Address book

Contacts

Staff Structures

SIRIO DUPONT

Back to the list

Position

Professore Ordinario

Structure

Dipartimento di Medicina Molecolare - DMM

Address

VIA U. BASSI, 58/B - PADOVA

Telephone

0498276095

E-mail

sirio.dupont@unipd.it

Notices

Teachings

Publications

Selected Publications:
Dupont, S., Zacchigna, L., Cordenonsi, M., Soligo, S., Adorno, M., Rugge, M. & Piccolo, S. Germ-layer specification and control of cell growth by Ectodermin, a Smad4 ubiquitin ligase. Cell 121, 87–99 (2005).
Dupont, S., Mamidi, A., Cordenonsi, M., Montagner, M., Zacchigna, L., Adorno, M., Martello, G., Stinchfield, M. J., Soligo, S., Morsut, L., Inui, M., Moro, S., Modena, N., Argenton, F., Newfeld, S. J. & Piccolo, S. FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell 136, 123–135 (2009).
Morsut, L., Yan, K.-P., Enzo, E., Aragona, M., Soligo, S. M., Wendling, O., Mark, M., Khetchoumian, K., Bressan, G., Chambon, P., Dupont, S., Losson, R. & Piccolo, S. Negative control of Smad activity by ectodermin/Tif1gamma patterns the mammalian embryo. Development 137, 2571–2578 (2010).
Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S., Elvassore, N. & Piccolo, S. Role of YAP/TAZ in mechanotransduction. Nature 474, 179–183 (2011).
Halder, G., Dupont, S. & Piccolo, S. Transduction of mechanical and cytoskeletal cues by YAP and TAZ. Nat. Rev. Mol. Cell Biol. 13, 591–600 (2012).
Aragona, M., Panciera, T., Manfrin, A., Giulitti, S., Michielin, F., Elvassore, N., Dupont, S. & Piccolo, S. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell 154, 1047–1059 (2013).
Piccolo, S., Cordenonsi, M. & Dupont, S. Molecular pathways: YAP and TAZ take center stage in organ growth and tumorigenesis. Clin. Cancer Res. 19, 4925–4930 (2013).
Piccolo, S., Dupont, S. & Cordenonsi, M. The biology of YAP/TAZ: hippo signaling and beyond. Physiol. Rev. 94, 1287–1312 (2014).
Sorrentino, G., Ruggeri, N., Specchia, V., Cordenonsi, M., Mano, M., Dupont, S., Manfrin, A., Ingallina, E., Sommaggio, R., Piazza, S., Rosato, A., Piccolo, S. & Del Sal, G. Metabolic control of YAP and TAZ by the mevalonate pathway. Nat. Cell Biol. 16, 357–366 (2014).
Enzo, E., Santinon, G., Pocaterra, A., Aragona, M., Bresolin, S., Forcato, M., Grifoni, D., Pession, A., Zanconato, F., Guzzo, G., Bicciato, S. & Dupont, S. Aerobic glycolysis tunes YAP/TAZ transcriptional activity. EMBO J. 34, 1349–1370 (2015).
Santinon, G., Pocaterra, A. & Dupont, S. Control of YAP/TAZ Activity by Metabolic and Nutrient-Sensing Pathways. Trends Cell Biol. (2015).
Santinon G., Brian I., Pocaterra A., Romani P., Franzolin E., Rampazzo C., Bicciato S. and Dupont S. (2018) dNTP metabolism links mechanical cues and YAP/TAZ to cell growth and oncogene-induced senescence. EMBO J. (2018)
Pocaterra, A., Santinon, G., Romani, P., Brian, I., Dimitracopoulos, A., Ghisleni, A., Carnicer-Lombarte, A., Forcato, M., Braghetta, P., Montagner, M., Galuppini, F., Aragona, M., Pennelli, G., Bicciato, S., Gauthier, N., Franze, K., and Dupont, S. F-actin dynamics regulates mammalian organ growth and cell fate maintenance. J. Hepat (2019).
Romani, P., Brian, I., Santinon, G., Pocaterra, A., Audano, M., Pedretti, S., Mathieu, S., Forcato, M., Bicciato, S., Manneville, J.-B., Mitro, N., Dupont, S. Extracellular matrix mechanical cues regulate lipid metabolism through Lipin-1 and SREBP. Nat. Cell Biol. (2019).

Research Area

We are interested in understanding how the mechanical properties of the extracellular matrix (ECM) regulate signaling pathways, gene transcription and other cellular processes, and how this is relevant for cell behavior, tissue homeostasis and disease. Our goal is to identify novel general principles in vitro, and to push their validation in vivo with the development of new animal models to study mechano-signaling in tissues. We use a multidisciplinary approach that includes custom-built compliant cell culture substrata, ECM micropatterning, cell micromanipulations, optical microscopy, molecular and cell biology techniques, transcriptional and bioinformatic analyses, proteomics, metabolomics, CRISPR/Cas9 modified cell lines, and genetically-modified mice, also thanks to multiple collaborations with colleagues in Italy and abroad. We have identified YAP/TAZ transcriptional coactivators as readers of ECM mechanical cues and mediators of their effects on cancer cell proliferation and mesenchymal stem cell differentiation, and are now developing genetic tools to study the relevance of F-actin remodeling as regulator of YAP/TAZ activity in vivo. Moreover, we got recently interested in understanding how mechanical cues regulate metabolism, with the discovery that ECM-induced cell contractility regulates lipid and cholesterol synthesis by acting on the activity of Golgi-localized SREBP transcription factors.

Thesis proposals

We are interested in understanding how the mechanical properties of the extracellular matrix (ECM) regulate signaling pathways, gene transcription and other cellular processes, and how this is relevant for cell behavior, tissue homeostasis and disease. Our goal is to identify novel general principles in vitro, and to push their validation in vivo with the development of new animal models to study mechano-signaling in tissues. We use a multidisciplinary approach that includes custom-built compliant cell culture substrata, ECM micropatterning, cell micromanipulations, optical microscopy, molecular and cell biology techniques, transcriptional and bioinformatic analyses, proteomics, metabolomics, CRISPR/Cas9 modified cell lines, and genetically-modified mice, also thanks to multiple collaborations with colleagues in Italy and abroad. We have identified YAP/TAZ transcriptional coactivators as readers of ECM mechanical cues and mediators of their effects on cancer cell proliferation and mesenchymal stem cell differentiation, and are now developing genetic tools to study the relevance of F-actin remodeling as regulator of YAP/TAZ activity in vivo. Moreover, we got recently interested in understanding how mechanical cues regulate metabolism, with the discovery that ECM-induced cell contractility regulates lipid and cholesterol synthesis by acting on the activity of Golgi-localized SREBP transcription factors.