Our research is focused on understanding the effects of cardiometabolic diseases, muscle wasting 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, especially in the heart and skeletal muscles, 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
Luis Gand, postdoc
Alfredo Ortega-Alonso, postdoc
Liina Uusitalo-Kylmälä, postdoc
Aino Männistö, PhD student
Erik Niemi, PhD student
Emilia Oksaranta, PhD student
Kialiina Tonttila, PhD student
Leevi Kahri, MSc student
Niko Pennanen, MSc student
Gizaw NY, Kolari K, Kallio P, Alitalo K, Kivelä R. Inhibiting cholesterol synthesis halts rhabdomyosarcoma growth via ER stress and cell cycle arrest. EMBO Mol Med. 2025 Dec;17(12):3586-3606. doi: 10.1038/s44321-025-00336-x
Männistö A, Tonttila K, Ortega-Alonso A, Nurmi H, Uusitalo-Kylmälä L, Amudhala Hemanthakumar K, Saikkala E, Myllykangas S, Vertainen S, Nissinen TA, Pasternack A, Ritvos O, Alitalo KK, Hulmi JJ, Kivelä R. Combined angiogenic and hypertrophic gene therapy enhances skeletal muscle growth. Am J Physiol Cell Physiol. 2025 Aug 1;329(2):C540-C559. doi: 10.1152/ajpcell.00966.2024
Mäntyselkä S, Ahvenlammi M, Vartiainen J, Halonen EJ, Kolari K, Wackerhage H, Permi P, Varjosalo M, Kelahaara MM, Ahtiainen JP, Kalenius E, Kivelä R, Hulmi JJ. Glycolytic metabolism and biomass production from glucose in human skeletal muscle growth. Am J Physiol Cell Physiol. 2025 Nov 1;329(5):C1560-C1576. doi: 10.1152/ajpcell.00525.2025
Karaman S, Lehti S, Zhang C, Taskinen MR, Käkelä R, Mardinoglu A, Brorson H, Alitalo K, Kivelä R. Multi-omics characterization of lymphedema-induced adipose tissue resulting from breast cancer-related surgery. FASEB J. 2024 Oct 31;38(20):e70097. doi: 10.1096/fj.202400498RR
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. Contribution of VEGF-B-Induced Endocardial Endothelial Cell Lineage in Physiological Versus Pathological Cardiac Hypertrophy. Circ Res. 2024 May 24;134(11):1465-1482. doi: 10.1161/CIRCRESAHA.123.324136
Mäntyselkä S, Kolari K, Baumert P, Ylä-Outinen L, Kuikka L, Lahtonen S, Permi P, Wackerhage H, Kalenius E, Kivelä R, Hulmi JJ. Serine synthesis pathway enzyme PHGDH is critical for muscle cell biomass, anabolic metabolism, and mTORC1 signaling. Am J Physiol Endocrinol Metab. 2024 Jan 1;326(1):E73-E91. doi: 10.1152/ajpendo.00151.2023
Gizaw NY, Kallio P, Punger T, Gucciardo E, Haglund C, Böhling T, Lehti K, Sampo M, Alitalo K, Kivelä R. PROX1 transcription factor controls rhabdomyosarcoma growth, stemness, myogenic properties and therapeutic targets. Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2116220119. doi: 10.1073/pnas.2116220119
Hemanthakumar KA, Fang S, Anisimov A, Mäyränpää MI, Mervaala E, Kivelä R. Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells. Elife. 2021 Mar 4;10:e62678. doi: 10.7554/eLife.62678
Räsänen M, Sultan I, Paech J, Hemanthakumar KA, Yu W, He L, Tang J, Sun Y, Hlushchuk R, Huan X, Armstrong E, Khoma OZ, Mervaala E, Djonov V, Betsholtz C, Zhou B, Kivelä R, Alitalo K. VEGF-B Promotes Endocardium-Derived Coronary Vessel Development and Cardiac Regeneration. Circulation. 2021 Jan 5;143(1):65-77. doi: 10.1161/CIRCULATIONAHA.120.050635
Helle E, Ampuja M, Dainis A, Antola L, Temmes E, Tolvanen E, Mervaala E, Kivelä R. HiPS-Endothelial Cells Acquire Cardiac Endothelial Phenotype in Co-culture With hiPS-Cardiomyocytes. Front Cell Dev Biol. 2021 Aug 6;9:715093. doi: 10.3389/fcell.2021.715093
Kivelä R, Hemanthakumar KA, Vaparanta K, Robciuc M, Izumiya Y, Kidoya H, Takakura N, Peng X, Sawyer DB, Elenius K, Walsh K, Alitalo K. Endothelial Cells Regulate Physiological Cardiomyocyte Growth via VEGFR2-Mediated Paracrine Signaling. Circulation. 2019 May 28;139(22):2570-2584. doi: 10.1161/CIRCULATIONAHA.118.036099
Talman V, Kivelä R. Cardiomyocyte-Endothelial Cell Interactions in Cardiac Remodeling and Regeneration. Front Cardiovasc Med. 2018 Jul 26;5:101. doi: 10.3389/fcvm.2018.00101
Hulmi JJ, Nissinen TA, Räsänen M, Degerman J, Lautaoja JH, Hemanthakumar KA, Backman JT, Ritvos O, Silvennoinen M, Kivelä R. Prevention of chemotherapy-induced cachexia by ACVR2B ligand blocking has different effects on heart and skeletal muscle. J Cachexia Sarcopenia Muscle. 2018 Apr;9(2):417-432. doi: 10.1002/jcsm.12265
Kivelä R, Salmela I, Nguyen YH, Petrova TV, Koistinen HA, Wiener Z, Alitalo K. The transcription factor Prox1 is essential for satellite cell differentiation and muscle fibre-type regulation. Nat Commun. 2016 Oct 12;7:13124. doi: 10.1038/ncomms13124
