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Laboratory of Cell Biology and Biochemistry of Bioactive Lipids

Coordinator

Name : Chiara Donati

Position: Full Professor of Cell Biology

e-mail: chiara.donati@unifi.it

telephone number: +39 055-2751204

 

Brief biographical sketch of the Coordinator

Chiara Donati received her Master Degree (M.Sc.) in Biological Sciences (1998), her residency in Biochemistry and Clinical Chemistry (2002) and her PhD (D.Phil) in Biochemistry and Applied Biology (2006) at the University of Florence in Italy. Her post-doctoral work, performed under the supervision of Prof. Paola Bruni in the field of bioactive lipid mediators and their molecular mechanism in the regulation of fundamental biological functions, was carried out at the University of Florence. From 2000 to 2002 she was visiting fellow at the National Institute of Health in Bethesda, MD, USA. She was Assistant Professor of Cell Biology from 2005 to 2014, Associate Professor of Cell Biology from 2015 to 2024 and she is now Full Professor of Cell Biology at the University of Florence.

She is member of the editorial board of the following journals: Cellular Signaling, Frontiers in Molecular Neuroscience, SL Cell Science and Report, Reproductive Biomedicine Online (RBMO).

Since 2017 she is member of the scientific board of the Doctorate/PhD Program in Biochemistry and Molecular Biology- BIBIM2.0, Università degli Studi di Siena.

She is member of the following Scientific Societies: Società Italiana di Biochimica (SIB) (from 2003); Istituto Interuniversitario di Miologia (IIM) (from 2004); Sphingolipid Club (from 2004); Società Italiana di Biologia e Genetica (AIBG) (from 2005); Associazione di Biologia Cellulare e del Differenziamento (ABCD) (from 2011).

 

Research Team

Francesca Cencetti,

Associate Professor of Biochemistry francesca.cencetti@unifi.it

 

Brief biographical sketch  

Francesca Cencetti received her Master Degree (M.Sc.) in Biological Sciences (1999), her PhD (D.Phil) in Biochemistry and Applied Biology (2003), her residency in Biochemistry and Clinical Chemistry (2008) at the University of Florence in Italy. Her post-doctoral work was performed under the supervision of Prof. Paola Bruni at the University of Florence in the field of bioactive lipid mediators and their biological effects in different cellular models.

She was Contract Professor of Biology from 2006 to 2009, Assistant Professor of Biochemistry from 2009 to 2018 at the University of Florence.

From 2018 she is Associate Professor of Biochemistry. She is review editor for Frontiers in Oncology and Frontiers in Molecular Neuroscience, and reviewer of various journals such as Expert opinion on investigational drugs, Applied Biochemistry and biotechnology, European journal of nutrition, Antioxidant, Scientific Reports, Cells among others.

Since 2015 she is member of the scientific board of the Doctorate/PhD Program in Biochemistry and Molecular Biology- BIBIM2.0, Università degli Studi di Siena.

She is member of Società Italiana di Biochimica (SIB) and Istituto Interuniversitario di Miologia (IIM); Member of the Sphingolipid Club; Member of the Interuniversity Institute of Miology.

 

Caterina Bernacchioni

Associate Professor of  Cell Biology

caterina.bernacchioni@unifi.it

 

Brief biographical sketch

Caterina Bernacchioni received her Master Degree (M.Sc.) in Biological Sciences (2006), her PhD (D.Phil) in Biochemistry and Applied Biology (2011) and her residency in Biochemistry and Clinical Chemistry (2014) at the University of Florence in Italy. During her post-doctoral period, performed under the supervision of Prof. Paola Bruni, she focused her scientific interest on the role of bioactive sphingolipids in the regulation of different biological processes and on the molecular mechanisms implicated. In 2009 and 2016 CB spent research periods at the University of the Basque Country, Bilbao (Spain) and Affichem and Cancer Research Center of Toulouse, Toulouse (France), respectively. She was Assistant Professor of Cell Biology from 2018 to 2023 and she is now Associate Professor of Cell Biology at the University of Florence. CB is review editor for Frontiers in Molecular Biosciences and Frontiers in Molecular Neuroscience and reviewer of different journals such as Cells, Scientific Report, European Journal of Medicinal Chemistry, Journal of Translational Medicine among others.

Since 2023 she is member of the scientific board of the Doctorate/PhD Program in Biochemistry and Molecular Biology- BIBIM2.0. CB is member of the Società Italiana di Biochimica (SIB), of the “Associazione Italiana di Biologia e Genetica Generale e Molecolare” (AIBG), of the “Istituto Interuniversitario di Miologia” (IIM) and of the Sphingolipid Club.

 

Isabelle Seidita, post-doctoral fellow, isabelle.seidita@unifi.it 

Matteo Prisinzano, post-doctoral fellow, matteo.prisinzano@unifi.it

Rebecca Innocenti, post-doctoral fellow, rebecca.innocenti@unifi.it 

Margherita Rossi, PhD student, margherita.rossi@unifi.it 

Maryam Raeispour, PhD student, maryam.raeispour@unifi.it 

Lucia Romeo, PhD student, lucia.romeo@unifi.it 

Gloria Mulas, PhD student, gloria.mulas@edu.unifi.it

 

Research activity background 

  • Role of the bioactive sphingolipid sphingosine 1-phosphate (S1P) in muscle regeneration

Aim of the study was to dissect the impact of the S1P-mediated signaling transduction pathway in the biological response induced by cytokines (TNF alpha, TGF beta), adipokines (adiponectin) and growth factors (PDGF, IGF-1) known to play a physiological and pathological role in the muscle regeneration process.

We showed that the S1P signaling pathway mediates the final biological effect evoked by such molecules. These cytokines and growth factors have been shown to increase the expression and/or activity of sphingosine kinase, the enzyme responsible for the production of S1P, or to modulate the expression of specific sphingolipid receptors. In order to explore a possible functional interplay between S1P and endocannabinoid systems (ECS) in skeletal muscle, we investigated the effect of S1P in the expression of endocannabinoid (eCB) metabolic enzymes and their specific receptors.  S1P was found responsible of the selective up-regulation of Transient Receptor Potential Vanilloid 1 (TRPV1) a positive ion channel, non-canonical receptor for eCB. Moreover, we investigated the role of S1P in eCB-mediated changes in mitochondrial membrane potential and found out the specific involvement of TRPV1.

  • Role of S1P in the biology of adult stem cells.

In studies aimed at characterizing the role of bioactive metabolites of sphingomyelin catabolism in neuronal and epithelial progenitors derived from the otic vesicle, we demonstrated that S1P plays a key role in the regulation of fundamental biological processes such as proliferation, differentiation, survival and migration.

  • Role of theS1P signaling pathway in the molecular mechanisms underlying benign uterine pathologies such as endometriosis, uterine fibroids and adenomyosis

The bioactive sphingolipid signaling pathway has been found to be profoundly altered in these benign uterine pathologies.

In in vitro cellular models of endometriosis, it has been shown that S1P exerts a profound promigratory action and proinflammatory action by increasing the levels of reactive oxygen species and the release of proinflammatory cytokines. In cellular models of uterine fibroids, it has also been shown that the S1P signaling pathway is a crucial mediator of the fibrotic process.

  • Study of the molecular mechanism underlying the neuroprotective effect of S1P in neuronal cell models.

We showed that S1P, following interaction with its specific receptors, reduces the influx of calcium and NMDA receptor activation induced by treatment with amyloid beta peptide oligomers, also by promoting the internalization of the receptor.

 

Current research interests of the laboratory

  • Study of the functional interplay between S1P and endocannabinoid systems (ECS) in skeletal muscle;
  • Role of the S1P signaling pathway in the molecular mechanisms underlying benign uterine pathologies such as endometriosis, uterine fibroids and adenomyosis;
  • Role of S1P in cerebral ischemia. In order to find possible pharmacological targets and prognostic markers of ischemic damage, we are presently investigating the protective role of S1P signaling pathway in the neurodegenerative mechanisms of stroke;
  • Study of the molecular mechanism underlying the neuroprotective effect of S1P in neurodegenerative diseases such as Alzheimer and Parkinson ;
  • Role of S1P signaling pathway in sperm maturation in obesity-related male infertility ;
  • Study of the effect of innovative metal-based photosensitizers in photodynamic therapy (PDT) of tumor cells and pre-neoplastic lesions in the female genital tract.

Collaborations

Prof. Felice Petraglia, Prof. Andrea Galli, Prof.ssa Cristina Cecchi, Prof.ssa Anna Laurenzana, Prof.ssa Anna Maria Pugliese, Prof.ssa Vittoria Colotta, Prof. Claudiu Supuran, Prof. Domenico Edoardo Pellegrini Giampietro e Dott.ssa Elisa Landucci, Università di Firenze;

Prof.ssa Roberta Squecco, Università di Firenze;

Prof.ssa Paola Turano, Prof.ssa Claudia Giorgi, Prof.ssa Barbara Valtancoli, Dott. Luca Conti, Università di Firenze;

Prof.ssa Pasquapina Ciarmela, Università Politecnica delle Marche;

Prof.ssa Paola Piomboni, Università di Siena;

Prof.ssa Rosanna Chianese, Università della Campania;

Prof.ssa Dagmar Meyer zu Heringdorf, Klinikum der Goethe-Universität, Frankfurt am Main, Germany;

Prof. Burkhard Kleuser, Freie Universität Berlin, Germany;

Prof. Webster Santos, Virginia Tech, Blacksburg, USA;

Prof. Kevin Lynch, University of Virginia, USA;

Prof.ssa Cinzia Rapino, Università di Teramo;

Prof. Mauro Maccarrone, Università dell’Aquila;

Prof.ssa Luisa Cigliano, Università degli Studi di Napoli Federico II;

Prof.ssa Maria Letizia Trincavelli, Prof.ssa Chiara Giacomelli, Università di Pisa;

Dr. Vittorio Maglione, Neuromed, Pozzilli (IS).

 

Current/ recent sources of funding (years 2019-2024)

2024 Project Dipartimento di Eccellenza di Scienze Biomediche Sperimentali e Cliniche “Mario Serio”- “Gender differences in the modulation of neutrophil netosis and fibroblast phenotype switch by sphingosine 1-phosphate signaling: implication in pulmonary fibrosis”. Caterina Bernacchioni, principal investigator.

PRIN PNRR2022- “New insights into endometriosis pathogenesis: role of sphingosine 1-phosphate in neutrophil activation”. Caterina Bernacchioni, principal investigator.

PNRR 2022- Missione 4 Componente 2 - finanziato dall’Unione Europea- NextGeneration EU Next, THE Spoke 8 Biotechnology and imaging in neuroscience, Chiara Donati, participant.

PNRR 2022 finanziato dall’Unione Europea- NextGeneration EU Next, THE SPOKE 2. Multi-dimensional omics approach for

PREdicting therapy response of ER+ breast cancers receiving systemic THErapy (PRETHE). Francesca Cencetti, participant

Prin 2022, “Identification of novel molecular mechanisms affecting spermatogenesis, sperm maturation and epigenetic signature in obesity-related male infertility”, Chiara Donati, unit coordinator.

PRIN 2022. Insight into the molecular mechanisms of pulmonary fibrosis: new targets to control the switch from fibrotic to regenerative

fibroblast phenotype – SMILE. Francesca Cencetti, unit coordinator

2020 Project Dipartimento di Eccellenza di Scienze Biomediche Sperimentali e Cliniche “Mario Serio” –Sex steroid hormones and inflammation: possible role of bioactive sphingolipids in endometriosis-induced infertility and pregnancy complications. Chiara Donati, principal investigator.

 

10 best publications (years 2019-2024)

Cencetti F., Bernacchioni C., Bruno M., Squecco R., Idrizaj E., Bruni P., Donati C.

Sphingosine 1-phosphate-mediated activation of ERM contributes to epithelial otic vesicle progenitor differentiation.

Biochim. Biophys. Acta-Mol Cel Res (2019) 1866(4):554-565

PMID: 30611767 DOI: 10.1016/j.bbamcr.2018.12.007

Cencetti F., Bruno G., Bernacchioni C., Japtok L., Puliti E., Donati C, Bruni P.

Sphingosine 1-phosphate lyase blockade elicits myogenic differentiaton of murine myoblasts acting via Spns2/S1P2 receptor axis.

Biochim Biophys Acta-Mol Cell Biol Lipids. (2020) 1865(9):158759.

PMID: 32565314 DOI: 10.1016/j.bbalip.2020.158759

Bruno G, Cencetti F, Pini A, Tondo A, Cuzzubbo D, Fontani F, Strinna V, Buccoliero AM, Casazza G, Donati C, Filippi L, Bruni P, Favre C, Calvani M.

β3-adrenoreceptor blockade reduces tumor growth and increases neuronal differentiation in neuroblastoma via SK2/S1P2 modulation.

Oncogene (2020) 39(2):368-384.

PMID: 31477835 PMCID: PMC6949192 DOI: 10.1038/s41388-019-0993-1

Coppi E, Cherchi F, Fusco I, Dettori I, Gaviano L, Magni G, Catarzi D, Colotta V, Varano F, Rossi F, Bernacchioni C, Donati C, Bruni P, Pedata F, Cencetti F, Pugliese AM.

Adenosine A2B receptors inhibit K+ currents and cell differentiation in cultured oligodendrocyte precursor cells and modulate sphingosine-1-phosphate signaling pathway. 

Biochem Pharmacol. (2020) 177:113956

PMID: 32251679 DOI: 10.1016/j.bcp.2020.113956

Bernacchioni C, Capezzuoli T, Vannuzzi V, Malentacchi F, Castiglione F, Cencetti F, Ceccaroni M, Donati C, Bruni P, Petraglia F.

Sphingosine 1-phosphate receptors are dysregulated in endometriosis: possible implication in transforming growth factor β-induced fibrosis.

Fertil Steril. (2021) 115(2):501-511.

PMID: 32907751 DOI: 10.1016/j.fertnstert.2020.08.012

Bernacchioni C, Ciarmela P, Vannuzzi V, Greco S, Vannuccini S, Malentacchi F, Pellegrino P, Capezzuoli T, Sorbi F, Cencetti F, Bruni P, Donati C, Petraglia F.

Sphingosine 1-phosphate signaling in uterine fibroids: implication in activin A pro-fibrotic effect.

Fertil Steril. (2021) 115(6):1576-1585.

PMID: 33500141 DOI: 10.1016/j.fertnstert.2020.12.022

Bigi A, Cascella R, Fani G, Bernacchioni C, Cencetti F, Bruni P, Chiti F, Donati C, Cecchi C.

Sphingosine 1-phosphate attenuates neuronal dysfunction induced by Amyloid-β oligomers through endocytic internalization of NMDA receptors.

*corresponding authors

FEBS J. (2022) 290(1):112-133

PMID: 35851748 PMCID: PMC10087929 DOI: 10.1111/febs.16579

Standoli S, Pecchioli S, Tortolani D, Di Meo C, Fanti F, Sergi M, Bacci M, Seidita I, Bernacchioni C, Donati C, Bruni P, Maccarrone M, Rapino C, Cencetti F.

The TRPV1 Receptor Is Up-Regulated by Sphingosine 1-Phosphate and Is Implicated in the Anandamide-Dependent Regulation of Mitochondrial Activity in C2C12 Myoblasts.

Int J Mol Sci. (2022) 23(19):11103.

PMID: 36232401 PMCID: PMC9570403 DOI: 10.3390/ijms231911103

Seidita, I., Tusa, I. Prisinzano, M., Menconi A., Cencetti F., Vannuccini S., Castiglione F., Bruni P., Petraglia F., Bernacchioni C., Rovida, E., Donati, C.

Sphingosine 1-phosphate elicits a ROS-mediated proinflammatory response in human endometrial stromal cells via ERK5 activation

FASEB Journal (2023) 37(8), e23061

PMID: 37389926 DOI: 10.1096/fj.202300323R

Prisinzano, M., Bernacchioni, C., Seidita, I., Rossi, M., Raeispour, M., Cencetti, F., Vannuccini, S., Fambrini, M., Petraglia, F., Bruni, P., Donati, C.

Sphingosine 1-phosphate signaling axis mediates neuropeptide S-induced invasive phenotype of endometriotic cells

FEBS J (2024) Apr;291(8):1744-1758.

DOI: 10.1111/febs.17071

Bernacchioni, C., Rossi, M., Vannuzzi, V., Prisinzano, M., Seidita, I., Raeispour, M., Muccilli, A., Castiglione, F., Bruni, P., Petraglia, F., Donati, C.

Sphingosine-1-phosphate receptor 3 is a non-hormonal target to counteract endometriosis-associated fibrosis

Fertil Steril. 2024 Apr;121(4):631-641.

PMID: 38072366 DOI: 10.1016/j.fertnstert.2023.12.007.

 

Ultimo aggiornamento

17.09.2024

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