Cell Division and Cytoskeleton
Current work in the Cell Division and Cytoskeleton group is focused on investigation of molecular mechanisms of chromosomal and cytoskeletal dynamics, whose alterations during the cell cycle promote aneuploidy and metastasis, and consequently facilitate tumorigenesis.
Our Research
Microtubules are key components of the cytoskeleton, enabling intracellular transport and contributing to essential cellular processes such as cell division and migration. They are also important drug targets in cancer therapy, particularly for anticancer agents like vinca alkaloids and taxanes. However, these drugs often face clinical challenges, including side effects like neuropathy and neurotoxicity, and the development of drug resistance. This has led to growing interest in targeting other molecules or molecular properties related to microtubule functions, such as tubulin post-translational modifications (PTMs) and tubulin isotypes, collectively known as the "tubulin code."
Cell Division
Tubulin detyrosination is one of these PTMs that is frequently altered in cancers and is linked to tumor aggressiveness and poor patient prognosis, making it a promising molecular target. Moreover, many motor proteins that interact with tubulin are deregulated in cancer, and inhibitors targeting these proteins are undergoing clinical trials. Given the impact of tubulin PTMs on modulating motor protein activity and their association with cancer, this underexplored area holds significant potential for the development of novel anticancer therapies.
Our research focuses on:
- Mechanisms of chromosome congression and segregation during mitosis
- Regulation of microtubule dynamics
- The impact of tubulin PTMs on motor proteins and their roles in chromosomal and cellular movements
Eibes S, Rajendraprasad G, Guasch-Boldu C, Kubat M, Steblyanko Y, Barisic M: CENP-E activation by Aurora A and B controls kinetochore fibrous corona disassembly. Nat Commun 2023;1;14(1):5317
Lavrsen K, Rajendraprasad G, Leda M, Eibes S, Vitiello E, Katopodis V, Goryachev AB, Barisic M: Microtubule detyrosination drives symmetry breaking to polarize cells for directed cell migration. PNAS 2023;120(22):e2300322120
Steblyanko Y, Rajendraprasad G, Osswald M, Eibes S, Jacome A, Geley S, Pereira AJ, Maiato H, Barisic M: Microtubule poleward flux in human cells is driven by the coordinated action of four kinesins. EMBO J 2020;e105432
Liao S, Rajendraprasad G, Wang N, Eibes S, Gao J, Yu H, Wu G, Tu X, Huang H, Barisic M, Xu C: Molecular basis of vasohibins-mediated detyrosination and its impact on spindle function and mitosis. Cell Res 2019;29(7):533-547
Barisic M, Silva e Sousa R, Tripathy SK, Magiera MM, Zaytsev AV, Pereira AL, Janke C, Grishchuk EL, Maiato H: Microtubule detyrosination guides chromosomes during mitosis. Science 2015;348(6236):799-803
Barisic M, Aguiar P, Geley S, Maiato H: Kinetochore motors drive congression of peripheral polar chromosomes by overcoming random arm-ejection forces. Nat Cell Biol 2014;16(12):1249-1256
Barisic M, Sohm B, Mikolcevic P, Wandke C, Rauch V, Ringer T, Hess M, Bonn G, Geley S: Spindly/CCDC99 is required for efficient chromosome congression and mitotic checkpoint regulation. Mol Biol Cell 2010;21(12):1968-1981
Group Leader: Marin Barisic
Marin Barisic earned his Diploma in Molecular Biology at the University of Zagreb in Croatia, and his PhD in Molecular Cell Biology and Oncology at the Innsbruck Medical University in Austria. After finishing his Postdoc at the Institute for Molecular and Cell Biology in Porto, Portugal, he started his own research group as a Group Leader in the Cell Division and Cytoskeleton lab at the Danish Cancer Institute (DCI) in Copenhagen, Denmark.
Work in the Cell Division & Cytoskeleton lab is based on investigation of molecular mechanisms behind chromosomal and cytoskeletal dynamics - the processes whose aberrations during the cell cycle often facilitate tumorigenesis.
ORCID: 0000-0001-7587-3867
Key Funding
Lundbeck Foundation
Novo Nordisk Foundation
Independent Research Fund Denmark