• Istituto di Biologia e Patologia Molecolari


Tel :+390649910910
Fax :+39064440062
gianni.colotti@cnr.it
GIANNI COLOTTI
Researcher

Istitute of Molecular Biology and Pathology - National Research Council
Department of Biochemical Sciences -A. Rossi Fanelli.
Sapienza University of Rome - Edificio di Chimica Biologica Piano terra, stanza T11 - P.le A. Moro 5 - 00185 Roma

1.Study of chemical-physical properties and of the physiopathological role of proteins and other macromolecules.

2. Molecular basis of Sorcin activity: calcium-dependent signal transduction, Multidrug resistance, cancer, neurodegenerative diseases.

3. Structural and functional studies on the enzymes of the unique thiol-based redox metabolism of Leishmania, common to all parasites of the Trypanosomatidae family but absent in man.  Development of new therapeutic strategies against leishmaniasis.

4. Small molecules with tRNA-stabilizing effect to rescue disease-causing mitochondrial tRNA point mutations

SELECTED RECENT PUBLICATIONS (last 10 years)

1. Franceschini S., Ilari A, Verzili D, Zamparelli C, Antaramian A, Rueda A, Valdivia HH, Chiancone E, Colotti G.* 
“Molecular basis for the impaired function of the natural F112L sorcin mutant: X-ray crystal structure, calcium affinity, and interaction with annexin VII and the ryanodine receptor”.
FASEB J. Vol. 22(1), pp. 295-306, 2008.  
 
2. Ilari A., Bonamore A., Franceschini S., Fiorillo A., Boffi A., Colotti G.* 
“The X-ray structure of N-methyltryptophan oxidase reveals the structural determinants of substrate specificity”.
Proteins: Structure, Function and Bioinformatics. Vol. 71, No. 4, pp.2065-2075, 2008.       
 
3. Colotti G.*, Zamparelli C., Verzili D., Ilari A. and Chiancone E. 
“Sorcin”.
Calcium Binding Proteins. Vol. 3, No. 1, pp. 14-17, 2008.
 
4. Stefanelli P., Colotti G., Neri A., Salucci M.L., Miccoli R., Di Leandro L., Ippoliti R.
“Molecular Characterization of Nitrite Reductase Gene (aniA) and Gene Product in Neisseria meningitidis Isolates: Is aniA Essential for Meningococcal Survival?”.
IUBMB Life. Vol. 60 (9), pp. 629-636, 2008.  
 
5. Fowler M.R., Colotti G., Chiancone E., Smith G.L. and Fearon I.
”Sorcin modulates cardiac L-type Ca2+ current by functional interaction with the  1C subunit”.
 Experimental Physiology. Vol. 93(12), pp. 1233-1238, 2008.
 
6. Fowler M.R., Colotti G., Chiancone E., Higuchi Y., Seidler T., Smith G.L.
 “Complex modulation of L-type Ca(2+) current inactivation by sorcin in isolated
rabbit cardiomyocytes”.
Pflugers Arch. Vol. 457(5), pp.1049-60, 2009.  
 
7. Baiocco P., Franceschini S., Ilari A, Colotti G.*
“Trypanothione reductase from Leishmania infantum: cloning, expression, purification, crystallization and preliminary X-ray data analysis" 
Protein and Peptide Letters. Vol. 16(2): pp. 196-200, 2009.
 
8. Baiocco P.#, Colotti G.#*, Franceschini S. and Ilari A. 
"Molecular basis of antimony treatment in Leishmaniasis” 
Journal of Medicinal Chemistry. Vol. 52, 2603–2612, 2009.
 
9. Zamparelli C., Macquaide N., Colotti G., Verzili D., Seidler T., Smith G.L. and Chiancone E. 
“Activation of the cardiac Na+–Ca2+ exchanger by sorcin via the interaction of the respective Ca2+-binding domains”.
Journal of Molecular and Cellular Cardiology. Vol. 49 (1), pp.132-41, 2010.
 
10. Colotti G.*, Ilari A.
“Polyamine metabolism in Leishmania: from arginine to trypanothione”. 
Amino Acids. Vol. 40 (2), pp. 269-285, 2011. 
 
11. Baiocco P., Ilari A., Ceci P., Orsini S., Gramiccia M., Di Muccio T., Colotti G.* 
“Inhibitory Effect of Silver Nanoparticles on Trypanothione Reductase Activity and Leishmania infantum Proliferation.” 
ACS Med Chem Lett. Vol. 2 (3): 230–233, 2011.
 
12. Ilari A, Baiocco P, Messori L, Fiorillo A, Boffi A, Gramiccia M, Di Muccio T, Colotti G.* “A gold-containing drug against parasitic polyamine metabolism: the X-ray structure of trypanothione reductase from Leishmania infantum in complex with auranofin reveals a dual mechanism of enzyme inhibition.”
Amino Acids. Vol. 42, 2-3, 803-811, 2012.
 
13. Fiorillo A., Colotti G.#*, Boffi A., Baiocco P., Ilari A. 
“The crystal structures of the Tryparedoxin-Tryparedoxin Peroxidase couple unveil the structural determinants of Leishmania detoxification pathway.“
PLOS Negl. Trop. Dis.  Vol. 6, 8, e1781, 2012.
 
14. Colotti G.*, Ilari A, Boffi A, Morea V. 
“Metals and Metal derivatives in Medicine.” 
Mini Rev Med Chem. Vol. 13, 2, 211-221, 2013.
 
15. Trnkova L.; Ricci D.; Grillo C.; Colotti, G.; Altieri F.
“Green tea catechins can bind and modify ERp57/PDIA3 activity.”
Biochimica et Biophysica Acta. Vol. 1830, 3, 2671-2682, 2013.
 
16. Baiocco P.; Poce G.; Alfonso S.; Cocozza M.; Porretta GC.; Colotti G.*; Biava M.; Moraca F.; Botta M.; Yardley V.; Fiorillo A.; Lantella A.; Malatesta F.; Ilari A.
“Inhibition of Leishmania infantum Trypanothione Reductase by Azole-Based Compounds: a Comparative Analysis with Its Physiological Substrate by X-ray Crystallography.”
ChemMedChem. Vol. 8, 7, 1175-1183, 2013.
 
17. Colotti G.*, Ilari A., Fiorillo A., Baiocco P., Cinellu MA, Maiore L., Scaletti F, Gabbiani C, Messori L.
“Metal‐Based Compounds as Prospective Antileishmanial Agents: Inhibition of Trypanothione Reductase by Selected Gold Complexes.”
ChemMedChem. Vol. 8, 10, 1634-1637, 2013.
 
18. Colotti G.*; Baiocco P.; Fiorillo A.; Boffi A.; Poser E.; Di Chiaro F.; Ilari A.
“Structural insights into the enzymes of the trypanothione pathway: targets for antileishmaniasis drugs.”
Future Medicinal Chemistry. Vol. 5, 15, 1861-1875, 2013.
 
19. Lalioti VS.; Ilari A; O’Connell DJ.; Poser E.; Sandoval IV.; Colotti G.* 
"Sorcin Links Calcium Signaling to Vesicle Trafficking, Regulates Polo-like Kinase 1 and is Necessary for Mitosis."
PLoS One. 2014, Jan 10; 9(1), PONE-D-13-29980R1 10.1371/journal.pone.0085438, 2014.
 
20. Perli E., Giordano C., Pisano A, Montanari A., Campese AF, Reyes A, Ghezzi D, Nasca A, Tuppen HA, Orlandi M, Di Micco P, Poser E, Taylor RW, Colotti G., Francisci S, Morea V, Frontali L, Zeviani M, d’Amati G.
“The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells.”
EMBO Mol. Med. 2014 Feb 1; 6 (2):169-82. doi: 10.1002/emmm.201303198. 
 
21. Sechi S., Colotti G., Belloni G., Mattei V., Frappaolo A., Raffa G.D., Fuller M.T., Giansanti M.G. 
 “GOLPH3 Is Essential for Contractile Ring Formation and Rab11 Localization to the Cleavage Site during Cytokinesis in Drosophila melanogaster. “
PLoS Genet. 2014 May 1;10(5):e1004305. doi: 10.1371/journal.pgen.1004305.
 
22. Masciarelli S, Quaranta R, Iosue I, Colotti G, Padula F, Varchi G, Fazi F, Del Rio A. 
“A small-molecule targeting the microRNA binding domain of argonaute 2 improves the retinoic acid differentiation response of the acute promyelocytic leukemia cell line NB4.”
ACS Chem Biol. 2014 Aug 15;9(8):1674-9. doi: 10.1021/cb500286b. Epub 2014 Jun 11. PubMed PMID: 24914804.
 
23. Colotti G*, Poser E, Fiorillo A, Genovese I, Chiarini V, Ilari A. 
“Sorcin, a calcium binding protein involved in the multidrug resistance mechanisms in cancer cells.” 
Molecules. 2014 Sep 5;19(9):13976-89. doi: 10.3390/molecules190913976. PubMed PMID: 25197934.
 
24. Sechi S., Frappaolo A., Belloni G., Colotti G., Giansanti MG.
 “The multiple cellular functions of the oncoprotein Golgi phosphoprotein 3” 
Oncotarget 2015, 6 (6), 3493.
 
25. Ilari A., Fiorillo A., Baiocco P., Poser E., Angiulli G., Colotti G.*
“Targeting Polyamine Metabolism for Finding New Drugs Against Leishmaniasis: A Review”
Mini reviews in medicinal chemistry 2015, 15 (3), 243-252.
 
26. Angiulli G, Lantella A, Forte E, Angelucci F, Colotti G, Ilari A, Malatesta F.
“Leishmania infantum trypanothione reductase is a promiscuous enzyme carrying an
NADPH:O(2) oxidoreductase activity shared by glutathione reductase”. 
Biochim Biophys Acta. 2015 Sep;1850(9):1891-7. doi:10.1016/j.bbagen.2015.05.022. PubMed PMID: 26033467.
 
27. Brindisi M, Brogi S, Relitti N, Vallone A, Butini S, Gemma S, Novellino E,
Colotti G, Angiulli G, Di Chiaro F, Fiorillo A, Ilari A, Campiani G.
“Structure-based discovery of the first non-covalent inhibitors of Leishmania
major tryparedoxin peroxidase by high throughput docking”. 
Sci Rep. 2015 May 7;5:9705. doi: 10.1038/srep09705. PubMed PMID: 25951439; PubMed Central PMCID: PMC4423475.
 
28. Ilari A, Fiorillo A, Poser E, Lalioti VS, Sundell GN, Ivarsson Y, Genovese I, Colotti G*.
“Structural basis of Sorcin-mediated calcium-dependent signal transduction”. 
Sci Rep. 2015 Nov 18;5:16828. doi: 10.1038/srep16828. PMID: 26577048 
 
29. Perli E, Fiorillo A, Giordano C, Pisano A, Montanari A, Grazioli P, Campese AF, Di Micco P, Tuppen HA, Genovese I, Poser E, Preziuso C, Taylor RW, Morea V, Colotti G*, d'Amati G.
“Short peptides from leucyl-tRNA synthetase rescue disease-causing mitochondrial tRNA point mutations”.
Hum Mol Genet. 2016 Mar 1;25(5):903-15. doi: 10.1093/hmg/ddv619. Epub 2015 Dec 31. PMID: 26721932 
 
30. Digilio, F.A., Lanati, A., Bongiovanni, A., Colotti G., Lacerra, G., Liguori, G.L. 
“Quality-based model for Life Sciences research guidelines”. 
Accreditation and Quality Assurance 2016; 21(3): 221-230.
 
31. Fracasso, G., Falvo, E., Colotti, G., (...), Arcovito, A., Ceci, P. 
“Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness”.
Journal of Controlled Release 2016; 239: 10-18.
 
32. Saccoliti F, Angiulli G, Pupo G, Pescatori L, Madia VN, Messore A, Colotti G, Fiorillo A, Scipione L, Gramiccia M, Di Muccio T, Di Santo R, Costi R, Ilari A.
“Inhibition of Leishmania infantum trypanothione reductase by diaryl sulfide
derivatives”. 
J Enzyme Inhib Med Chem. 2017;32(1):304-310. 
 
33. Ilari A, Fiorillo A, Genovese I, Colotti G*. 
Polyamine-trypanothione pathway: an update. 
Future Med Chem. 2017 Jan;9(1):61-77. 
 
34. Poser E, Genovese I, Masciarelli S, Bellissimo T, Fazi F, Colotti G*. 
Surface Plasmon Resonance: A Useful Strategy for the Identification of Small Molecule
Argonaute 2 Protein Binders. Methods Mol Biol. 2017;1517:223-237. 
 
35. Bellissimo T, Masciarelli S, Poser E, Genovese I, Del Rio A, Colotti G, Fazi F. 
“Small Molecules Targeting the miRNA-Binding Domain of Argonaute 2: From
Computer-Aided Molecular Design to RNA Immunoprecipitation”. 
Methods Mol Biol. 2017;1517:211-221. 
 
36. Mosca L, Falvo E, Ceci P, Poser E, Genovese I, Guarguaglini G, Colotti G*
“Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents”
Applied Sciences 2017, 7, 101.

37: Asteriti IA, Daidone F, Colotti G, Rinaldo S, Lavia P, Guarguaglini G, Paiardini A.
“Identification of small molecule inhibitors of the Aurora-A/TPX2 complex.”
Oncotarget. 2017 Mar 31. 

38. Morea V, Bidollari E, Colotti G, Fiorillo A, Rosati J, De Filippis L, Squitieri F, Ilari A.
“Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure?” 
Amino Acids. 2017. doi: 10.1007/s00726-017-2417-2.  

39: Genovese I, Fiorillo A, Ilari A, Masciarelli S, Fazi F, Colotti G*.
“Binding of doxo- rubicin to Sorcin impairs cell death and increases drug resistance in cancer cells”. 
Cell Death Dis. 2017 Jul 20;8(7):e2950. doi: 10.1038/cddis.2017.342.

40: Ferrara M, Sessa G, Fiore M, Bernard F, Asteriti IA, Cundari E, Colotti G,
Ferla S, Desideri M, Buglioni S, Trisciuoglio D, Del Bufalo D, Brancale A, Degrassi F.
“Small molecules targeted to the microtubule-Hec1 interaction inhibit cancer cell growth through microtubule stabilization”. 
Oncogene. 2017 Sep 18. doi:10.1038/onc.2017.320. 

41: Colotti G*, Fiorillo A, Ilari A.
“Metal-and metalloid-containing drugs for the treatment of trypanosomatid diseases.”
Frontiers in biosciences. 2018. 23, 954-966. doi: 10.2741/4628.
 
42: De Cola A, Franceschini M, Di Matteo A, Colotti G, Celani R, Clemente E, Ippoliti R, Cimini AM, Dhez AC, Vallée B, Raineri F, Cascone I, Destouches D, De Laurenzi V, Courty J, Federici L.
“N6L pseudopeptide interferes with nucleophosmin protein-protein interactions and sensitizes leukemic cells to chemotherapy.”
Cancer Letters. 2018, 412, 272-282. doi: 10.1016/j.canlet.2017.10.038
 
43: Falvo E, Malagrinò F, Arcovito A, Fazi F, Colotti G, Tremante E, Di Micco P, Braca A, 
Opri R, Giuffrè A, Fracasso G, Ceci P. 
“The presence of glutamate residues on the PAS sequence of the stimuli-sensitive nano-ferritin improves in vivo biodistribution and mitoxantrone encapsulation homogeneity.” 
J Control Release. 2018 Feb 20;275:177-185. doi: 10.1016/j.jconrel.2018.02.025. 
 
44: Ortalli M, Ilari A, Colotti G, De Ionna I, Battista T, Bisi A, Gobbi S, Rampa A, Di  
Martino RMC, Gentilomi GA, Varani S, Belluti F
“Identification of chalcone-based antileishmanial agents targeting trypanothione reductase”
European journal of medicinal chemistry 152, 527-541. doi: 10.1016/j.ejmech.2018.04.057.
 
45. Ilari A, Genovese I, Fiorillo F, Battista T, De Ionna I, Fiorillo A, Colotti G*. 
“Toward a Drug Against All Kinetoplastids: From LeishBox to Specific and Potent
Trypanothione Reductase Inhibitors.” 
Mol Pharm. 2018 Jun 27. doi: 10.1021/acs.molpharmaceut.8b00185.
 
46. Genovese I, Ilari A, Battista T, Chiarini V, Fazi F, Fiorillo A, Colotti G.*
 “Molecular bases of Sorcin-dependent resistance to chemotherapeutic agents”
 Cancer Drug Resist. 2018; 1:164-180. doi:10.20517/cdr.2018.10.
 
47. Kahremany S, Zhenin M, Shenberger Y, Maimoun D, Colotti G, Arad M, Shainberg
 A, Senderowitz H, Ruthstein S, Gruzman A.
 “Peptide-based development of PKA inhibitors”
 New Journal of Chemistry 2018, 42, 23:18585-18597. doi: 10.1039/C8NJ01732H.
 
48. Turcano L, Torrente E, Missineo A, Andreini M, Gramiccia M, Di Muccio T, Genovese
    I, Fiorillo A, Harper S, Bresciani A, Colotti G*, Ilari A.
“Identification and binding mode of a novel Leishmania Trypanothione reductase
inhibitor from high throughput screening”
PLOS Neglected Tropical Diseases 2018, 12,11:e0006969.
doi:10.1371/journal.pntd.0006969
 
49. Pippa S, Mannironi C, Licursi V, Bombardi L, Colotti G, Cundari E, Mollica A,  
Coluccia A, Naccarato V, La Regina G, Silvestri R, Negri R.
 “Small Molecule Inhibitors of KDM5 Histone Demethylases Increase the 
Radiosensitivity of Breast Cancer Cells Overexpressing JARID1B”
 Molecules 2019, 1, 9:1739. doi:10.3390/molecules24091739.
 
50. Chiarini V, Tossavainen H, Sharma V, Colotti G*.
 “NMR structure of a non-conjugatable, ADP-ribosylation associated, ubiquitin-like 
domain from Tetrahymena thermophila polyubiquitin locus”
 Biochimica et Biophysica Acta (BBA)-General Subjects 2019, 1863, 4:749. doi: 
10.1016/j.bbagen.2019.01.014.
 
51. Colotti G*, Saccoliti F, Gramiccia M, Di Muccio T, Prakash J, Yadav S, Kumar Dubey
V, Vistoli G, Battista T, Mocci S, Fiorillo A, Bibi A, Madia VN, Messore A, Costi R, Di Santo R, Ilari A.
 “Structure-guided approach to identify a novel class of anti-leishmaniasis diaryl 
sulfide compounds targeting the trypanothione metabolism”
 Amino Acids 2019, 1-13. doi: 10.1007/s00726-019-02731-4.
 
52. Rinaldi T, Colotti G*.
 “Use of organoids in medicinal chemistry: challenges on ethics and biosecurity”
 Future Medicinal Chemistry 2019, 11 (10), 1087-1090. doi: 
10.4155/fmc-2018-0341.
 
73. Carbo M, Brandi V, Pascarella G, Staid DS, Colotti G, Polticelli F, Ilari A, Morea V.
 “Bioinformatics analysis of Ras homologue enriched in the striatum, a potential target for Huntington's disease therapy”
 International journal of molecular medicine 2019, 4373. doi: 
10.3892/ijmm.2019.4373.
 
*: corresponding author

 

Dr. Andrea Ilari
Dr. Pierpaolo Ceci
Dr. Adele Di Matteo
Dr. Alessandro Giuffré
Dr. Veronica Morea
Dr. Carmelinda Savino
Dr. Annarita Fiorillo
Dr. Ilaria Genovese
Dr. Theo Battista

Prof. Godfrey L. Smith, University of Glasgow (Scotland, UK)
Dr. Vasiliki Lalioti, CSIC; Universidad Autonoma, Madrid (Spain)
Dr. David O’Connell, University College of Dublin (Ireland) 
Prof. Giulia d'Amati, Sapienza University, Rome (Italy)
Dr. Francesco Fazi, Sapienza University, Rome (Italy)
Prof. Ylva Ivarsson, Uppsala University, Uppsala (Sweden)

DEGREES: 

1989: degree in Biological Sciences (with honors), University of Rome "La Sapienza", Italy.
1993: Ph.D. in Biochemistry

PROFESSIONAL EXPERIENCE:

1990-1993: Ph. D. Dept. Biochemical Sciences, University Sapienza, Rome, Italy
1991-1993:  Program in Molecular Medicine and Department of Biochemistry and Molecular Biology, University of Massachusetts Medical Center, Worcester, Massachusetts.
1993-1994: CNR fellowship in Molecular Biology and Biotechnology
1994-1995: Post-doc fellowship in Medical Sciences, Faculty of Medicine, University of Rome "La Sapienza".
1996-present: Research Scientist at the Institute of Molecular Biology and Pathology, CNR (National Research Council).
2009: idoneity First Research Scientist, Physical Sciences, CNR.
2010: idoneity First Research Scientist, Life Sciences, CNR.
2014: idoneity Associate Professor (National Scientific Abilitation, 05-E2 Molecular Biology)
2017: idoneity Associate Professor (National Scientific Abilitation, 05-E1 Biochemistry)
2017: idoneity Full Professor (National Scientific Abilitation, 05-E1 Biochemistry)


TEACHING

1997-2010: Course of Molecular Biology, School of Specialization in Pathological Anatomy, Faculty of Medicine, University "Sapienza", Rome, Italy.
1997-2010: lecturer of Molecular Biology, First School of Specialization in Oncology, Faculty of Medicine, University "Sapienza", Rome, Italy.
2005: Course "Applications of Bioinformatics in Molecular and Structural Biology" Institute of Molecular Biology and Pathology, CNR.
2005: Course "Bioinformatics for Molecular and Cellular Biologists", Ph.D. in Cellular Biology, University "Sapienza", Rome, Italy.
2007: Course "Bioinformatics for Biologists", CNR.
2010: Course "Bioinformatics for Molecular Biologists", CNR. 
2011: Lecturer of the Course "Bioinformatics for biology", University L'Aquila, Italy
Since 2017: member of the Teaching Board, Ph.D. School of Biochemistry, Sapienza University, Rome


RECENT RESEARCH PROJECTS:

Italian Substitute, COST (European Cooperation in Science and Technology) Harmonizing standardisation strategies to increase efficiency and competitiveness of European life-science research (CHARME).
Coordinator of Work Package (WP2): Flagship Project Nanomax: “Nanotechnology-based Diagnostics In Neurological diseases and Experimental oncology” Acronym: “NADINE” Scientific Coordinator Prof. A. Boffi.
Coordinator of the project: “Molecular complexes of sorcin and E-Syt1 in the generation and regulation of calcium-dependent cellular functions”, CNR-CSIC 2010-2012.
Coordinator of Operative Unit, Project "Pemphigus vulgaris as a paradigm of autoantibody-mediated organ-specific autoimmune disorder: pathophysiology and novel tools for diagnosis and therapy", RF-2010-2309790, 2012-2016.
Coordinator of the Task: “Quality methods for Design of Experiments in Scientific Research”, qPMO CNR 2012-2015.
Scientific Coordinator of operative Unit, PRIN (Research Programs of National Interest) Project 2007 “Supramolecular complexes of sorcin in the generation and regulation of Calcium-dependent cellular functions”, 2008-2011.
Coordinator of the project "A new penta-EF protein in yeast: YGR058W. A possible role in the regulation of cell duplication", CNR.

 

ACTIVITIES

Since 2009: Member of NetwOrK, the Network for Outreach and Knowledge CNR
Since 2010: Coordinator for Technology Transfer for IBPM CNR.
Since 2010: Expert in the regional plan for experimental action for the innovation in technical formation. 
Since 2012: Co-founder and member of the Foresight Group CNR, a resource for making future scientific and technological choices for the CNR.
Since 2012: Co-founder of the qPMO (Quality and Project Management OpenLab) CNR.