triglyceride-rich than controls. The total amount...
ABSTRACT Population isolates such as Finland provide benefits in genetic studies because the allelic spectrum of damaging alleles any gene is often concentrated on a small number low-frequency variants (0.1% ≤ minor allele frequency < 5%), which survived founding bottleneck, opposed to being distributed over much larger ultra--rare variants. While this advantage well-- established Mendelian genetics, its value common disease genetics has been less explored. FinnGen aims study genome and...
Long QT syndrome (LQTS) is caused by functional alterations in cardiac ion channels and associated with prolonged repolarization time increased risk of ventricular arrhythmias. Inherited type 2 LQTS (LQT2) drug-induced both result from altered function the hERG channel. We investigated whether electrophysiological characteristics LQT2 can be recapitulated vitro using induced pluripotent stem cell (iPSC) technology. Spontaneously beating cardiomyocytes were differentiated two iPSC lines...
Lipoprotein lipase (LPL)-deficient mice have been created by gene targeting in embryonic stem cells. At birth, homozygous knockout pups threefold higher triglycerides and sevenfold VLDL cholesterol levels than controls. When permitted to suckle, LPL-deficient become pale, then cyanotic, finally die at approximately 18 h of age. Before death, triglyceride are severely elevated (15,087 +/- 3,805 vs 188 71 mg/dl controls). Capillaries tissues engorged with chylomicrons. This is especially...
Arterial smooth muscle cell (SMC) migration and proliferation are central features in atherogenesis. Altered gene expression atherosclerotic lesions have some similar characteristics with certain solid tumors thus might mechanisms that lead to SMC proliferation. Among cancer cells common genome-wide hypomethylation which correlates transformation tumor progression, coincident over-expression of methyltransferase (MTase). The purpose the present study was analyze whether alterations DNA...
The low‐molecular‐mass insulin‐like growth factor‐binding protein (IGF‐BP) and placental 12 (PP12) are identical proteins that present in human serum, amniotic fluid, secretory endometrium decidua. IGF‐BP/PP12 is believed to act as an autocrine or paracrine regulator of cell growth. A cDNA clone encompassing the entire coding region this was isolated from a decidual library. authenticity verified by vitro transcription/translation experiments identity 10 N‐terminal amino acids deduced for...
Background The growth of stem cells in vitro conditions requires optimal balance between signals mediating cell survival, proliferation, and self-renewal. For clinical application cells, the use completely defined elimination all animal-derived materials from establishment, culture, differentiation processes is desirable. Methodology/Principal Findings Here, we report development a fully xeno-free medium (RegES), capable supporting expansion human embryonic (hESC), induced pluripotent (iPSC)...
Induced pluripotent stem cells (iPSC) provide means to study the pathophysiology of genetic disorders. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a malignant inherited ion channel disorder predominantly caused by mutations in cardiac ryanodine receptor (RyR2). In this cellular characteristics CPVT are investigated and whether electrophysiological features mutation can be mimicked using iPSC -derived cardiomyocytes (CM).Spontaneously beating CMs were differentiated from...
The ability of human pluripotent stem cells to differentiate towards the cardiac lineage has attracted significant interest, initially with a strong focus on regenerative medicine. ultimate goal repair heart by cardiomyocyte replacement has, however, proven challenging. Human differentiation been difficult control, but methods are improving, and process, certain extent, can be manipulated directed. cell-derived cardiomyocytes described date exhibit rather immature functional structural...
Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected are various, influences of cellular calcium cycling on LQTS events unknown. To better understand arrhythmias, we performed current-clamp intracellular ([Ca(2+)]i) measurements cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs [Ca(2+)]i transients were prolonged in...
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly malignant inherited arrhythmogenic disorder. Type 1 CPVT (CPVT1) caused by cardiac ryanodine receptor (RyR2) gene mutations resulting in abnormal calcium release from sarcoplasmic reticulum. Dantrolene, an inhibitor of Ca2+ release, has been shown to rescue this vitro. We assessed the antiarrhythmic efficacy dantrolene six patients carrying various RyR2 causing CPVT. The underwent exercise stress test before and after...
Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms interactions environmental triggers in multi-ethnic sample 6,073 cases 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 DPB1*04:02) discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant at TRA DQB1*06:02 loci...
PURPOSE Family history (FH) and pathogenic variants (PVs) are used for guiding risk surveillance in selected high-risk women but little is known about their impact breast cancer screening on population level. In addition, polygenic scores (PRSs) have been shown to efficiently stratify through combining information common genetic factors into one measure. METHODS longitudinal real-life data, we evaluate PRS, FH, PVs stratified screening. Using FinnGen (N = 117,252), linked the Mass Screening...
The recent development of human induced pluripotent stem (iPS) cells [1–5] has reshaped the scientific and political landscape cell biology. iPS provide an unprecedented opportunity to study pathophysiology diseases, understand biology, identify new therapeutic targets, test therapies. Furthermore, they offer possibility transplanting that are genetically identical their recipient. iPS not included in heated debates over ethics embryonic research because embryos or oocytes used....
The functionality of a cardiomyocyte is primarily measured by analyzing the electrophysiological properties cell. analysis beating behavior single cardiomyocytes, especially ones derived from stem cells, challenging but well warranted. In this study, video-based method that non-invasive and label-free introduced applied for study human cardiomyocytes induced pluripotent cells. dissociated cell-derived was visualized with microscope motion video-recorded. Minimum quadratic difference, digital...
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease, which affects the structure of heart muscle tissue. The clinical symptoms include arrhythmias, progressive failure, and even sudden death but mutation carrier can also be totally asymptomatic. To date, over 1400 mutations have been linked to HCM, mostly in genes encoding for sarcomeric proteins. However, pathophysiological mechanisms disease are still largely unknown. Two founder HCM Finland located myosin‐binding protein C (...
To promote the transition of cell cultures from 2D to 3D, hydrogels are needed biomimic extracellular matrix (ECM). One potential material for this purpose is gellan gum (GG), a biocompatible and mechanically tunable hydrogel. However, GG alone does not provide attachment sites cells thrive in 3D. option biofunctionalization introduction gelatin, derivative abundant ECM protein collagen. Unfortunately, gelatin lacks cross-linking moieties, making production self-standing difficult under...
The growing importance of human induced pluripotent stem cell-derived cardiomyoyctes (hiPSC-CMs), as patient-specific and disease-specific models for studying cellular cardiac electrophysiology or preliminary cardiotoxicity tests, generated better understanding hiPSC-CM biophysical mechanisms great amount action potential calcium transient data. In this paper, we propose a new in silico model, with particular attention to Ca2+ handling. We used i) the Paci2013 model starting point, ii)...
Dilated cardiomyopathy (DCM) is one of the leading causes heart failure and transplantation. A portion familial DCM due to mutations in LMNA gene encoding nuclear lamina proteins lamin C without adequate treatment these patients have a poor prognosis. To get better insights into pathobiology behind this disease, we focused on modeling LMNA-related using human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM). Primary skin fibroblasts from carrying most prevalent Finnish founder...