Doctoral Programme in Molecular Medicine

Program in cardiovascular diseases focuses on the pathogenesis of atherosclerosis at gene and protein levels both in vitro and in vivo with special emphasis on studies of the growth factors playing a major role in the disease progress. The program also includes projects on development of novel therapies based on gene therapy and therapeutic angiogenesis.

Research communities

Basic, Translational and Clinical Cardiovascular Medicine (CVD) 

Supervisors

• Vittorio Fortino (research group: Biomedical Informatics). Use of large-scale biomedical data, such as genetics, genomics, transcriptomics and biological knowledge bases, and data mining algorithms to build applications for biomedical research and precision medicine (e.g. biomarker and drug target discovery).
• Merja Heinäniemi (research group: Systems Genomics). Systems biology of cell-cell interactions in cardiovascular disease.
• Johanna Laakkonen (research group: Vascular biology). To define causal effects and cell-cell interactions in vascular malformations and ascending aortic aneurysm. To characterize Hippo signalling pathway in vascular diseases.
• Nihay Laham Karam. Developing regulating and targeted vectors for gene therapy. In particular, we are either using or targeting the non-coding genome to achieve this. One example is our development of lentiviral vectors using elements from super-enhancers to achieve endothelial targeted vectors to mediate angiogenesis for the treatment of ischemic diseases.
• Anna-Liisa Levonen (research group: Redox signaling). Role of Nrf2 in cancer and cardiometabolic diseases, in order to find new targets for the prevention and treatment of these diseases. Analysis of metabolic control by Nrf2 in cancer cell metabolic reprogramming, endothelial cell biology and inflammatory processes by advanced genomics, proteomics and metabolomics techniques.
• Minna Kaikkonen-Määttä (research group: Cardiovascular Genomics). Gene regulatory mechanisms underlying coronary artery disease and atherosclerosis; Genetics of cardiovascular and metabolic diseases; Analysis of gene regulation using advanced genomics techniques; Single cell sequencing
• Pasi Tavi (research group: Molecular physiology). Cellular and molecular physiology of the heart muscle cells; energy metabolism.
• Seppo Ylä-Herttuala (research group: Molecular Medicine). Pathogenesis of atherosclerosis at gene and protein level both in vitro and in vivo; development of novel therapies based on gene therapy and therapeutic angiogenesis; Virus-mediated gene delivery; Gene therapy of cardiovascular diseases

The molecular mechanisms, treatment and prevention of neurodegenerative diseases such as Alzheimer's disease, ALS, and Parkinson's disease as well as epilepsy and circulatory disorders of brain are under intensive research in this program. The research projects include projects from basic research to clinics: The risk factors, genetics and novel imaging methods of Alzheimer's disease; neuropathology of dementias; mechanisms of memory; molecular biology of the aging nervous system; the role of inflammatory factors and mitochondria in neurodegeneration; stem cell research and; the basic mechanisms and novel therapies of epilepsy.

Research communities

Neuroscience (NEURO)

Computational Modelling, Imaging and Data Science (COMMIT)

Supervisors

• Vittorio Fortino (research group: Biomedical Informatics). Use of large-scale biomedical data, such as genetics, genomics, transcriptomics and biological knowledge bases, and data mining algorithms to build applications for biomedical research and precision medicine (e.g. biomarker and drug target discovery).
• Rashid Giniatullin. Molecular pain research, experimental migraine
• Olli Gröhn (research group: Biomedical MRI). Our goal is to address fundamental neurobiological questions using modern MRI technology in combination with disease models. We use the latest existing MRI methodologies as well as develop novel (f)MRI techniques in order to understand how the brain functions and to find surrogate markers for processes associated with neurodegenerative diseases. The recent interest area has been a combination of novel fMRI techniques with brain stimulation and electrical recording in anesthetized and awake animals. Furthermore we use advanced simultaneous PET-MRI combination imaging. The search for clinically relevant, non-invasive surrogate markers for neurodegenerative processes is of ultimate importance, both for clinical patient management and for the development of specific drugs for treating these processes.
• Annakaisa Haapasalo (research group: Molecular neurodegeneration).
  Our research focus lies in the genetic background and molecular mechanisms underpinning neurodegenerative diseases, especially frontotemporal dementia (FTD). To this end, we utilize a variety of in vitro and in vivo model systems and patient-derived cells, clinical samples and data. We are especially interested in the function and dysfunction of neuronal synapses, cell metabolism, cellular degradation mechanisms, such as autophagy and proteasomes, as well as glial cells that mediate neuroinflammation.
• Mikko Hiltunen (research group: Molecular Genetics of Alzheimer's Disease). Molecular and functional genetics of Alzheimer's disease: Research Goals: To identify novel risk gene variants associated with AD and to elucidate their effects on processes relevant for pathogenesis of AD. Risk variant correlations with established biomarker levels in the brain, plasma, and cerebrospinal fluid samples of AD patients are applied; To characterize the functional role of AD-related risk genes, pathways, and co-morbidities in AD pathogenesis using in vitro and in vivo disease models. The focus in these models is set to the factors that affect early synaptic dysfunction, function of glial cells as well as ß-amyloid and tau pathology.
• Katja Kanninen (research group: Neurobiology of disease). Neurobiology of disease; cellular and molecular mechanisms of Alzheimer's disease; effects of environmental exposures on brain health.
• Sarka Lehtonen (research group: Human Brain Disease Modelling). Cellular and molecular mechanism of neurological diseases with focus on Parkinson`s disease, schizophrenia and psychopathy.
• Tarja Malm (research group: Neuroinflammation). The Neuroinflammation research group aims to form a functional fingerpring of microglia-neuron crosstalk in health and disease. We identify novel treatment strategies to modulate neuroinflammation for disease benefit. We develop novel human -based models and investigate cellular responses using various omic approaches, electrophysiology and microscopy  techniques. In addition, we take advantage of in vivo models with long-term functional outcome measures.
• Riikka Martikainen (research group: Stem cells and mitochondria). Molecular mechanisms underlying mitochondrial disease; mtDNA maintenance and defects; stem cell based models for human disease.
• Asla Pitkänen (research group: Epilepsy Research). Our goal is to (a) understand the molecular and cellular mechanisms of epileptogenesis after traumatic brain injury, (b) to develop interventions to  prevent epileptogenesis or  alleviate the disease severity.
• Juha Savinainen (research group: Endocannabinoid system as a drug target). We aim at deeper molecular level understanding on the key players orchestrating lipid signaling in health and disease, especially focusing on the endocannabinoid system. We utilize activity-based protein profiling and metabolomics in exploring serine hydrolase activity in different in vitro and in vivo models. Our current efforts focus specifically on the mechanisms of migraine and other pain conditions.
• Alejandra Sierra Lopez (research group: Multiscale imaging). The multiscale imaging group is a multidisciplinary team interested in the application, combination and development of imaging modalities focused in brain at several scales. Our greatest interest is the study of the structure of the healthy and diseased brain from the macro- and microscale with non-invasive techniques to the nanoscale with microscopy techniques in combination with image processing, data analyses and tissue modelling.
• Heikki Tanila (research group: Neurobiology of Memory). Neurobiological mechanisms of memory and memory disorders.
• Jussi Tohka research group: Biomedical Image Analysis). Biomedical image analysis; Machine learning; Neuroinformatics

Program focuses on the genetic background and interaction of genetic and dietary factors in etiology of type 2 diabetes, metabolic syndrome and obesity. The influence of nutrition factors on the gene expression in adipose tissue and white blood cells is studied in order to find out the regulation of type 2 diabetes, obesity and cholesterol metabolism.

Research communities 

Metabolic diseases

Supervisors

• Sami Heikkinen (research group: Genetics and gene regulation in metabolic diseases). Genetics and gene regulation in metabolic diseases
• Vanessa de Mello Laaksonen (research group: Nutrigenomics). Molecular role of novel protective metabolites (T2DM) in human and cell culture studies.
• Jussi Pihlajamäki. Metabolic consequences of obesity and related diseases, especially fatty liver disease

Stem cell research program includes projects studying the differentiation of human embryonic stem cells to brain cells and cardiac muscle cells, differentiation of mouse embryonic brain stem cells to neurons, and the differentiation and transfer of both human and mouse hematopoietic stem cells in disease models of neurodegenerative and cardiovascular diseases. Modification of stem cells with gene transfers, use of stem cells as tools of gene therapy, studies on combining gene and cell therapy with conventional pharmacotherapy, and imaging of the stem cells are among the most important parts of the program.

Supervisors

• Sarka Lehtonen (research group: Human Brain Disease Modelling). Stem cell based models for neurological diseases and drug discoveries (2D, 3D and organoids), Blood-brain barrier on chip .
• Riikka Martikainen (research group: Stem cells and mitochondria). Stem cell based models for human disease.
• Pasi Tavi (research group: Molecular physiology). Stem cell based cell and tissue models; Bioengineering.
• Seppo Ylä-Herttuala (research group: Molecular Medicine). Pathogenesis of atherosclerosis; Development of novel therapies based on gene therapy and therapeutic angiogenesis using stem cells

Acute pancreatitis: Deficiency of polyamines due to increased polyamine catabolism is related to the pathogenesis of severe acute pancreatitis in transgenic mice and rats. The program focuses on clarifying the molecular mechanisms of the early phases of pancreatitis, and also on the use of polyamine analogues in regeneration of lethal lesions of the pancreas and some other organs.

Regulation of the immune system: Special interests include the CD40-mediated influences on the cells of the immune system, and CD40-regulated inflammation reaction mediated by endothelial cells.

Nuclear receptors and transcriptional control of gene expression: The main focus is on steroid hormone regulated gene activity in cancer and inflammatory cells.

Supervisors

• Carsten Carlberg (research group: Epigenomics of vitamin D). Epigenomics of vitamin D: transcriptomic (RNA-seq) and epigenomic (ATAC-seq and ChPmentation) studies in human monocytic leukemia cells (THP-1) and PBMCs isolated from healthy human donors as well from vitamin D intervention studies
• Tuure Kinnunen (research group: Immunology of type 1 diabetes). Immunology of type 1 diabetes.
• Sarka Lehtonen (research group: Human Brain Disease Modelling). Pathological crosstalk between microglia and astrocytes in Parkinson`s disease
• Einari Niskanen (research group: Regulatory mechanisms of steroid receptors). We aim to understand mechanisms of transcription regulation and transcription factor crosstalk. Our main model systems are glucocorticoid receptor, which we study in context of inflammatory signaling, and androgen receptor, which we study in context of prostate cancer. We use genome-wide techniques (ChIP-seq, RNA-seq, GRO-seq, PRO-seq), latest proteomics tools (ChIP-SICAP, BioID) and various bioinformatics approaches to understand mechanisms of transcription regulation in mammalian cells.
• Ville Paakinaho (research group: Pioneer factor and steroid receptor biology in disease). Principals of glucocorticoid receptor biology; genomics (ChIP-seq, ATAC-seq), transcriptomics (RNA-seq), oligomerization

Translational cancer research program includes projects on molecular mechanisms, genomics and quantitative imaging features of cancer. A special emphasis is on understanding development of cancer as well as formation of cancer drug resistance. The program also includes projects to develop novel cancer drugs and diagnostic tools. Close collaboration between University of Eastern Finland and Kuopio University Hospital catchment area joins forces of clinical and basic researchers to fight cancer, bringing clinical understanding of the diagnostics and treatment, with the goal to bring personalized medicine to the clinic.

Research communities

Multidisciplinary Cancer Research (CANCER) 

Supervisors

• Vittorio Fortino (research group: Biomedical Informatics). Use of large-scale biomedical data, such as genetics, genomics, transcriptomics and biological knowledge bases, and data mining algorithms to build applications for biomedical research and precision medicine (e.g. biomarker and drug target discovery).
• Merja Heinäniemi (research group: Systems Genomics). Our goal is to elucidate disease mechanisms that are related to aberrant regulation of cell states. We develop computational models based on systems biology and data analysis tools with bioinformatics and machine learning methods suitable for integrating different types of genomics data or combining datasets across studies. We apply them in our own research that utilizes large omics datasets and collect new genomics data from cell models and human studies to unravel the complexity of hematological and lymphoid malignancies.
• Tiina Jääskeläinen. Steroid receptor-coregulator hubs regulating chromatin protein and gene networks in treatment resistant cancer cells: Mechanisms of resistance to hormonal therapies in prostate cancer and leukemia cell models using integrated genome- and proteome-wide approaches.
• Kirsi Ketola (research group: Cancer Cell Plasticity). Cancer cell plasticity, treatment resistance and neuroendocrine differentiation in prostate cancer.
• Leena Latonen (research group: Cancer stress biology). Molecular and tissue biology of prostate cancer; role of cellular stress response pathways in cancer drug resistance
• Anna-Liisa Levonen (research group: Redox signaling). Role of Nrf2 in cancer and cardiometabolic diseases, in order to find new targets for the prevention and treatment of these diseases. Analysis of metabolic control by Nrf2 in cancer cell metabolic reprogramming, endothelial cell biology and inflammatory processes by advanced genomics, proteomics and metabolomics techniques.
• Einari Niskanen (research group: Regulatory mechanisms of steroid receptors). We aim to understand mechanisms of transcription regulation and transcription factor crosstalk. Our main model systems are glucocorticoid receptor, which we study in context of inflammatory signaling, and androgen receptor, which we study in context of prostate cancer. We use genome-wide techniques (ChIP-seq, RNA-seq, GRO-seq, PRO-seq), latest proteomics tools (ChIP-SICAP, BioID) and various bioinformatics approaches to understand mechanisms of transcription regulation in mammalian cells.
• Ville Paakinaho (research group: Pioneer factor and steroid receptor biology in disease). Steroid receptor and pioneer factor signaling in cancer cells; genomics (ChIP-seq, ATAC-seq), transcriptomics (RNA-seq, GRO-seq), single-cell genomics, single-molecule imaging.
• Jorma Palvimo (research group: Steroid Receptors and SUMO Modifications in the Regulation of Gene Networks and Cellular Plasticity). Steroid receptor-coregulator hubs regulating chromatin protein and gene networks in treatment resistant cancer cells: Mechanisms of resistance to hormonal therapies in prostate cancer and leukemia cell models using integrated genome- and proteome-wide approaches.
• Sanna Pasonen-Seppänen (research group: Tumor-stroma interaction). The molecular mechanisms of tumor-stroma interaction in melanoma. We are studying the interaction of tumor and immune cells and the molecular mechanisms of pro-tumor inflammation, and how extracellular matrix molecule hyaluronan is involved in these.
• Kirsi Rilla (research group: Rilla group). Extracellular vesicles as systemic messengers