Gianluca Baldanzi
e-mail: gianluca.baldanzi AT med.unipmn.it
affiliation: Università del Piemonte Orientale
research area(s): Cancer Biology, Immunity And Infection
Course:
Biotechnologies For Human Health
University/Istitution: Università del Piemonte Orientale
University/Istitution: Università del Piemonte Orientale
Education
"" 23 April 2008 Phd in Molecular Medicine at the "A. Avogadro" University.
"" 6 November 2002 "Specializzazione" cum laude in Clinical Biochemistry at Turin University.
"" 9 July 1998: "Laurea" cum laude in Biological Sciences at Turin University.
Positions
"" 2008-now Assistant professor (ricercatore) at the "A. Avogadro" University
"" 2008 Visiting Scientist at the Institute of Cell and Molecular Science, Queen Mary University of London
"" 2007-2008 fellowship for study and research training on the project "Estrogen and estrogen related compounds signalling pathways in platelets functions and proliferation", scientific advisor Prof. F. Sinigaglia
"" 2004-2007 Graduate fellow in the "E. Menni" scientific park of the Brescia hospital under the supervision of Dr. O. Parolini works on the role of SAP in signal transduction and the possible interation with Dgk-a.
"" 2002-2004 Graduate fellow in the laboratory of Prof. A. Graziani at Department of Medical Sciences of "A. Avogadro" University studying the involvement of Dgk-a activity in cell transformation and tumor promoted angiogenesis
"" 1998-2002 Under-graduate fellow in the laboratory of Prof. Graziani at the Department of Genetics, Biology and Biochemistry of Turin University and later at the Department of Medical Sciences of "A. Avogadro" University, under the supervision of Prof. A. Graziani. Works on the non-endocrine effects of the Ghrelin hormone and synthetic derivates.
"" 1996-1998 Student in the laboratory of Prof. Graziani, at the Department of Genetics, Biology and Biochemistry of Turin University. Works on the regulation of Dgk-a activity by Src and growth factors such as VEGF and HGF.
Research Fellowships
"" 2008 EMBO Short Term Fellowship for International Mobility
"" February 2007-February 2008 fellowship for study and research training on the project "Estrogen and estrogen related compounds signalling pathways in platelets functions and proliferation", scientific advisor Prof. F. Sinigaglia.
"" March 2004-February 2007 research contract in the science center "E. Menni" (Brescia, Italy) in the project "Function and regulation of SAP/SH2D1A in T lymphocyte", scientific advisor Dr. O. Parolini.
"" 2000-2003 Three years fellowship from Italian Federation for Cancer Research with a project entitled "Evaluation of aDGK role in cell transformation", scientific advisor Prof. A. Graziani.
"" 1998-2000 Two years fellowship from Turin University
Teaching Experience
Professor of Biochemistry at A. Avogadro University, faculty of medicine:
2010-2011 "Biochemistry laboratory" for biotechnologist.
2008-2011 "Introduction in biochemistry" for technicians.
2007-2010 "Biochemistry and molecular biology" course for laboratory technicians.
2003-2011 "Clinical biochemistry" for biotechnologist.
"" 23 April 2008 Phd in Molecular Medicine at the "A. Avogadro" University.
"" 6 November 2002 "Specializzazione" cum laude in Clinical Biochemistry at Turin University.
"" 9 July 1998: "Laurea" cum laude in Biological Sciences at Turin University.
Positions
"" 2008-now Assistant professor (ricercatore) at the "A. Avogadro" University
"" 2008 Visiting Scientist at the Institute of Cell and Molecular Science, Queen Mary University of London
"" 2007-2008 fellowship for study and research training on the project "Estrogen and estrogen related compounds signalling pathways in platelets functions and proliferation", scientific advisor Prof. F. Sinigaglia
"" 2004-2007 Graduate fellow in the "E. Menni" scientific park of the Brescia hospital under the supervision of Dr. O. Parolini works on the role of SAP in signal transduction and the possible interation with Dgk-a.
"" 2002-2004 Graduate fellow in the laboratory of Prof. A. Graziani at Department of Medical Sciences of "A. Avogadro" University studying the involvement of Dgk-a activity in cell transformation and tumor promoted angiogenesis
"" 1998-2002 Under-graduate fellow in the laboratory of Prof. Graziani at the Department of Genetics, Biology and Biochemistry of Turin University and later at the Department of Medical Sciences of "A. Avogadro" University, under the supervision of Prof. A. Graziani. Works on the non-endocrine effects of the Ghrelin hormone and synthetic derivates.
"" 1996-1998 Student in the laboratory of Prof. Graziani, at the Department of Genetics, Biology and Biochemistry of Turin University. Works on the regulation of Dgk-a activity by Src and growth factors such as VEGF and HGF.
Research Fellowships
"" 2008 EMBO Short Term Fellowship for International Mobility
"" February 2007-February 2008 fellowship for study and research training on the project "Estrogen and estrogen related compounds signalling pathways in platelets functions and proliferation", scientific advisor Prof. F. Sinigaglia.
"" March 2004-February 2007 research contract in the science center "E. Menni" (Brescia, Italy) in the project "Function and regulation of SAP/SH2D1A in T lymphocyte", scientific advisor Dr. O. Parolini.
"" 2000-2003 Three years fellowship from Italian Federation for Cancer Research with a project entitled "Evaluation of aDGK role in cell transformation", scientific advisor Prof. A. Graziani.
"" 1998-2000 Two years fellowship from Turin University
Teaching Experience
Professor of Biochemistry at A. Avogadro University, faculty of medicine:
2010-2011 "Biochemistry laboratory" for biotechnologist.
2008-2011 "Introduction in biochemistry" for technicians.
2007-2010 "Biochemistry and molecular biology" course for laboratory technicians.
2003-2011 "Clinical biochemistry" for biotechnologist.
"" Function and regulation of SAP/SH2D1A gene in T lymphocyte at the Department of Medical Sciences of "A. Avogadro" University in collaboration with Dr. Ornella Parolini from the "E. Menni" scientific park of the Brescia hospital.
"" Signalling pathways promoting hepatocyte survival in preconditioned liver; investigating the activation of intracellular mediators such as PI3K, Src and diacylglycerol kinase upon adenosine and glicine release during preconditioning. In collaboration with Prof. R. Carini at the Department of Medical Sciences.
"" Study of the antiapoptotic proprieties of the new hormone Ghrelin and its synthetic derivates in the group of Prof. A. Graziani; initially at the Department of Genetics, Biology and Biochemistry of Turin University and following at the Department of Medical Sciences of "A. Avogadro" University.
"" Determination of alpha Diacylglycerol kinase requirement for the angiogenetic process, in the group of Prof. A. Graziani at the Department of Medical Sciences of "A. Avogadro" University in collaboration with Prof. F. Bussolino of the molecular angiogenesis laboratory of IRCC, Torino.
"" Study of the biochemical and molecular proprieties of alpha Diacylglycerol kinase and interaction with Src oncogene in the group of Prof. A. Graziani; initially at the Department of Genetics, Biology and Biochemistry of Turin University and following at the Department of Medical Sciences of "A. Avogadro" University.
"" Signalling pathways promoting hepatocyte survival in preconditioned liver; investigating the activation of intracellular mediators such as PI3K, Src and diacylglycerol kinase upon adenosine and glicine release during preconditioning. In collaboration with Prof. R. Carini at the Department of Medical Sciences.
"" Study of the antiapoptotic proprieties of the new hormone Ghrelin and its synthetic derivates in the group of Prof. A. Graziani; initially at the Department of Genetics, Biology and Biochemistry of Turin University and following at the Department of Medical Sciences of "A. Avogadro" University.
"" Determination of alpha Diacylglycerol kinase requirement for the angiogenetic process, in the group of Prof. A. Graziani at the Department of Medical Sciences of "A. Avogadro" University in collaboration with Prof. F. Bussolino of the molecular angiogenesis laboratory of IRCC, Torino.
"" Study of the biochemical and molecular proprieties of alpha Diacylglycerol kinase and interaction with Src oncogene in the group of Prof. A. Graziani; initially at the Department of Genetics, Biology and Biochemistry of Turin University and following at the Department of Medical Sciences of "A. Avogadro" University.
Baldanzi G, Pietronave S, Locarno D, Merlin S, Porporato P, Chianale F, Filigheddu N, Cantelmo AR, Albini A, Graziani A, Prat M. (2011) Diacylglycerol kinases are essential for HGF-dependent proliferation and motility of Kaposi's Sarcoma cells. Cancer Science.
Federica Chianale, Elena Rainero, Cristina Cianflone, Valentina Bettio, Andrea Pighini, Paolo E. Porporato, Nicoletta Filigheddu, Guido Serini, Fabiola Sinigaglia, Gianluca Baldanzi, Andrea Graziani. (2010) Diacylglycerol Kinase α mediates HGF-induced Rac Activation and membrane Ruffling by regulating atypical PKC and RhoGDI. Proceedings Of The National Academy Of Sciences USA, 2010 Mar 2;107(9):4182-7.
G Baldanzi, E Alchera, C Imarisio, M Gaggianesi, CD Ponte, P Nitti, C Domenicotti, WJ van Blitterswijk, E Albano, A Graziani and R Carini. (2010) Negative regulation of diacylglycerol kinase theta mediates adenosine-dependent hepatocyte preconditioning. Cell Death and Differentiation, 2010 Jun;17(6):1059-68.
Yang JS, Gad H, Lee SY, Mironov A, Zhang L, Beznoussenko GV, Valente C, Turacchio G, Bonsra AN, Du G, Baldanzi G, Graziani A, Bourgoin S, Frohman MA, Luini A, Hsu VW. (2008) A role for phosphatidic acid in COPI vesicle fission yields insights into Golgi maintenance. Nat Cell Biol. 2008 Oct;10(10):1146-53.
Guidetti GF, Lova P, Bernardi B, Campus F, Baldanzi G, Graziani A, Balduini C, Torti M. (2008) The Gi-coupled P2Y12 receptor regulates diacylglycerol-mediated signaling in human platelets. J Biol Chem. 2008 Oct 24;283(43):28795-805.
F. Chianale, S. Cutrupi, E. Rainero, G. Baldanzi, P.E. Porporato, S. Traini, N. Filigheddu, V.F. Gnocchi, M.M. Santoro, O. Parolini, Wim J. van Blitterswijk, F. Sinigaglia and A. Graziani (2007) Diacylglycerol kinase-α mediates HGF-induced epithelial cell scatter by regulating Rac activation and membrane ruffling
Mol Biol Cell. 2007 Dec;18(12):4859-71.
G. Baldanzi, S. Cutrupi, F. Chianale, V. Gnocchi, E. Rainero, P. Porporato, N. Filigheddu, W.J. Blitterswijk, O. Parolini, F. Bussolino, F. Sinigaglia and A. Graziani (2008) Diacylglycerol Kinase-alpha Phosphorylation By Src On Y335 Is Required For Activation, Membrane Recruitment And Hgf Induced Cell Motility
Oncogene. 2008 Feb 7;27(7):942-56.
Filigheddu N, Cutrupi S, Porporato PE, Riboni F, Baldanzi G, Chianale F, Fortina E, Piantanida P, De Bortoli M, Vacca G, Graziani A, Surico N. (2007) Diacylglycerol kinase is required for HGF-induced invasiveness and anchorage-independent growth of MDA-MB-231 breast cancer cells.
Anticancer Research 2007 May-Jun;27(3B):1489-92.
N. Filigheddu, V.F. Gnocchi, M. Coscia, M. Cappelli, P.E. Porporato, R. Taulli, S. Traini, G. Baldanzi, F. Chianale, S. Cutrupi, E. Arnoletti, C. Ghè, A. Fubini, N. Surico, F. Sinigaglia, C. Ponzetto, G. Muccioli, T. Crepaldi, A. Graziani (2007)
Ghrelin and des-acyl ghrelin promote differentiation and fusion of c2c12 skeletal muscle cells. Molecular Biology of the Cell 2007 Mar;18(3):986-94
R. Carini, E. Alchera, G. Baldanzi, D. Piranda, R. Splendore, M.G. De Cesaris, P. Caraceni, A. Graziani, E. Albano. (2007) Role of p38 map kinase in glycine-induced hepatocyte resistance to hypoxic injury Journal of Hepatology 2007 Apr;46(4):692-9
Carini R, Alchera E, De Cesaris MG, Splendore R, Piranda D, Baldanzi G, Albano E. (2006) Purinergic P2Y(2) receptors promote hepatocyte resistance to hypoxia.
Journal of Hepatology 45 (2006) 236-245
Federica Chianale, Elena Rainero, Cristina Cianflone, Valentina Bettio, Andrea Pighini, Paolo E. Porporato, Nicoletta Filigheddu, Guido Serini, Fabiola Sinigaglia, Gianluca Baldanzi, Andrea Graziani. (2010) Diacylglycerol Kinase α mediates HGF-induced Rac Activation and membrane Ruffling by regulating atypical PKC and RhoGDI. Proceedings Of The National Academy Of Sciences USA, 2010 Mar 2;107(9):4182-7.
G Baldanzi, E Alchera, C Imarisio, M Gaggianesi, CD Ponte, P Nitti, C Domenicotti, WJ van Blitterswijk, E Albano, A Graziani and R Carini. (2010) Negative regulation of diacylglycerol kinase theta mediates adenosine-dependent hepatocyte preconditioning. Cell Death and Differentiation, 2010 Jun;17(6):1059-68.
Yang JS, Gad H, Lee SY, Mironov A, Zhang L, Beznoussenko GV, Valente C, Turacchio G, Bonsra AN, Du G, Baldanzi G, Graziani A, Bourgoin S, Frohman MA, Luini A, Hsu VW. (2008) A role for phosphatidic acid in COPI vesicle fission yields insights into Golgi maintenance. Nat Cell Biol. 2008 Oct;10(10):1146-53.
Guidetti GF, Lova P, Bernardi B, Campus F, Baldanzi G, Graziani A, Balduini C, Torti M. (2008) The Gi-coupled P2Y12 receptor regulates diacylglycerol-mediated signaling in human platelets. J Biol Chem. 2008 Oct 24;283(43):28795-805.
F. Chianale, S. Cutrupi, E. Rainero, G. Baldanzi, P.E. Porporato, S. Traini, N. Filigheddu, V.F. Gnocchi, M.M. Santoro, O. Parolini, Wim J. van Blitterswijk, F. Sinigaglia and A. Graziani (2007) Diacylglycerol kinase-α mediates HGF-induced epithelial cell scatter by regulating Rac activation and membrane ruffling
Mol Biol Cell. 2007 Dec;18(12):4859-71.
G. Baldanzi, S. Cutrupi, F. Chianale, V. Gnocchi, E. Rainero, P. Porporato, N. Filigheddu, W.J. Blitterswijk, O. Parolini, F. Bussolino, F. Sinigaglia and A. Graziani (2008) Diacylglycerol Kinase-alpha Phosphorylation By Src On Y335 Is Required For Activation, Membrane Recruitment And Hgf Induced Cell Motility
Oncogene. 2008 Feb 7;27(7):942-56.
Filigheddu N, Cutrupi S, Porporato PE, Riboni F, Baldanzi G, Chianale F, Fortina E, Piantanida P, De Bortoli M, Vacca G, Graziani A, Surico N. (2007) Diacylglycerol kinase is required for HGF-induced invasiveness and anchorage-independent growth of MDA-MB-231 breast cancer cells.
Anticancer Research 2007 May-Jun;27(3B):1489-92.
N. Filigheddu, V.F. Gnocchi, M. Coscia, M. Cappelli, P.E. Porporato, R. Taulli, S. Traini, G. Baldanzi, F. Chianale, S. Cutrupi, E. Arnoletti, C. Ghè, A. Fubini, N. Surico, F. Sinigaglia, C. Ponzetto, G. Muccioli, T. Crepaldi, A. Graziani (2007)
Ghrelin and des-acyl ghrelin promote differentiation and fusion of c2c12 skeletal muscle cells. Molecular Biology of the Cell 2007 Mar;18(3):986-94
R. Carini, E. Alchera, G. Baldanzi, D. Piranda, R. Splendore, M.G. De Cesaris, P. Caraceni, A. Graziani, E. Albano. (2007) Role of p38 map kinase in glycine-induced hepatocyte resistance to hypoxic injury Journal of Hepatology 2007 Apr;46(4):692-9
Carini R, Alchera E, De Cesaris MG, Splendore R, Piranda D, Baldanzi G, Albano E. (2006) Purinergic P2Y(2) receptors promote hepatocyte resistance to hypoxia.
Journal of Hepatology 45 (2006) 236-245
Project Title:
Diacylglycerol kinase alpha produced phosphatidic acid controls myosin light chain kinase localization and activity in HGF stimulated epithelial cells
Diacylglycerol kinases (DGKs) regulate lipid signaling by phosphorylating diacylglycerol to phosphatidic acid (PA). Membrane recruitment and activation of DGK-alpha (DGK��) is required for cell proliferation, migration and matrix invasion induced by growth factor, chemokines and oncogenes in epithelial and endothelial cells.
Through a proteomic approach we identified 76 proteins associated to tyrosine phosphorylated DGK�� in Kaposi sarcoma cells. Among these proteins we selected non-muscle myosin light chain kinase (MLCK), for further characterization. MLCK is a regulator of acto-myosin driven contraction, which phosphorylates myosin light chain (MLC). DGK�� co-immunoprecipitates with both long (non-muscle) and short (smooth muscle) MLCK isoforms, consistently with the interaction observed with the proteomic strategy.
Inhere we show that in epithelial cells:
i) HGF-induced activation of DGK�� produces PA at the nascent ruffle;
ii) DGK��-mediated PA generation is necessary and sufficient to recruit MLCK at ruffling site were MLCK promotes ruffle extension;
iii) expression of a constitutively active and membrane-bound DGK�� mutant induces ruffles formation by recruiting MLCK at plasma membrane and promoting MLCK-mediated MLC phosphorylation;
iv) expression of constitutively active MLCK is sufficient to lead to ruffle assembly independently from DGK�� activity.
Altogether those data indicate that PA produced by HGF-induced activation of DGK��, is a novel regulator of the localization and the activity of MLCK required for ruffle formation in epithelial cells.
Through a proteomic approach we identified 76 proteins associated to tyrosine phosphorylated DGK�� in Kaposi sarcoma cells. Among these proteins we selected non-muscle myosin light chain kinase (MLCK), for further characterization. MLCK is a regulator of acto-myosin driven contraction, which phosphorylates myosin light chain (MLC). DGK�� co-immunoprecipitates with both long (non-muscle) and short (smooth muscle) MLCK isoforms, consistently with the interaction observed with the proteomic strategy.
Inhere we show that in epithelial cells:
i) HGF-induced activation of DGK�� produces PA at the nascent ruffle;
ii) DGK��-mediated PA generation is necessary and sufficient to recruit MLCK at ruffling site were MLCK promotes ruffle extension;
iii) expression of a constitutively active and membrane-bound DGK�� mutant induces ruffles formation by recruiting MLCK at plasma membrane and promoting MLCK-mediated MLC phosphorylation;
iv) expression of constitutively active MLCK is sufficient to lead to ruffle assembly independently from DGK�� activity.
Altogether those data indicate that PA produced by HGF-induced activation of DGK��, is a novel regulator of the localization and the activity of MLCK required for ruffle formation in epithelial cells.