Our research is focused on understanding the effects of cardiometabolic diseases and physical activity on vasculature, endothelial cells and tissue physiology. Our aim is to identify mechanisms mediating the health benefits of exercise and to discover novel treatment options for cardiometabolic diseases. Our group also studies skeletal muscle growth and muscle wasting, and the pediatric cancer rhabdomyosarcoma.
Cardiometabolic diseases, such as cardiovascular disease, type 2 diabetes and hypertension, are the number one cause of death in the western world; thus they present an urgent need for novel therapies. Despite recent progress in the treatment options for cardiometabolic diseases, the clinical prognosis of e.g. heart failure is currently worse than prognosis of most cancers. Blood vessels are essential in all tissues for the delivery of oxygen and nutrients. Recent studies have demonstrated that blood vessels are much more than an inert conduit for blood flow. Instead, endothelial cells lining the vessels are active regulators of tissue growth, metabolism and regeneration.
We want to understand how the interaction between endothelial cells and other cell types in the tissues is regulated and how the intercellular communication is disturbed in cardiometabolic disease. The goal of our studies is to enhance understanding on the role of vasculature in cardiometabolic disease and in mediating the health benefits of exercise. Eventually, we aim to identify novel therapeutic targets for cardiometabolic disease and muscle wasting.
We are also interested in skeletal muscle stem cell differentiation and skeletal muscle physiology and pathology, with a special focus on the role of the PROX1 transcription factor. Our aim is to understand the role and function of PROX1 in skeletal muscle physiology and in rhabdomyosarcoma, which is a highly malignant pediatric cancer with myogenic features.
Current Group members
Liina Uusitalo-Kylmälä, Postdoctoral researcher
Alfredo Ortega-Alonso, Postdoctoral researcher
Minna Ampuja, Postdoctoral researcher
Kalle Kolari, Postdoctoral researcher
Nebeyu Gizaw Yosef, PhD student
Aino Männistö, PhD student
Kialiina Tonttila, PhD student
Erik Niemi, PhD student
Emilia Oksaranta, PhD student
Venla Hakkarainen, MSc student
Emmi Helle, Postdoctoral researcher/Clinical research fellow
Oiva Arvola, Postdoctoral researcher
Karthik Amudhala Hemanthakumar, PhD student
Ilse Paetau, Lab manager
Outi Hasu, MSc student
Erik Saikkala, MSc student
Jacob Andersson, Medical student
Sami Myllykangas, Medical student
Siiri Toropainen, MSc student
Laura Antola, MSc student
Tatjana Punger, MSc student
Elviira Hyvönen, Medical student
Charlotte Gouret, Undergraduate student
Maxime Laird, Undergraduate student
Manon Gruchet, Undergraduate student
Kirsi Mattinen, Laboratory technician
Multi-omics characterization of lymphedema-induced adipose tissue resulting from breast cancer-related surgery. Karaman S, Lehti S, Zhang C, Taskinen MR, Käkelä R, Mardinoglu A, Brorson H, Alitalo K, Kivelä R. FASEB Journal, 38(20):e70097, 2024
Contribution of VEGF-B-Induced Endocardial Endothelial Cell Lineage in Physiological Versus Pathological Cardiac Hypertrophy. Sultan I, Ramste M, Peletier P, Hemanthakumar KA, Ramanujam D, Tirronen A, von Wright Y, Antila S, Saharinen P, Eklund L, Mervaala E, Ylä-Herttuala S, Engelhardt S, Kivelä R, Alitalo K. Circulation Research 134(11):1465-1482, 2024.
Serine synthesis pathway enzyme PHGDH is critical for muscle cell biomass, anabolic metabolism, and mTORC1 signaling. Mäntyselkä S, Kolari K, Baumert P, Ylä-Outinen L, Kuikka L, Lahtonen S, Permi P, Wackerhage H, Kalenius E, Kivelä R, Hulmi JJ. American Journal of Physiology – Endocrinology and Metabolism, 326(1):E73-E91, 2023.
PROX1 transcription factor controls rhabdomyosarcoma growth, stemness, myogenic properties and therapeutic targets. Gizaw NY, Kallio P, Punger T, Gucciardo E, Haglund C, Böhling T, Lehti K, Sampo M, Alitalo K, Kivelä R. 2022, Proc Nat Acad Sci, 119(49):e2116220119.
Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells. Hemanthakumar KA, Fang S, Anisimov A, Mäyränpää MI, Mervaala E, Kivelä R.2021, Elife 10:e62678.
VEGF-B promotes endocardium-derived coronary vessel development and cardiac regeneration. Räsänen M, Sultan I, Paech J, Hemanthakumar KA, Yu W, He L, Tang J, Sun Y, Hlushchuk R, HuanX, Armstrong E, Khoma OZ, Mervaala E, Djonov V, Betsholtz C, Zhou B, Kivelä R, Alitalo K. 2021, Circulation, 143: 65-77.
Flow-Induced Transcriptomic Remodeling of Endothelial Cells Derived From Human Induced Pluripotent Stem Cells. Helle E, Ampuja M, Antola L, Kivelä R. 2020, Front Physiol, 11:591450.
Angiogenesis and angiocrines regulating heart growth. Hemanthakumar KA, Kivelä R. 2020, Vasc Biol. 2(1): R93-R104.
Endothelial Cells Regulate Physiological Cardiomyocyte Growth via VEGFR2 -Mediated Paracrine Signaling. Kivelä R, Hemanthakumar KA, Vaparanta K, Robciuc M, Izumiya Y, Kidoya H, Takakura N, Peng X, Sawyer DB, Elenius K, Walsh K, Alitalo K. 2019, Circulation, 139:2570-2584.
Cardiomyocyte—Endothelial Cell Interactions in Cardiac Remodeling and Regeneration. Talman V, Kivelä R. 2018, Front Cardiovasc Med, 5:101.
Prevention of chemotherapy-induced cachexia by ACVR2B ligand blocking has different effects on heart and skeletal muscle. Hulmi JJ, Nissinen TA, Räsänen M, Degerman J, Lautaoja JH, Hemanthakumar KA, Backman JT, Ritvos O, Silvennoinen M, Kivelä R. 2018, J Cachexia, Sarcopenia, Muscle, 9:417-432.
The transcription factor Prox1 is essential for satellite cell differentiation and muscle fibre type regulation. Kivelä R, Salmela I, Nguyen YH, Petrova TV, Koistinen HA, Wiener Z, Alitalo K. 2016, Nat Commun, 7: 13124.
