
Cardiovascular Genomics (Kaikkonen lab)
Research group
Gene and cell level understanding the mechanisms driving atherosclerosis and coronary artery disease
Funder(s)
Other funders
European Research Council

Academy of Finland

Sigrid Juselius Foundation

Finnish Foundation for Cardiovascular Research

Group description
Our research group is interested in understanding how different cell types associated with coronary artery disease (CAD), namely those of the aortic wall, liver and adipose tissue contribute to disease pathogenesis. Towards this goal, we follow three lines of research (see Figure). Especially, we are interested in understanding the regulatory code that drives cell type- and disease- specific gene expression which resides in distal elements called enhancers. To identify and characterize gene regulatory processes at the level of chromatin organization and transcription, our lab has gained extensive experience in a wide range of state-of-the-art sequencing methods that some are only mastered by a limited number of labs (e.g. Hi-C, GRO-Seq and snATAC-Seq). This has allowed us to make vital contributions to the field of vascular biology and provide genome-wide annotation of non-coding RNAs that are regulated by inflammation and atherosclerosis.
Recently the field has been revolutionized by the emergence of single cell technologies and our lab has been responsible for setting up this technology at the University of Eastern Finland (10XGenomics Chromium microfluidics system). Our single cell genomics core at UEF offers consultancy and training to other research groups and is organized under the umbrella of Biocenter Finland Single Cell Omics Platform. In our own research, we use this technology to characterize cell state changes associated with the progression of atherosclerosis across disease relevant tissues in mouse models and human patient samples. Unveiling the key regulatory factors and networks driving their pathological transformation could improve early detection and provide deeper understanding of the disease process.
As the majority of the risk variants for cardiometabolic diseases are located within enhancers, we believe that understanding the genetic basis of disease requires the functional characterization of the non-coding variants in terms of allele-specific activity and target gene identification. To achieve this, my lab has recently set up massively parallel reporter assays (STARR-Seq) and CRISRP/Cas9-based screening methods and integrated as part of extensive international collaboration networks allowing access to unique patient cohorts for cell- and tissue- specific eQTL information. Ultimately, we wish to understand the relative contributions of distinct cell types in CAD and functionally characterize the genes influenced by non-coding variants.
Keywords
Group members - UEF
-
Minna Kaikkonen-Määttä Professor , Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences
-
Tiit Örd Senior Researcher , Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences
-
Maleeha Maria Postdoctoral Researcher , School of Medicine, Institute of Clinical Medicine
-
Uma Thanigai Arasu Postdoctoral Researcher , Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences
-
Nicholas Downes Early Stage Researcher , Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences
-
Mari Taipale Project Researcher , School of Medicine, Biomedicine
-
Prosanta Singha Project Researcher
-
Vanesa Tomas Bosch Early Stage Researcher
-
Ilakya Selvarajan Early Stage Researcher , Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences
-
Aarthi Ravindran Early Stage Researcher , Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences
-
Pierre Moreau Early Stage Researcher , Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences
-
Eloi Schmauch Early stage researcher, PhD candidate
-
Anu Toropainen Early Stage Researcher , Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences
-
Valtteri Nurminen Early stage researcher
-
Oscar Liu Early Stage Researcher , Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences
-
Negar Pouyanfar
-
Merja Lukkari Senior Laboratory Technician , Faculty of Health Sciences, A.I. Virtanen Institute for Molecular ...
Leader(s)
Senior Researchers
Post-doctoral Researchers
Doctoral Researchers
Technicians
Other group members
-
Huda Gilani hgilani@student.uef.fi
-
Iida Puranen ipuranen@student.uef.fi
-
Jimi Virkkala jimi.virkkala@uef.fi
Publications
-
Characterization of a functional endothelial super-enhancer that regulates ADAMTS18 and angiogenesis Mushimiyimana, I; Niskanen. H; Beter, M; Laakkonen, JP; Kaikkonen, MU; Ylä-Herttuala, S; Laham-Karam, N. 2021. Characterization of a functional endothelial super-enhancer that regulates ADAMTS18 and angiogenesis Nucleic acids research 49 14: 8078-8096. 2021
-
Genomic landscapes of non-coding RNAs regulating VEGFA and VEGFC expression in endothelial cells Mushimiyimana, Isidore; Tomas Bosch, Vanesa; Niskanen, Henri; Downes, Nicholas; Moreau, Pierre; Hartigan, Kiley; Ylä-Herttuala, Seppo; Laham-Karam, Nihay; Kaikkonen, Minna U.. 2021. Genomic landscapes of non-coding RNAs regulating VEGFA and VEGFC expression in endothelial cells Molecular and cellular biology 41 7: e00594-20. 2021
-
Integrative analysis of liver-specific non-coding regulatory SNPs associated with the risk of coronary artery disease Selvarajan, Ilakya; Toropainen, Anu; Garske, Kristina M.; López Rodríguez, Maykel; Ko, Arthur; Miao, Zong; Kaminska, Dorota; Õunap, Kadri; Örd, Tiit; Ravindran, Aarthi; Liu, Oscar H.; Moreau, Pierre R.; Jawahar Deen, Ashik; Männistö, Ville; Pan, Calvin; Levonen, Anna-Liisa; Lusis, Aldons J.; Heikkinen, Sami; Romanoski, Casey E.; Pihlajamäki, Jussi; Pajukanta, Päivi; Kaikkonen, Minna U.. 2021. Integrative analysis of liver-specific non-coding regulatory SNPs associated with the risk of coronary artery disease American journal of human genetics 108 3: 411-430. 2021
-
Meta-Analysis of Smooth Muscle Lineage Transcriptomes in Atherosclerosis and Their Relationships to In Vitro Models Conklin, Austin C.; Nishi, Hitoo; Schlamp, Florencia; Örd, Tiit; Õunap, Kadri; Kaikkonen, Minna U.; Fisher, Edward A.; Romanoski, Casey E.. 2021. Meta-Analysis of Smooth Muscle Lineage Transcriptomes in Atherosclerosis and Their Relationships to In Vitro Models Immunometabolism 3 3: e210022. 2021
-
NRF2 is a key regulator of endothelial microRNA expression under proatherogenic stimuli Linna-Kuosmanen, Suvi; Bosch, Vanesa Tomas; Moreau, Pierre R; Bouvy-Liivrand, Maria; Niskanen, Henri; Kansanen, Emilia; Kivelä, Annukka; Hartikainen, Juha; Hippeläinen, Mikko; Kokki, Hannu; Tavi, Pasi; Levonen, Anna-Liisa; Kaikkonen, Minna U. 2021. NRF2 is a key regulator of endothelial microRNA expression under proatherogenic stimuli Cardiovascular research 117 5: 1339-1357. 2021
-
Profiling of Primary and Mature miRNA Expression in Atherosclerosis Associated Cell Types Moreau, PR; Tomas Bosch, V; Bouvy-Liivrand,M; Õunap, K; Örd, T; Pulkkinen, HH; Pölönen, P; Heinäniemi, M; Ylä-Herttuala, S; Laakkonen, JP; Linna-Kuosmanen, S; Kaikkonen, MU. 2021. Profiling of Primary and Mature miRNA Expression in Atherosclerosis Associated Cell Types Arteriosclerosis, thrombosis, and vascular biology 41 7: 2149-2167. 2021
-
Single-Cell Epigenomics and Functional Fine-Mapping of Atherosclerosis GWAS Loci Örd, Tiit; Õunap, Kadri; Stolze, Lindsey; Aherrahrou, Rédouane; Nurminen, Valtteri; Selvarajan, Ilakya; Toropainen, Anu; Lönnberg, Tapio; Aavik, Einari; Yla-Herttuala, Seppo; Civelek, Mete; Romanoski, Casey E; Kaikkonen, Minna U. 2021. Single-Cell Epigenomics and Functional Fine-Mapping of Atherosclerosis GWAS Loci Circulation research 129 2: 240-258. 2021
-
Transcriptional gene regulation in endothelial cells in response to hypoxia Downes, Nicholas (toim.). 2021. Transcriptional gene regulation in endothelial cells in response to hypoxia. Itä-Suomen yliopisto. Publications of the University of Eastern Finland. Dissertations in Health Sciences 646. 2021
-
Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells Aherrahrou, Rédouane; Guo, Liang; Nagraj, Vijay Peter; Aguhob, Aaron Andrew; Hinkle, Jameson; Chen, Lisa; Soh, Joon Yuhl; Lue, Dillon; Alencar, Gabriel F; Boltjes, Arjan; van der Laan, Sander W; Farber, Emily; Fuller, Daniela; Anane-Wae, Rita; Akingbesote, Ngozi D; Manichaikul, Ani W; Ma, Lijiang; Kaikkonen, Minna U; Björkegren, Johan LM; Önengüt-Gümüscu, Suna; et al.. 2020. Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells Circulation research 127 12: 1552-1565. 2020
-
Hypoxia-Mediated Regulation of Histone Demethylases Affects Angiogenesis-Associated Functions in Endothelial Cells Hsin-Fu Liu, Oscar; Kiema, Miika; Beter, Mustafa; Ylä-Herttuala, Seppo; Laakkonen, Johanna P; Kaikkonen, Minna U. 2020. Hypoxia-Mediated Regulation of Histone Demethylases Affects Angiogenesis-Associated Functions in Endothelial Cells Arteriosclerosis thrombosis and vascular biology 40: 2665-2677. 2020