DUPONT SIRIO

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Structure Department of Molecular Medicine
Telephone 0498276095
Qualification Professore associato confermato
Scientific sector BIO/17 - HISTOLOGY
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Notice and additional information
Il docente è disponibile per il ricevimento studenti su appuntamento. Si consiglia di contattare il docente tramite email spiegando le motivazioni della richiesta di appuntamento, cui farà seguito la comunicazione del giorno e dell'ora per l'incontro.

Proposals for thesis
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, YAP/TAZ and metabolism are reciprocally regulated.

Curriculum Vitae
Education/Training:
1995-2000 Laurea in Molecular Biology, University of Padova, 110/110 summa cum laude.
2000-2003 Ph.D. in Genetics and Molecular Biology of Development, University of Padova. Research advisor: Prof. Stefano Piccolo.
2004-2006 PostDoctorate, University of Padova. Research advisor: Prof. Stefano Piccolo.

Academic activity:
2006-2015 Researcher in Histology and Embriology, School of Medicine, University of Padova. From 2006 Dr. Dupont teaches to first-year Medicine students in the course of ”Histology, Cell biology and Human Embryology” and to fifth-year Medical Biotechnologies students in the course of “Stem Cell Biology”.
2015- Associate Professor in Histology and Embriology, School of Medicine, University of Padova and independent PI.

During his PhD, Dr. Dupont trained in vertebrate early embryonic development, germ layer specification and TGF-beta signalling (Cordenonsi et al., Cell 2003). As a post-doc, he identified a novel TGF-beta regulatory mechanism based on cycles of Smad4 ubiquitination and deubiquitination, relevant for embryonic development from mice to flies (Dupont et al., Cell 2005; Dupont et al., Cell 2009; Morsut et al., Development 2010; Stinchfield et al., Development 2012). He next got interested in how mechanical cues from the cell microenvironment regulate cell function, and led the identification of the YAP/TAZ transcriptional coactivators as readers and mediators of extracellular-matrix mechanical cues(Dupont et al., Nature 2011; Aragona et al., Cell 2013). Lately, as independent principal investigator, he is studying the relevance of mechanical cues for tissue homeostasis, and how mechanical cues and YAP/TAZ regulate other cell phenotypes, including cell metabolism (Enzo et al., EMBO J 2015; Santinon et al., EMBO J 2018).

Lecturer's Curriculum (PDF): 8F7FB35C76311FC4DBFFC2001DFA34B5.pdf

Research areas
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, YAP/TAZ and metabolism are reciprocally regulated.

Publications
Selected Publications:
Cordenonsi, M., Dupont, S., Maretto, S., Insinga, A., Imbriano, C. & Piccolo, S. Links between tumor suppressors: p53 is required for TGF-beta gene responses by cooperating with Smads. Cell 113, 301–314 (2003).
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).
Agricola, E., Randall, R. A., Gaarenstroom, T., Dupont, S. & Hill, C. S. Recruitment of TIF1gamma to chromatin via its PHD finger-bromodomain activates its ubiquitin ligase and transcriptional repressor activities. Mol. Cell 43, 85–96 (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).
Stinchfield, M. J., Takaesu, N. T., Quijano, J. C., Castillo, A. M., Tiusanen, N., Shimmi, O., Enzo, E., Dupont, S., Piccolo, S. & Newfeld, S. J. Fat facets deubiquitylation of Medea/Smad4 modulates interpretation of a Dpp morphogen gradient. Development 139, 2721–2729 (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)

List of taught course units in A.Y. 2018/19
Degree course code (?) Degree course track Course unit code Course unit name Credits Year Period Lang. Teacher in charge
ME1728 COMMON MEL1000195 8 1st Year Second
semester
ITA PAOLA BRUN
ME1729 COMMON MEL1000195 8 1st Year Second
semester
ITA SIRIO DUPONT
ME1934 001PD MEP7079237 8 1st Year First
semester
ENG GIORGIO PALU'
ME1934 002PD MEP7079237 8 1st Year First
semester
ENG GIORGIO PALU'
ME1934 001PD MEP3052685 6 2nd Year First
semester
ENG GRAZIANO MARTELLO
ME1934 002PD MEP3052685 6 2nd Year First
semester
ENG GRAZIANO MARTELLO