MECHANOBIOLOGY OF DISEASE
Giancarlo Forte, Ph.D.
E-mail: giancarlo.forte@fnusa.cz
Tel: +420 511 158 278
Research focus
- The Mechanobiology of Disease (MBD) group is mainly interested in correlating defects in tissue-specific cell mechanobiology system with the onset of aging pathologies, with a specific focus on those affecting the cardiovascular system and cancer. The working hypothesis of MBD is that defects in the function of the apparatus cells use to perceive and respond to external mechanical cues – the mechanosensing apparatus – contribute to aging-associated pathologies.
- MBD researchers adopt loss- and gain-of-function approaches, microfluidics and micropatterning technologies to manipulate the mechanosome of adult, pluripotent stem cells and stem cell-derived cardiac cells. MBD takes advantage of cutting-edge technologies for live imaging, cell separation and high-throughput gene and protein analysis to highlight perturbations in the mechanosensing apparatus occurring in the cardiac tissue and cells derived from patients.
Main goals
- Identification of potential cellular mechanosensors involved in the onset of cardiac pathologies and suitable as bio-markers of the diseases.
- Identification of novel molecular processes involved in cardiac phenotype acquisition.
- Generation of valuable in vitro models of cardiac diseases.
Technological equipment
- Laboratory equipment for cell sorting, analysis, tissue characterization:
- Flow Cytometer, Cell Sorter, Multiphoton Microscope, Magnetic Cell Separator, Bioreactors and stretching machines, Confocal Laser Scanning Microscope suited for live imaging, Enhanced Resolution Confocal Microscope, Real-Time PCR System, Microfluidics devices.
Team Members
- RNDr. Jan Fröhlich, Ph.D. – Principal Investigator, Senior Research Specialist, Senior Postdoctoral Researcher (Budget Administrator (PI)
- Marco Cassani, Ph.D. – Senior Researcher, Senior Postdoctoral Researcher
- Sofia Faes Morazzo, DVM. – Junior Researcher
- Giancarlo Forte, Ph.D. – Researcher, Senior Research Team Leader
- Mgr. Zuzana Garlíková, Ph.D. – Research Specialist
- Dr. Amit Suresh Khairnar – Head Researcher
- Stefania Pagliari, Ph.D. – Senior Postdoctoral Researcher
- Daniel Pereira de Sousa, MSc – Junior Researcher
- Mgr. Helena Skálová – Research Technician
- Mgr. Pavel Šimara, Ph.D. – Postdoctoral Researcher
- MUDr. Pavel Tinka – Research Specialist
- Mgr. Bc. Vladimír Vinarský, Ph.D. – Senior Postdoctoral Researcher
- Mgr. Jan Vrbský, Ph.D. – Senior Postdoctoral Researcher
- MUDr. Danica Zapletalová, Ph.D. – Research Specialist
Team Assistant
Romana Vlčková
Research Coordinator
romana.vlckova@fnusa.cz
Selected results
Perestrelo AR, Silva AC, Oliver-De-La-Cruz J, Martino F, Horváth V, Caluori G, Polanský O, Vinarský V, Azzato G, de Marco G, Žampachová V, Skládal P, Pagliari S, Rainer A, Pinto-do-Ó P, Caravella A, Koci K, Nascimento DS, Forte G. Multiscale Analysis of Extracellular Matrix Remodeling in the Failing Heart. Circ Res (2021) DOI: 10.1161/CIRCRESAHA.120.317685
Oliver-De La Cruz J, Nardone G, Vrbsky J, Pompeiano A, Perestrelo AR, Capradossi F, Melajová K, Filipensky P, Forte G.Substrate mechanics controls adipogenesis through YAP phosphorylation by dictating cell spreading. Biomaterials 2019. doi: 10.1016/j.biomaterials.2019.03.009.
Nardone G, Oliver De La Cruz J, Vrbsky J, Martini C, Pribyl J, Skládal P, Pešl M, Caluori G, Pagliari S, Martino F, Maceckova Z, Hajduch M, Sanz-García A, Pugno NM, Stokin GB, Forte G. YAP regulates cell mechanics by controlling focal adhesion assembly. Nat Commun 2017. doi:10.1038/ncomms15321.
Pagliari S, Vinarsky V, Martino F, Perestrelo AR, Vrbsky J, Oliver-De-La-Cruz J, Caluori G, Skladal P, Zampachova V, Kytyr D, Grassi G, Sampaolesi M, Rainer A, Forte G. YAP-TEAD control of human pluripotent stem cell mechanics guides cardiogenic mesoderm specification. Cell Death Differ (2020) DOI:10.1038/s41418-020-00643-5.
Martino F, Perestrelo AR, Hejret V, Durikova H, Horvath V, Cavalieri F, Caruso F, Albihlal WS, Gerber AP, O’Connell MA, Pagliari S, Forte G. The mechanical regulation of RNA binding protein hnRNPC in the failing heart. BiorXiv 2021, https://doi.org/10.1101/2021.08.27.457906.
Ergir E, Oliver De La Cruz J, Fernandes S, Cassani M, Niro F, Pereira Sousa D, Vrbsky J, Vinarsky V, Perestrelo AR, Debellis D, Cavalieri F, Pagliari S, Redl H, Ertl P, Forte G. Generation and Maturation of Human iPSC-derived Cardiac Organoids in Long Term Culture. BiorXiv 2022, doi: https://doi.org/10.1101/2022.03.07.483273.
Mosqueira D, Pagliari S, Uto K, Ebara M, Romanazzo S, Escobedo-Lucea C, Nakanishi J, Taniguchi A, Franzese O, Di Nardo P, Goumans MJ, Pinto-do-Ó P, Aoyagi T, Forte G. Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure. ACS Nano (2014) 8: 2033-2047.
