ZFIN ID: ZDB-PERS-200824-1
Kojic, Snezana
Email: snezanakojic@imgge.bg.ac.rs
Affiliation: Laboratory for Molecular Biology, IMGGE
Address: Group for Muscle Cellular and Molecular Biology, Laboratory for Molecular Biology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade Vojvode Stepe 444a, 11042 Belgrade 152
Phone: +381113976658;
ORCID ID: 0000-0001-5090-1278

Group for Muscle Cellular and Molecular Biology investigates different aspects of striated muscle structure and function. Our interest is in molecular mechanisms of heart regeneration, skeletal muscle repair and adaptation of muscle cells to stress. Our research focus is on ANKRD1 and ANKRD2 genes and their roles in these processes.

Our engagement in the field of zebrafish research has been recently acknowledged and awarded by the grant of Serbian Science Fund in a very competitive call (105 out of 917 granted projects).

Project title: Zebrafish ankrd1a as a common player in heart regeneration and skeletal muscle repair - a new prospect for unlocking regenerative potential of human heart - ZEBARR
PI: Snezana Kojic
This research is supported by the SCIENCE FUND of the Republic of Serbia, Grant No 7739807
Project duration 01.01.2022.-31.12.2024.
Project budget 436,543.45 Euro


Heart diseases, and particularly myocardial infarction (MI), are the leading cause of death worldwide due to incapability of the injured human heart to regenerate. In contrast to humans, zebrafish has remarkable ability to regenerate injured heart, while both humans and zebrafish efficiently repair the wounded skeletal muscle. This implies that the key for unlocking endogenous regenerative potential of human heart may be hidden in regeneration-competent skeletal muscle. The ZEBARR project offers novel approach to identify targets that might contribute to restoration of impaired cardiac function by promotion of myocardial regeneration. Since prerequisite for any innovation is to gain a critical mass of fundamental knowledge, ZEBARR ambition is to expand the understanding of cellular and molecular mechanisms involved in heart regeneration and skeletal muscle repair. Based on our preliminary results we select ankrd1a gene, activated in healing of both zebrafish heart and skeletal muscle, as a promising candidate to investigate using novel ZEBARR concept. Function of zebrafish ankrd1a and identification of its downstream targets and associated pathways will be determined in cryoinjured heart and mechanically injured skeletal muscle of ankrd1a mutant. We propose to monitor outcomes of molecular and cellular processes contributing to the heart regeneration and skeletal muscle repair by immunohistochemistry and fluorescent microscopy, analysis of gene expression and transcriptome profiling. Moreover, we aim at addressing the possibility that ankrd1a mediate beneficial effect of exercise on muscle regeneration and repair, further contributing to healing process. We believe the ANKRD1 is an attractive target for translational studies to impact the field of regenerative biology and contribute to efforts directed towards the development of efficient therapies to push human heart to become prone to regeneration.

Using a TgBAC(ankrd1a:EGFP) reporter line, we showed that activation of ankrd1a in cryoinjured heart is restricted to border zone cardiomyocytes, implicating this gene in dedifferentiation, proliferation and migration of cardiomyocytes involved in regeneration. After stab wound injury of skeletal muscle expression of the fluorescent reporter was observed from 3 dpi, when new EGFP-positive muscle cells emerged inside the injury zone. At later time points, EGFP-positive myofibers were visible in the deeper tissue layers, concomitant with active repair of the injured tissue. In cryoinjured skeletal muscle, strong activation of ankrd1a was also observed in myofibers adjacent to the injury, and in those on uninjured side. Detection of the transgene in both newly formed myofibers that invade the wound and in the apparently uninjured tissue surrounding the injury suggests the role of ankrd1a in skeletal muscle tissue repair and adaptive processes in uninjured myofibers surrounding the injury site. Our results implicate ankrd1a in zebrafish muscle regeneration, repair and remodelling, promoting it as an attractive target for translational studies, as a player in muscle healing and as a sensor of stressed muscle.

Milosevic, E., Stanisavljevic, N., Boskovic, S., Stamenkovic, N., Novkovic, M., Bavelloni, A., Cenni, V., Kojic, S., Jasnic, J. (2023) Antitumor activity of natural pigment violacein against osteosarcoma and rhabdomyosarcoma cell lines. Journal of Cancer Research and Clinical Oncology. 149(13):10975-10987
Boskovic, S., Marin Juez, R., Stamenkovic, N., Radojkovic, D., Yr Stainier, D., Kojic, S. (2021) The stress responsive gene ankrd1a is dynamically regulated during skeletal muscle development and upregulated following cardiac injury in border zone cardiomyocytes in adult zebrafish. Gene. 792:145725
Boskovic, S., MarĂ­n-Juez, R., Jasnic, J., Reischauer, S., El Sammak, H., Kojic, A., Faulkner, G., Radojkovic, D., Stainier, D.Y.R., Kojic, S. (2018) Characterization of zebrafish (Danio rerio) muscle ankyrin repeat proteins reveals their conserved response to endurance exercise. PLoS One. 13:e0204312