Mario Lo Bello
e-mail: lobello AT uniroma2.it
affiliation: Università di Roma Tor Vergata
research area(s): Chemical Biology, Cancer Biology
Course:
Cell and Molecular Biology
University/Istitution: Università di Roma Tor Vergata
University/Istitution: Università di Roma Tor Vergata
Mario Lo Bello received his first degree in Biological Sciences (laurea) at the University of Rome "La Sapienza" in 1978. In 1983 he become research scientist in Biochemistry at the University of Chieti, Faculty of Medicine. In 1985, as senior reaearch scientist, he moved to University of Rome "Tor Vergata", Faculty of Sciences M.F.N., Department of Biology. In 2001 he become Associate Professor in Biochemistry and in 2004 he was appointed by the same Faculty of Sciences M.F.N.as Full Professor in Clinical Biochemistry.
He received his PhD in Protein Chemistry in U.K. (University of Cranfield) in 1991.
He received his PhD in Protein Chemistry in U.K. (University of Cranfield) in 1991.
Almost his research has been devoted to the study of glutathione transferases enzymes. He has contributed, by using site directed mutagenesis and in collaboration with crystallography lab (M.W. Parker), to numerous studies on the active site of human GST P1-1 and its catalytic mechanism. Recently, with the aid of proteomic approache and using cellular models and tissues he has focused his reaearch on the role of these antioxidant enzymes in neurodegenerative or cancer diseases under oxidative stress. Among the posttranslational modifications the glutathionylation of proteins seem to be a new promising area of research
PARKER LJ, ITALIANO LC, MORTON CJ, HANCOCK.C, ASCHER DB, AITKEN JB, HARRIS HH, CAMPOMANES P, ROTHLISBERGER U, DE LUCA A, LO BELLO M., ANG WH, DYSON PJ, PARKER MW (2011). Studies of Glutathione Transferase P1-1 Bound to a Platinum(IV)-Based Anticancer Compound Reveal the Molecular Basis of Its Activation. CHEMISTRY-A EUROPEAN JOURNAL, vol. 17; p. 7806-17816,
QUESADA-SORIANO I, PARKER LJ, PRIMAVERA A, WIELENS J, HOLIEN JK, CASAS-SOLVAS JM, BERENGUEL AV, AGUILERA AM, NUCCETELLI M, LO BELLO M., PARKER M.W, CARCIA-FUENTES L (2010). Diuretic drug binding to human glutathione transferase P1-1: potential role of Cys-101 revealed in the double mutant C47S/Y108V. JOURNAL OF MOLECULAR RECOGNITION, vol. 24; p. 220-234,
ANG WH, PARKER LJ, DE LUCA A, JUILLERAT-JEANNERET L, MORTON CJ, LO BELLO M., PARKER MW, DYSON PJ (2009). Rational design of an organometallic glutathione transferase inhibitor. ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, vol. 48; p. 3854-3857.
FABRINI R, DE LUCA A, STELLA L, MEI G, ORIONI B, CICCONE S, FEDERICI G, LO BELLO M., RICCI G (2009). Monomer/dimer equilibrium in glutathione transferases: a critical re-examination. BIOCHEMISTRY,
QUESADA-SORIANO I, PARKER LJ, PRIMAVERA A, CASAS-SOLVAS JM, BERENGUEL AV, BARÓN C, MORTON CJ, MAZZETTI AP, LO BELLO M., PARKER MW, GARCÍA-FUENTES L (2009). Influence of the H-site residue 108 on human glutathione transferase P1-1 ligand binding: Structure-thermodynamic relationships and thermal stability. PROTEIN SCIENCE,
PARKER LJ, CICCONE S, ITALIANO LC, PRIMAVERA A, OAKLEY AJ, MORTON CJ, HANCOCK NC, LO BELLO M., AND PARKER M W (2008). The Anti-cancer Drug Chlorambucil as a Substrate for the Human Polymorphic Enzyme GlutathioneTransferase P1-1: Kinetic Properties and Crystallographic Characterisation of Allelic Variants. JOURNAL OF MOLECULAR BIOLOGY, vol. 380; p. 131-144,
PRIMAVERA A, FUSTINONI S, BIROCCIO A, BALLERINI S, URBANI A, BERNARDINI S, FEDERICI G, CAPUCCI E, MANNO M, LO BELLO M. (2008). Glutathione Transferases and Glutathionylated Hemoglobin in Workers Exposed to Low Doses of 1,3-Butadiene. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, vol. 17; p. 3004-30012,
ANG WH, DE LUCA A, CHAPUIS-BERNASCONI C, JUILLERAT-JEANNERET L, LO BELLO M., DYSON PJ (2007). Organometallic Ruthenium Inhibitors of Glutathione-S-Transferase P1-1 as Anticancer Drugs. CHEMMEDCHEM, vol. 2; p. 1799-1806,
STELLA L, PALLOTTINI V, MORENO S, LEONI S, DE MARIA F, TURELLA P, FEDERICI G, FABRINI R, DAWOOD KF, LO BELLO M., PEDERSEN JZ, RICCI G (2007). Electrostatic association of glutathione transferase to the nuclear membrane. THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 282; p. 6372-6379,
TELLEZ-SANZ, R. CESAREO, E. NUCCETELLI, M. AGUILERA, M.A. BARON, C. PARKER, L.ADAMS, J.J. MORTON, LO BELLO M., PARKER M.W. AND GARCIA-FUENTES L (2006). Calorimetric and structural studies of the nitric oxide carrier S-nitrosoglutathione bound to human glutathione transferase P1-1. PROTEIN SCIENCE, vol. 15; p. 1093-1105,
CESAREO E, PARKER LJ, PEDERSEN JZ, NUCCETELLI M, MAZZETTI AP, PASTORE A, FEDERICI G, CACCURI AM, RICCI G, ADAMS JJ, PARKER MW, LO BELLO M. (2005). Nitrosylation of human glutathione transferase P1-1 with dinitrosyl diglutathionyl iron complex in vitro and in vivo. THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 280; p. 42172-42180,
LIEBAU E, DE MARIA F, BAUMEISTER C, PERBANDT M, TURELLA P, ANTONINI G, FEDERICI G, GIANSANTI F, STELLA L, LO BELLO M., CACCURI AM, RICCI G (2005). Cooperativity and pseudo-cooperativity in the glutathione S-transferase from Plasmodium falciparum. THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 280; p. 26121-26128,
QUESADA-SORIANO I, PARKER LJ, PRIMAVERA A, WIELENS J, HOLIEN JK, CASAS-SOLVAS JM, BERENGUEL AV, AGUILERA AM, NUCCETELLI M, LO BELLO M., PARKER M.W, CARCIA-FUENTES L (2010). Diuretic drug binding to human glutathione transferase P1-1: potential role of Cys-101 revealed in the double mutant C47S/Y108V. JOURNAL OF MOLECULAR RECOGNITION, vol. 24; p. 220-234,
ANG WH, PARKER LJ, DE LUCA A, JUILLERAT-JEANNERET L, MORTON CJ, LO BELLO M., PARKER MW, DYSON PJ (2009). Rational design of an organometallic glutathione transferase inhibitor. ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, vol. 48; p. 3854-3857.
FABRINI R, DE LUCA A, STELLA L, MEI G, ORIONI B, CICCONE S, FEDERICI G, LO BELLO M., RICCI G (2009). Monomer/dimer equilibrium in glutathione transferases: a critical re-examination. BIOCHEMISTRY,
QUESADA-SORIANO I, PARKER LJ, PRIMAVERA A, CASAS-SOLVAS JM, BERENGUEL AV, BARÓN C, MORTON CJ, MAZZETTI AP, LO BELLO M., PARKER MW, GARCÍA-FUENTES L (2009). Influence of the H-site residue 108 on human glutathione transferase P1-1 ligand binding: Structure-thermodynamic relationships and thermal stability. PROTEIN SCIENCE,
PARKER LJ, CICCONE S, ITALIANO LC, PRIMAVERA A, OAKLEY AJ, MORTON CJ, HANCOCK NC, LO BELLO M., AND PARKER M W (2008). The Anti-cancer Drug Chlorambucil as a Substrate for the Human Polymorphic Enzyme GlutathioneTransferase P1-1: Kinetic Properties and Crystallographic Characterisation of Allelic Variants. JOURNAL OF MOLECULAR BIOLOGY, vol. 380; p. 131-144,
PRIMAVERA A, FUSTINONI S, BIROCCIO A, BALLERINI S, URBANI A, BERNARDINI S, FEDERICI G, CAPUCCI E, MANNO M, LO BELLO M. (2008). Glutathione Transferases and Glutathionylated Hemoglobin in Workers Exposed to Low Doses of 1,3-Butadiene. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, vol. 17; p. 3004-30012,
ANG WH, DE LUCA A, CHAPUIS-BERNASCONI C, JUILLERAT-JEANNERET L, LO BELLO M., DYSON PJ (2007). Organometallic Ruthenium Inhibitors of Glutathione-S-Transferase P1-1 as Anticancer Drugs. CHEMMEDCHEM, vol. 2; p. 1799-1806,
STELLA L, PALLOTTINI V, MORENO S, LEONI S, DE MARIA F, TURELLA P, FEDERICI G, FABRINI R, DAWOOD KF, LO BELLO M., PEDERSEN JZ, RICCI G (2007). Electrostatic association of glutathione transferase to the nuclear membrane. THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 282; p. 6372-6379,
TELLEZ-SANZ, R. CESAREO, E. NUCCETELLI, M. AGUILERA, M.A. BARON, C. PARKER, L.ADAMS, J.J. MORTON, LO BELLO M., PARKER M.W. AND GARCIA-FUENTES L (2006). Calorimetric and structural studies of the nitric oxide carrier S-nitrosoglutathione bound to human glutathione transferase P1-1. PROTEIN SCIENCE, vol. 15; p. 1093-1105,
CESAREO E, PARKER LJ, PEDERSEN JZ, NUCCETELLI M, MAZZETTI AP, PASTORE A, FEDERICI G, CACCURI AM, RICCI G, ADAMS JJ, PARKER MW, LO BELLO M. (2005). Nitrosylation of human glutathione transferase P1-1 with dinitrosyl diglutathionyl iron complex in vitro and in vivo. THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 280; p. 42172-42180,
LIEBAU E, DE MARIA F, BAUMEISTER C, PERBANDT M, TURELLA P, ANTONINI G, FEDERICI G, GIANSANTI F, STELLA L, LO BELLO M., CACCURI AM, RICCI G (2005). Cooperativity and pseudo-cooperativity in the glutathione S-transferase from Plasmodium falciparum. THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 280; p. 26121-26128,
Project Title:
In vitro and in vivo glutathionylation of proteins involved in epigenetic regulatory mechanisms
Epigenetic modifications represent mechanisms by wich cells may effectively translate multiple signals into different phenotypes. Numerous epigenetic marks such as histone acetylation, methylation and ADP-ribosylation have been characterized to investigate their role in controlling the gene expression in health and disease. However, very little is known about the redox metabolism and epigentic control. Our lab has a longtime experience in the field of GSH and GST enzymes and recently we have addressed the issue of detoxification of high concentration of nitric oxide inside the cells. It appeared that this molecule, present as intracellular GSNO, might affect the expression of certain genes critical for cell survival trough post translational modifications of nuclear proteins (histones) involved in the chromatin folding. The aim of this project is to study in vitro by NMR and/or crystallogaphy the close interaction between these proteins and GST/GSH and in the same time to investigate protein trasport and formation of this complex between histones and cytosolic proteins in available cellular models by using the most relevant cell biology approaches.