• Istituto di Biologia e Patologia Molecolari


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roberto.contestabile@uniroma1.it
ROBERTO CONTESTABILE
Associate Professor

Istitute of Molecular Biology and Pathology - National Research Council
Department of Biochemical Sciences - A. Rossi Fanelli.
My research activity within IBPM concerns a research project lead by Dr Angela Tramonti entitled "Molecular characterization of enzymes involved in vitamin B1- and B6-dependent epilepsies", in collaboration with Victoria Bunik from the Belozersky Research Insitute of Lomonosov Moscow State University (Moscow, Russia).  In this context, our interest is focused on the mechanism of vitamin B6 homeostasis in humans and on the molecular basis of vitamin B6-dependend epilepsy, with particular attention on missense mutations of pyridoxine 5'-phosphate oxidase. We are also collaborating with clinicians to characterise novel mutations and correlate medical symptoms to the biochemical profile of patients.
Tramonti, A., Nardella, C., Di Salvo, M.L., Barile, A., Cutruzzolà, F., Contestabile, R.
Human Cytosolic and Mitochondrial Serine Hydroxymethyltransferase Isoforms in Comparison: Full Kinetic Characterization and Substrate Inhibition Properties (2018) Biochemistry, 57 (51), pp. 6984-6996. 
 
Tramonti, A., Nardella, C., di Salvo, M.L., Pascarella, S., Contestabile, R.
The MocR-like transcription factors: pyridoxal 5′-phosphate-dependent regulators of bacterial metabolism (2018) FEBS Journal, 285 (21), pp. 3925-3944. 
 
Tramonti, A., Paiardini, A., Paone, A., Bouzidi, A., Giardina, G., Guiducci, G., Magnifico, M.C., Rinaldo, S., McDermott, L., Menendez, J.A., Contestabile, R., Cutruzzolà, F.
Differential inhibitory effect of a pyrazolopyran compound on human serine hydroxymethyltransferase-amino acid complexes (2018) Archives of Biochemistry and Biophysics, 653, pp. 71-79. 
 
Giardina, G., Paone, A., Tramonti, A., Lucchi, R., Marani, M., Magnifico, M.C., Bouzidi, A., Pontecorvi, V., Guiducci, G., Zamparelli, C., Rinaldo, S., Paiardini, A., Contestabile, R., Cutruzzolà, F.
The catalytic activity of serine hydroxymethyltransferase is essential for de novo nuclear dTMP synthesis in lung cancer cells (2018) FEBS Journal, 285 (17), pp. 3238-3253. 
 
di Salvo, M.L., Mastrangelo, M., Nogués, I., Tolve, M., Paiardini, A., Carducci, C., Mei, D., Montomoli, M., Tramonti, A., Guerrini, R., Contestabile, R., Leuzzi, V.
Biochemical data from the characterization of a new pathogenic mutation of human pyridoxine-5′-phosphate oxidase (PNPO) (2017) Data in Brief, 15, pp. 868-875. 
 
Tramonti, A., Milano, T., Nardella, C., di Salvo, M.L., Pascarella, S., Contestabile, R.
Salmonella typhimurium PtsJ is a novel MocR-like transcriptional repressor involved in regulating the vitamin 6 (2017) FEBS Journal, 284 (3), pp. 466-484. 
 
Amidani, D., Tramonti, A., Canosa, A.V., Campanini, B., Maggi, S., Milano, T., di Salvo, M.L., Pascarella, S., Contestabile, R., Bettati, S., Rivetti, C.
Study of DNA binding and bending by Bacillus subtilis GabR, a PLP-dependent transcription factor (2017) Biochimica et Biophysica Acta - General Subjects, 1861 (1), pp. 3474-3489. 
ACCESS TYPE: Open Access
SOURCE: Scopus
 
Paiardini, A., Tramonti, A., Schirch, D., Guiducci, G., di Salvo, M.L., Fiascarelli, A., Giorgi, A., Maras, B., Cutruzzolà, F., Contestabile, R.
Differential 3-bromopyruvate inhibition of cytosolic and mitochondrial human serine hydroxymethyltransferase isoforms, key enzymes in cancer metabolic reprogramming (2016) Biochimica et Biophysica Acta - Proteins and Proteomics, 1864 (11), pp. 1506-1517. 
 
Marani, M., Paone, A., Fiascarelli, A., Macone, A., Gargano, M., Rinaldo, S., Giardina, G., Pontecorvi, V., Koes, D., McDermott, L., Yang, T., Paiardini, A., Contestabile, R., Cutruzzolà, F.
A pyrazolopyran derivative preferentially inhibits the activity of human cytosolic serine hydroxymethyltransferase and induces cell death in lung cancer cells (2016) Oncotarget, 7 (4), pp. 4570-
 
Tramonti, A., Fiascarelli, A., Milano, T., Di Salvo, M.L., Nogués, I., Pascarella, S., Contestabile, R.
Molecular mechanism of PdxR - A transcriptional activator involved in the regulation of vitamin B6 biosynthesis in the probiotic bacterium Bacillus clausii (2015) FEBS Journal, 282 (15), pp. 2966-2984. Cited 
 
Di Salvo, M.L., Safo, M.K., Contestabile, R.
Biomedical aspects of pyridoxal 5'-phosphate availability (2012) Frontiers in Bioscience - Elite, 4 E (3), pp. 897-913. 
 
Born: Roma (Italy), 27 February 1967 
Civil Status: married, two daughters
Telephone number: +39 06 49917575
E-mail: roberto.contestabile@uniroma1.it
 
EDUCATION
- Sep. 1997 Ph.D. Degree in Biochemistry at the University of Wales, Cardiff, UK. Final dissertation on "Studies on aspartate aminotransferase and glutamate-1-semialdehyde aminomutase", supervisor Prof. Robert A. John.
- Jul. 1992 Biological Sciences Degree at Sapienza University of Rome, final grade 110/110 cum laude. Dissertation on "Structure-function relationships in serine hydroxymethyltransferase", supervisor Prof. Francesco Bossa.
 
CURRENT POSITION
- Dec. 2010 Associate Professor of Biochemistry, permanent position, at Sapienza University of Rome, Faculty of Pharmacy and Medicine, Dept. of Biochemistry.
- Mar. 2017 Habilitated as full professor of Biochemistry (Bio/10).
 
PREVIOUS WORK EXPERIENCES, FELLOWSHIPS AND AWARDS
- Jul. 2015 Visiting professor at the Department of Chemistry, University of Manitoba, Winnipeg, hosted by Prof. Jörg Stetefeld.
- Sep. 2002 Invited researcher at the Max Planck Institute for Terrestrial Microbiology, Marburg, Germany, hosted by Prof. Rudolf Thauer for a project on “Catalytic and Thermodynamic Properties of Tetrahydromethanopterin-dependent Serine Hydroxymethyltransferase from Methanococcus jannaschii”.
- Feb. 2001 Invited researcher at the Virginia Commonwealth University, Richmond, VA, USA, hosted by Prof. Verne Schirch to work on the catalytic mechanism of threonine aldolase.
- Jan. 2000 Invited researcher at the Virginia Commonwealth University, Richmond, VA, USA, hosted by Prof. Verne Schirch to work on the catalytic mechanism of serine hydroxymethyltransferase.
- Sep. 2000 Researcher Permanent position (10 years) at Sapienza University of Rome, School of Natural Sciences, Physics and Mathematics, Dept. of Biochemistry.
- Apr. 1999 Postdoctoral fellowship (1 year) from the Italian Pasteur Institute - Cenci Bolognetti Foundation to work on the project “Glutamate-1-semialdehyde aminomutase: a potential target of antibacterial drugs” at the Dept. of Biochemical Sciences, Sapienza University of Rome.
- Oct. 1998 Short-term contract (4 months) from the Dept. of Biochemical Sciences, Sapienza University of Rome, to work on the “Production and characterization of site-specific mutant forms of vitamin B6-dependent enzymes”.
- Oct.1997 Postdoctoral fellowship (1 year) from the Italian National Research Council (CNR) to work on the project “Origin of substrate specificity in glutamate semialdehyde-1-aminomutase: a key enzyme in chlorophyll biosynthesis” at the University of Wales, Cardiff, UK.
- Apr. 1996 Award for the best oral presentation at the Annual Meeting of Ph.D. students organized by the British Biochemical Society at the University of Exeter.
- Oct.1995 Research Assistant position (2 years) at the University of Wales, College of Cardiff, UK, to work on a project supported by the British Biotechnology and Biological Sciences Research Council and concerning the catalytic mechanism of glutamate-1-semialdehyde aminomutase.
 
RESEARCH INTERESTS My research activity has mainly concerned the vitamin B6 metabolism, in humans and bacteria, and the mechanism, structure, regulation, metabolic role and inhibition of vitamin B6-dependent enzymes. At present, my interests are focused on the mechanisms of vitamin B6 homeostasis. On one side, I am investigating the transcriptional regulation of vitamin B6 biosynthesis and recycling pathways, focusing on bacterial organisms and the chimeric MocR proteins, which are PLP-binding transcriptional factors involved in the activation or repressor of vitamin B6 metabolism genes. On the other hand, I am studying the role of pyridoxal 5’-phosphate (PLP) carrier proteins, such as pyridoxine 5’-phosphate oxidase (PNPOx), pyridoxal kinase (PLK) and YggS, in controlling PLP homeostasis and delivery to apoenzymes in bacteria and humans. Besides, I am also committed to characterising the molecular basis of vitamin B6-dependend epilepsy, concentrating my attention on missense mutations of human PNPOx. In this context, I am collaborating with clinicians to characterise novel mutations and correlate medical symptoms to the biochemical profile of patients. In recent years, I turned my attention to the role of serine hydroxymethyltransferase in the metabolic reprogramming of cancer cells, participating to two 3-year research programs funded by the Italian Association for Cancer Research (AIRC). My contribution to this field consisted in the study of the catalytic, structural and regulatory properties of both cytosolic and mitochondrial isoforms of the enzyme, the experimentation of novel inhibitors and the devise of in vivo activity assays. Lately, I have been involved in a project concerning the use of B6-enzymes as tools in the biosynthesis of unnatural amino acids and their intracellular incorporation in proteins and peptides.
 
FUNDINGS AND GRANTS
 
As Principal Investigator
- 3-year Research Grant (€ 60,000) funded by the Italian Istituto Pasteur - Fondazione Cenci Bolognetti for a research project entitled “Regulation of vitamin B6 metabolism and bioavailability in Eubacteria” (2018-2020).
- 1-year Research Grant (€ 10.330) funded by Sapienza, University of Rome for a research project entitled “Mechanism and Regulation of Pyridoxal 5’-Phosphate Biosynthesis and Bioavailability” (2012-2013).
- Visiting Professor Grant (€ 3,140) funded by Sapienza, University of Rome for a research project entitled “On the molecular basis of the stereospecificity of glutamate semialdehyde aminomutase”. Invited professor Robert Anthony John, Full Professor, School of Biosciences, Cardiff University, UK (2009).
- 3-year Research Grant (€ 18,000) funded by the Italian Istituto Pasteur - Fondazione Cenci Bolognetti for a research project entitled “Glutamate semialdehyde aminomutase: a potential target of antibacterial agents” (2002-2004).
- 1-year Research Grant (€ 7,000) funded by Sapienza University of Rome (Progetto giovani ricercatori) for a research project entitled “Glutamate 1-semialdehyde aminomutase: a potential target of antimicrobial agents” (2001-2002).
 
As Participant
- Projects funded by AIRC (Italian Association for Cancer Research): two 3-year projects (€ 180,000) entitled “Serine hydroxymethyltransferase as potential target for anticancer therapies” (2013-2015) and “Serine/glycine one-carbon metabolism and cancer: biological role and inhibition of Serine Hydroxymethyltransferase" (2016-2018); 5-year project (€ 370,000) entitled “A Structure-guided Approach to Target the Aurora-A/N-Myc complex in MYCN-amplified Neuroblastoma”.
- FILAS project (2 years; € 218,000) (RU-2014-1020) funded by Regione Lazio to the Dipartimento di Scienze Biochimiche of Sapienza University of Rome, entitled "Piattaforma di sistemi cellulari eucarioti per l'espressione di proteine eterologhe e per lo screening tossicologico di interferenti alimentari, microambientali e bioattivi". Co-principal investigator of the project section entitled ''Espressione, caratterizzazione e produzione in lievito di sostanze ad attività probiotica, antiossidante e citotossica" (2015-2017).
- 3-year Research Grant funded by Istituto Pasteur- Fondazione Cenci Bolognetti (€ 34,000) entitled "Synthesis of pyridoxal phosphate in the vitamin B6 salvage pathway and targeting of the cofactor to apo-enzymes" (2008-2010).
- Several 2-year research projects PRIN (Progetto di Ricerca di Interesse Nazionale) funded by the Italian Ministry of Scientific Research and University in 1999, 2001, 2003, 2005, 2007;
- FIRB (Fondo per gli Investimenti della Ricerca di Base) 2-year project (€ 98,500) funded by the Italian Ministry of Scientific Research and University in 2001;
- Several scientific research projects funded by Sapienza Università di Roma from 2001 to 2017.
 
INTERNATIONAL COLLABORATIONS
- Prof. Jörg Stetefeld, University of Manitoba, Winnipeg, Canada. 
- Prof. Martin Safo, Commonwealth University, Richmond (VA) USA.
- Dr. Tzu-Fun Fu, National Cheng Kung University, Taiwan.
- Dr. Lee Apostol McDermott, University of Pittsburgh, Pennsylvania, USA.
- Prof. Nediljko Budisa, Institut für Chemie, Technische Universität Berlin, Germany.
- Dr. Philippa B. Mills, University College London, UK.
 
 
INVITED SPEAKER in several international (7) and national (3) scientific meetings. 
 
TEACHING ACTIVITIES Biochemistry, Biochemical Methods and Enzymology in Biological Sciences, Industrial Chemistry and Biotechnology courses.
 
SPOKEN LANGUAGES Italian, native language; English, proficient; French, basic.
 
PATENTS AND PARTECIPATION TO SPIN-OFF ACTIVITIES
- Patent pending on "A novel engineered Escherichia coli strain for self-directed in cell production of methionine-derivatives and incorporation into recombinant proteins" in collaboration with Prof. Nediljko Budisa and Prof. Peter Neubauer from Technische Universität Berlin, Germany.
- Co-founder of "SapienZyme", an enzyme assay facility operating within "MoLiRom" spin off of Sapienza Università di Roma (http://www.molirom.com/sapienzyme/).
 
PUBLICATIONS Author of 62 peer-reviewed publications (SCOPUS) in international journals. Author of several chapters in scientific books. Author of Biochemistry and Biochemical Methods textbooks.