Our Research Interests

 

The sensitivity of different cell types to extracellular matrix (ECM) mechanics and nanotopography has been compellingly demonstrated in vitro [1]. In particular, the possibility to trigger stem cell specification [2, 3] as well as to control somatic cell function [4] by modifying substrate elasticity has been confirmed. This evidence led to the speculation that the sudden perturbation in the mechanics and nanotopography occurring at the onset of given pathologies (i.e.: muscle fibrosis, myocardial infarction, neurodegenerative pathologies). Together with the inflammation burst that usually parallels the process, and which is likely to turn into chronic activation of the immune system, this event can induce a change in tissue-resident cell signaling and phenotype and thus impair their function. The detrimental effects of the modification in local ECM composition and ultrastructure on organ function have been highlighted in basically all the tissues.

 

The Center for Translational medicine (CTM) is a highly interdisciplinary research platform in the International Clinical Research Center (ICRC), a EU-funded project of the St. Anne’s University Hospital, Brno, to build its own translational medical research premises. The research center, previously known as Integrated Center for Cell Therapy and Regenerative Medicine (ICCT) currently hosts young promising researchers and students from all over the world (9 nationalities represented) and aims at unveiling the molecular mechanisms involved in the onset and progression of the diseases of aging. For this purpose, CTM adopts original and interdisciplinary approaches based on the use of smart materials, microfluidics systems, bioreactors, mechanically-assisted devices and multi-faceted molecular and cellular biology skills to investigate the molecular basis of complex diseases.

 

CTM is currently articulated in 4 independent but complementary research groups:

 

1) Cardiovascular System Mechanobiology Group (CSM). The group is active and internationally recognized for its studies on the impact of mechanosensor system in determining the onset and progression of cardiovascular pathologies (Dr. Giancarlo Forte;

 

2) Translational Neuroscience and Aging Research Group (TNA), aiming at disclosing the link between the impairment of axonal transport and the occurrence of neurodegenerative pathologies (Dr. Gorazd B. Stokin);

 

3) Cellular and Molecular Immunoregulation Group (CMI). This group is devoted to investigate how acute and chronic inflammation contributes to tissue remodelling during regeneration and ageing (Dr. Jan Fric).

4) Epigenetics in Metabolism and Aging (EMA).  The group aims at unveiling the epigenetics mechanisms of liver cancer progression. Moreover, the group is interested in investigating the effects of short term fasting to treat gastrointestinal cancers (Dr. Manlio Vinciguerra).

CTM also features a newly-built Good Manufacture Practice (GMP) facility. The facility, headed by Dr. Irena Koutna, is the hub for St. Anne's Hospital and the local research community interested in clinical studies.

 

References:

 

[1] Engler AJ, et al. Matrix Elasticity Directs Stem Cell Lineage Specification. Cell 2006; 126: 677-689; [2] Forte G, et al. Criticality of the Biological and Physical Stimuli Array Inducing Resident Cardiac Stem Cell Determination. Stem Cells 2008, 26, 2093-2103; [3] Pagliari S, et al. Cooperation of Biological and Mechanical Signals in Cardiac Progenitor Cell Differentiation. Adv. Mater. 2011, 23, 514-518; [4] Forte G, et al. Substrate Stiffness Modulates Gene Expression and Phenotype in Neonatal Cardiomyocytes In Vitro. Tissue Eng. Part A 2012; 18: 1837-1848; [5] Ebara M, et al. Shape-Memory Surface with Dynamically Tunable Nano-Geometry Activated by Body Heat. Adv. Mater. 2012, 24, 273-278.

 

Publications:

 

 

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

Lacovich V, Espindola S, Alloatti M, Pozo Devoto V, Cromberg L, Carna M, Forte G, Gallo JM, Bruno L, Stokin GB, Avale ME, and Falzone T. Tau isoforms imbalance impairs the axonal transport of the amyloid precursor protein (APP) in human neurons. J Neurosci 2017. pii: 2305-2316.

Scarabel L, Perrone F, Garziera M, Farra R, Grassi M, Musiani F, Russo Spena C, Salis B, De Stefano L, Toffoli G, Rizzolio F, Tonon F, Abrami M, Chiarappa G, Pozzato G, Forte G, Grassi G and Dapas B. Strategies to optimize siRNA delivery to malignant hepatocellular carcinoma cells. Exp Opin Drug Deliv 2017.

T Zelante, A Y W Wong, A Mencarelli, S Foo, F Zolezzi, B Lee, M Poidinger,P Ricciardi-Castagnoli and J Fric. Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis. Mucosal Immunol 2016  doi:10.1038/mi.2016.52

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.

Pagliari S, Romanazzo S, Mosqueira D, Pinto-do-Ó P, Aoyagi T, Forte G. Adult stem cells and biocompatible scaffolds as powerful drug delivery tools for cardiac repair. Curr Med Chem 2013 20: 3429-3447.

Zelante T, Wong AY, Ping TJ, Chen J, Sumatoh HR, Viganò E, Hong Bing Y, Lee B, Zolezzi F, Fric J, Newell EW, Mortellaro A, Poidinger M, Puccetti P, Ricciardi-Castagnoli P. CD103(+) Dendritic Cells Control Th17 Cell Function in the LungCell Rep 2015 Sep 22;12(11):1789-801. doi: 10.1016/j.celrep.2015.08.030. Epub 2015 Sep 10.

Sanz-Garcia A, Oliver De La Cruz J, Mirabet V, Gandía C, Villagrasa A, Sodupe E, Escobedo-Lucea C. Heart valve tissue engineering: how far is the bedside from the bench? Expert Rev Mol Med 2015 Sep 24;17:e16. doi: 10.1017/erm.2015.15.

Perestrelo AR, Aguas ACP, Rainer A, Forte G. Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering. Sensors 2015, 15, 31142–31170

Freire AG*, Nascimento DS*, Forte G*, Valente M, Resende T, Pagliari S, Abreu C, Carvalho I, Lemischka I, Di Nardo P, Pinto-do-Ó P. Stable phenotype and function of immortalized Lin-Sca-1+ cardiac progenitor cells in long-term culture: a step closer to standardization. Stem Cells Dev 2013. DOI:10.1089/scd.2013.0305. *equal contribution.

Forte G, Pagliari S, Ebara U, Uto K, Tam K, Romanazzo S, Escobedo-Lucea C, Romano E, Di Nardo P, Traversa E, Aoyagi T. Substrate stiffness modulates neonatal cardiomyocyte maturation in vitro. Tissue Eng part A (2012). 18: 1837-1848.

Pagliari S, Tirella A, Ahluwalia A, Duim S, Goumans MJ, Aoyagi T, Forte G. A Multistep Procedure To Prepare Pre-Vascularized Cardiac Tissue Constructs Using Adult Stem Cells, Dynamic Cell Cultures And Porous Scaffolds. Front Physiol 2014. doi: 10.3389/fphys.2014.00210.

Escobedo-Lucea C, Bellver C, Gandia C, Lezameta M, Mirabet V, Forte G, Moreno I, Ayuso-Sacido A, Garcia-Verdugo JM. A xenogeneic-free protocol for isolation and expansion of human adipose stem cells for clinical uses. PLoS One 2013; 8: e67870. doi: 10.1371/journal.pone.0067870.

Pagliari S, Jelinek J, Grassi G, Forte G. Targeting pleiotropic signaling pathways to control adult cardiac stem cell fate and function. Front Physiol 2014. doi: 10.3389/fphys.2014.00219.

Di Felice V, Forte G, Coletti D. Biomaterials and bioactive molecules to drive differentiation in striated muscle tissue engineering. Front Physiol 2015. doi:10.3389/fphys.2015.00052.

Romanazzo S, Forte G, Morishima K, Taniguchi A. IL-12 Involvement in Myogenic Differentiation. Biomater Sci 2015 3: 469-479.

Di Felice V, Barone R, Nardone G, Forte G. Cardiac tissue engineering: a reflection after a decade of hurry. Front. Physiol 2014. doi: 10.3389/fphys.2014.00365

Tesarova L, Simara P, Stejskal S, Koutna I. Haematopoietic developmental potential of human pluripotent stem cell lines. Folia Biol (Praha). 2014;60 Suppl 1:90-4.

Simara P, Tesarova L, Padourova S, Koutna I. Generation of human induced pluripotent stem cells using genome integrating or non-integrating methods. Folia Biol (Praha). 2014;60 Suppl 1:85-9.

Simara P, Motl JA, Kaufman DS. Pluripotent stem cells and gene therapy. Transl Res. 2013 Apr;161(4):284-92.

Bendickova K, Tidu F, Fric J, Calcineurin-NFAT signalling in myeloid leukocytes: new prospects and pitfalls in immunosuppressive therapy.  EMBO Mol Med 2017. DOI: 10.15252/emmm.201707698

De Luca A, Pariano M, Cellini B, Costantini C, Villella VR, Jose SS, Palmieri M, Borghi M, Galosi C, Paolicelli G, Maiuri L, Fric J, Zelante T. The IL-17F/IL-17RC Axis Promotes Respiratory Allergy in the Proximal Airways. Cell Rep. 2017 Aug 15;20(7):1667-1680. doi: 10.1016/j.celrep.2017.07.063.

© 2015 by Center for Translational Medicine  (CTM)

International Clinical Research Center (FNUSA-ICRC)

St. Anne's University Hospital

Brno - Czech Republic

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