Maurizio Cirilli


Monterotondo Scalo – Campus “A.Buzzati Traverso”
maurizio.cirilli@cnr.it

My research activity focus on the discovering the molecular details of how cellular biomolecular complexes and networks works by analyzing protein-protein interfaces of 3D structures. Most of the biological processes are carried out by macromolecular assemblies and regulated through a complex network of protein-protein interactions that define the homeostatic state of the cell. So, the study of these interactions is pivotal in both health and disease and it is tied to the knowledge of the 3D atomic structure of the interacting partners of their complexes. With this aim, I use the X-ray diffraction analysis on single crystal as primary methodology to study proteins and protein complexes engaged in important cellular functions. Both de novo and derived from homologous structures methods for estimation of phases are used.

Despite advances in experimental methods of structure determination and the enormous amount of data obtained by deep genomic sequencing, the number of known protein interactions are by far lagging behind. For this reason, I am moving more and more toward the application of computational methodologies of structure prediction of single proteins and complexes as valuable tools to complement my experimental research.

With the promise to overcame all the drawbacks of the experimental structural determination in terms of time, money and high-throughput capacity, computational biology has made great strides toward being a mature and lively field of research. Computational structural biology can be harnessed to reveal the mechanisms of mutations and signaling specificity by combining powerful algorithms with experimental data from various sources and to generate reliable models of single proteins and protein complexes.

Education:

December 1984
Laurea Biological Sciences University “La Sapienza” di Roma

Positions:

December 1988 – May 2011
Researcher at Institute of Structural Chemistry, CNR– Montelibretti (Rome)

February 1997 – August 1999
Associate Researcher at the Biochemistry Department of Albert Einstein College of Medicine-Yeshiva University, New York (USA)

September 1999 – August 2002
Associate Researcher at the Biochemistry Department of Weill Medical College-Cornell University, New York (USA)

May 2011 – now
Researcher at Institute of Biochemistry, Cell Biology and Neurobiology (IBBC), CNR – Monterotondo (Rome)

Patents

POLITI V., GAVUZZO E., GALLINA C., DI STAZIO G., D’ALESSIO S., SELLA A., PIAZZA C., GIORDANO C., GORINI B., PANINI G., PAGLIALUNGA PARADISI M., CIRILLI M., POCHETTI G., MAZZA F.
“Nuovi inibitori di metalloproteinasi, loro uso terapeutico e procedimento per la produzione del composto di partenza nella loro sintesi”.
Brevetto n° RM97A0441, 1997.

POLITI V., GAVUZZO E., GALLINA C., DI STAZIO G., D’ALESSIO S., SELLA A., PIAZZA C., GIORDANO C., GORINI B., PANINI G., PAGLIALUNGA PARADISI M., CIRILLI M., POCHETTI G., MAZZA F.
“Preparation of Phosphotryptophanyl Peptides, Metalloproteinase Inhibitors”.
Patent: PCT Int. Appl. WO 99 03,878 (Cl. C07k5/00),
28 Jan. 1999, Appl. 97/RM441, 17 Jul 1997, 40 pp. (Eng). 

POLITI V., GAVUZZO E., GALLINA C., DI STAZIO G., D’ALESSIO S., SELLA A., PIAZZA C., GIORDANO C., GORINI B., PANINI G., PAGLIALUNGA PARADISI M., CIRILLI M., POCHETTI G., MAZZA F. ” Inhibitors of Metalloproteinase, their Therapeutic Use, and Process for the Production of the Starting Compound in the Synthesis”.
Patent No. 98932516, 30 Mar. 2000. 

POLITI V., GAVUZZO E., GALLINA C., DI STAZIO G., D’ALESSIO S., SELLA A., PIAZZA C., GIORDANO C., GORINI B., PANINI G., PAGLIALUNGA PARADISI M., CIRILLI M., POCHETTI G., MAZZA F. “Metalloproteinase Inhibitors, their Therapeutic Use and Process for the Production of the Starting Compound in the Synthesis Thereof”.
Patent No. US 6,339,160 B1, 15 Jan. 2002. 

POLITI V., GAVUZZO E., GALLINA C., DI STAZIO G., D’ALESSIO S., SELLA A., PIAZZA C., GIORDANO C., GORINI B., PANINI G., PAGLIALUNGA PARADISI M., CIRILLI M., POCHETTI G., MAZZA F.
” Inhibitors of Metalloproteinase, their Therapeutic Use, and Process for the Production of the Starting Compound in the Synthesis”.
European Patent n. EP 1019434, 1 Oct. 2003.

 

LUSTBADER J, CIRILLI M., LIN C., XU H.W., CASPERSEN C., WANG N.,   TAKUMA K., CHEN X., CHANEY M. TRINCHESE F., LIU S., KUPPUSAMY P., ZEWIER Z., ARANCIO O., STERN D., YAN S.D., WU H.
Science (2004) 304, 448-52

XU G., CIRILLI M., HUANG Y., RICH R.L., MYSZKA D.G., WU H.
Nature. (2001) v.410 , 494-7

YE H., ARRON J.R., LAMOTHE B., CIRILLI M., KOBAYASHI T., SHEVDE N.K., SEGAL D., DZIVENU O.K., VOLOGODSKAYA M., YIM M., DU K., SINGH S., PIKE J.W., DARNAY B.G., CHOI Y., WU H.
Nature. (2002) v 418, 443-7

CIRILLI M., ZHENG R., SCAPIN G., BLANCHARD J.S.
Biochemistry (1998) v.37, 16452-16458

CIRILLI M., GALLINA C., GAVUZZO E., GIORDANO C., GOMIS-RUTH F.X.,GORINI B., KRESS L.F., MAZZA F., PAGLIALUNGA PARADISI M., POCHETTI G., POLITI V.
FEBS Letters (1997) v.418, 319-322

View all pubblications

  • CIRILLI M., GIOMINI M., GIULIANI A.M., TROTTA E.
    “ A Truncated Driven Overhauser Effect Study of Adriamycin in Water: Conformation of the Glycosidic Linkage “ Spectrochimica Acta (1991) v. 47a , 759-764.
  • TROTTA E., D’AMBROSIO E., DEL GROSSO N., RAVAGNAN G., CIRILLI M., PACI M.
    “ 1H NMR Study of [d(GCGATCGC)]2 and its Interaction with Minor Groove Binding 4′,6-Diamidino-2-Phenylindole “ Biol. Chem. (1993) v. 268, 3944-3951.
  • CIRILLI M., BACHECHI F., UGHETTO G., COLONNA F.P., CAPOBIANCO M.L.
    “ Interactions Between Morpholinyl Antracyclines and DNA. The Crystal Structure of a Morpholino Doxorubicin bound to d(CGTACG) “ Mol. Biol. (1993) v. 230, 878-889.
  • CASARINI D., LUNAZZI L., GASPARRINI F., VILLANI C., CIRILLI M., GAVUZZO E.“ Conformational Assignment, Absolute Configuration, and Chiral Separation of All the Stereoisomers Created by the Combined Presence of Stereogenic Centers and Stereogenic Conformational Axes in a Highly Hindered 1,5-Naphthyl Sulfoxide “Org. Chem. (1995) v. 60, 97-102.
  • ALTOMARE C., CELLAMARE S., CAROTTI A., BARRECA M.L., CHIMIRRIA., MONFORTE A.M., GASPARRINI F., VILLANI C., CIRILLI M., MAZZA F.
    “ Substituent Effects on the Enantioselective Retention of Anti-HIV 5-Aryl- 2-1,2,4-Oxadiazolines on R,R-DACH-DNB Chiral Stationary Phase “ Chirality (1996) v. 8, 556-566.
  • CIRILLI M., GALLINA C., GAVUZZO E., GIORDANO C., GOMIS-RUTH F.X.,GORINI B., KRESS L.F., MAZZA F., PAGLIALUNGA PARADISI M., POCHETTI G., POLITI V.
    “ 2 Å X-Ray Structure of Adamalysin II Complexed with a Peptide Phosphonate Inhibitor Adopting a Retro-Binding Mode “ Febs Letters (1997) v. 418, 319-322.
  • CIRILLI R., GAPARRINI F., VILLANI C., GAVUZZO E., CIRILLI M.
    “ The Chiral Selector N-(2′-S-Hydroxypropyl)-N,N’-bis (3,5-Dichlorobenzoyl)-1R,2R-Diaminocyclohexane “ Acta Cryst. (1997) v. C53, 1937-1939.
  • SCAPIN G., CIRILLI M., REDDY S.G., GAO Y., VEDERAS J.C., BLANCHARD J.S. “Substrate and Inhibitor Binding Sites in Corynebacterium Glutamicum Diaminopimelate Dehydrogenase” Biochemistry (1998) v. 37, 3278-3285.
  • CIRILLI M., GAVUZZO E., GIORDANO C., GORINI B.
  • “ Crystal Structure of Diethyl-1-Hydroxyimine-2- (3-Indolyl)-Ethan-Phosphonate Monohydrate, C14H21N2O5P.H2O “ Zeitschrift fur Kristallographie (1998) v. 213, 125-126.
  • CIRILLI M. “ Crystal Structure of N-Benzoyl-L-Alanyl-N-Phenyl-L- Alaninamide, C19H21N3O3 “ Zeitschrift fur Kristallographie (1998) v.213, 127-128.
  • CIRILLI M., COIRO V.M., DI NOLA A., MAZZA F. “ Relationship Between Conformation and Geometry as Evidenced by Molecular Dynamics Simulation of Calfa,alfa-Dialkylated Glycines “ Biopolymers, (1998) v. 46, 239-244.
  • ETTORRE A., CIRILLI M., UGHETTO G. “ Degradation of the Morpholino Ring in the Crystal Structure of Cyanomorpholinodoxorubicin Complexed with d(CGATCG) “
    Eur. J. Biochem., (1998) v. 258 , 350-354.
  • CIRILLI M., ZHENG R., SCAPIN G., BLANCHARD J.S. “Structural Symmetry: The Three-Dimensional Structure of Haemophilus influenzae Diaminopimelate Epimerase “Biochemistry (1998) v. 37, 16452-16458.
  • CIRILLI R., GASPARRINI F., VILLANI C., GAVUZZO E., CIRILLI M. “The beta-adrenergic antagonist (S)-3-(1-Methylethyl)-5- [(1-naphthalenyloxy)methyl]-2-oxazolidinone “Zeitschrift fur Kristallographie (1999) v.214, 113-115.
  • CIRILLI M., SCAPIN G., SUTHERLAND A., VEDERAS JC., BLANCHARD J.S..
    “The three-dimensional structure of the ternary complex of Corynebacterium       glutamicum diaminopimelate dehydrogenase-NADPH-L-2-amino-6’methylene-pimelate” Protein Sci. (2000) v (10) , 2034-7.           
  • XU G., CIRILLI M., HUANG Y., RICH R.L., MYSZKA D.G., WU H. “Covalent inhibition revealed by the crystal structure of the caspase8/p35 complex.” Nature. (2001) v 410 , 494-7
  • YE H., ARRON J.R., LAMOTHE B., CIRILLI M., KOBAYASHI T., SHEVDE N.K., SEGAL D., DZIVENU O.K., VOLOGODSKAYA M., YIM M., DU K., SINGH S., PIKE J.W., DARNAY B.G., CHOI Y., WU H. “Distinct molecular mechanism for initiating TRAF6 signalling”
    Nature. (2002) v 418, 443-7.
  • YE H., CIRILLI M., WU H “The use of construct variation and diffraction data analysis in the crystallization of the TRAF domain of human tumor necrosis factor receptor associated factor 6” Acta Cryst. (2002). D58, 1886-1888
  • CIRILLI M., ZHENG R., SCAPIN G., BLANCHARD J.S. “The three-dimensional structures of the Mycobacterium tuberculosis dihydrodipicolinate reductase-NADH-2,6-PDC and -NADPH-2,6-PDC complexes. Structural and mutagenic analysis of relaxed nucleotide specificity” (2003). 42, 10644-50
  • LUSTBADER J, CIRILLI M., LIN C., XU H.W., CASPERSEN C., WANG N.,   TAKUMA K., CHEN X., CHANEY M. TRINCHESE F., LIU S., KUPPUSAMY P., ZEWIER Z., ARANCIO O., STERN D., YAN S.D., WU H. “Alzheimer’s disease and mitochondria: structural and functional consequences of Aβ interaction with ABAD” Science (2004) 304, 448-52
  • TEMPERINI C, CIRILLI M, ASCHI M, UGHETTO G “Role of the amino sugar in the DNA binding of disaccharide anthracyclines: crystal structure of the complex MAR70/d(CGATCG).” Bioorg Med Chem. (2005) 13, 1673-9.
  • CIRILLI M., BERESHCHENKO O., ERMAKOVA O., NERLOV C. “Insights into specificity, redundancy and new cellular functions of C/EBPa and C/EBPb transcription factors through interactome network analysis” Biochim Biophys Acta Gen Subj. (2017) 1861(2), 467-476
  • CHIANI F., ORSINI T., GAMBADORO A., PASQUINI M., PUTTI S., CIRILLI M., ERMAKOVA O., TOCCHINI-VALENTINI G.P. “Functional loss of Ccdc151 leads to hydrocephalus in a mouse model of primary ciliary dyskinesia” Dis Model Mech. (2019) 12(8), 1-13