Study o of structure-function relationship in proteins  mainly by the X-ray crystallography with the aim to find new inhibitors of the studied enzymes to be used as lead compound for drug design.

Andrea Ilari obtained the structures by X-ray crystallography of different proteins:

1)E. coli flavohemoglobin and of the following truncated hemoglobins: Bacillus subtilis truncated hemoglobin  and Thermobifida fusca truncated hemoglobin. The structural analyses disclosed the role of these protein in the protection mechanism of bacteria from oxidative damage.

2)Sorcin  (SOluble Resistance related Calcium bInding proteiN) a protein involved in excitation-contraction-relaxation processes in the heart through the interaction with several Ca2+ channels.

3) Studies of the molecular mechanism of MuntiDrug Resistance in cancer cell involving Sorcin.

3)Dps (DNA binding proteins from starved cells)  cage-like proteins involved in the bacterial-DNA protection from oxidative damage and used as bioreactor to produce metal-based nanoparticles. 

4)Structure of the proteins involved in the trypanothione metabolism, a molecule which protect the Leishmania parasites (responsible for Leishmaniasis) from the ROS (Reactive Oxygen Species) produced by macrophages during the infection . 

5)ZnuA, the periplasmic component of the bacterial zinc transporter ZnuABC.  The study aims at designing a new antibiotic against Salmonella enterica which, as all the gram negative bacteria, develops very easily drug resistance. 

6) Identification of molecular markers of Huntington Disease a neurodegenerative disease due to a mutation in the Huntingtin gene.

1:Genovese I, Giamogante F, Barazzuol L, Battista T, Fiorillo A, Vicario M, D'Alessandro G, Cipriani R, Limatola C, Rossi D, Sorrentino V, Poser E, Mosca L, Squitieri F, Perluigi M, Arena A, van Petegem F, Tito C, Fazi F, Giorgi C, Calì T, Ilari A, Colotti G. Sorcin is an early marker of neurodegeneration,
Ca²⁺ dysregulation and endoplasmic reticulum stress associated to neurodegenerative diseases. Cell Death Dis. 2020 Oct 15;11(10):861. 
2: Turcano, L; Battista, T; De Haro ; Missineo, A; Alli, C ; Paonessa, G; Colotti, G; Harper, S; Fiorillo, A; Ilari, A; Bresciani, A Spiro-containing derivatives show antiparasitic activity against Trypanosoma brucei through inhibition of the trypanothione reductase enzyme PLOS NEGLECTED TROPICAL DISEASES 2020, 14(5), e0008339
3: 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.
4: Kasyutich O, Ilari A, Fiorillo A, Tatchev D, Hoell A, Ceci P. Silver ion incorporation and nanoparticle formation inside the cavity of Pyrococcus furiosus ferritin: structural and size-distribution analyses. J. Am. Chem. Soc., 2010, 132(10):3621-7. 
5: Baiocco P, Colotti G, Franceschini S, Ilari A. “Molecular basis of antimony treatment in leishmaniasis.” J Med Chem., 2009; 52(8):2603-12. 
6: Ilari A, Franceschini S, Bonamore A, Arenghi F, Botta B, Macone A, Pasquo A, Bellucci L, Boffi A. “Structural basis of enzymatic (S)-norcoclaurine biosynthesis.” J Biol Chem. 2009; 284(2):897-904.  
7: Ilari A., Ceci P., Ferrari D., Rossi G.L., Chiancone E.,”Iron incorporation into Escherichia coli Dps gives rise to a ferritin-like microcrystalline core” J. Biol. Chem.,277, 37619-23, (2003).
8: Ceci P.,  Ilari A.,  Falvo E.,  Chiancone E., “The Dps protein of Agrobacterium tumefaciens does not bind to DNA but protects it toward oxidative cleavage: X-ray crystal structure, iron binding, and hydroxyl-radical scavenging properties.”J. Biol. Chem., 278, 20319-26, (2003). 
9: Zhao G., Ceci P., Ilari A., Giangiacomo L., Laue T.M., Chiancone E., Chasteen N.D. “Iron and hydrogen peroxide detoxification properties of DNA-binding protein from  starved cells. A ferritin-like DNA-binding protein of Escherichia coli.” J Biol Chem. 2002; 277(31):27689-96.
10: Ilari A., Bonamore A., Farina A., Johnson .K. A., Boffi A., “ The X-ray structure of E. Coli flavohemoglobin reveals an unexpected geometry of the distal heme pocket.”, J. Biol. Chem., 277, 23725-32, (2002).
11: Ilari A., Johnson K. A., Nastopoulos V., Verzili D., Zamparelli C., Colotti G.,Tsernoglou D. and Chiancone E., “The crystal structure of the sorcin calcium binding domain provides a model of Ca2+-dependent processes in the full-length protein”, J. Mol. Biol., 317, 447-458, (2002).
12: Ilari, A., Stefanini, S., Tsernoglou, D., and Chiancone E., “ The dodecameric ferritin from L. innocua contains a novel intersubunit iron-binding site”, Nature Struct. Biol., 7, 38-43,  (2000).

Annarita Fiorillo, Postdoc, Dip. Scienze Biochimiche Università Sapienza

Paola Baiocco, Postdoc, Dip. Scienze Biochimiche Università Sapienza

Dott. Ferdinando Squitieri, Casa Sollievo della Sofferenza e CSS-Mendel

Prof.ssa Emilia Chiancone, Prof. emerito, Dip. Scienze Biochimiche

Prof. Alberto Boffi, Dip. Scienze Biochimiche, associato IBPM

Prof. ssa Beatrice Vallone, Dip. Scienze Biochimiche, associato IBPM

Dottoressa Marina Gramiccia, Istituto Superiore di Sanità

Dott. Marco Lalle, Istituto Superiore di Sanità

Dott. Luca Vannucci, Institute of Microbiology Academy of Sciences Czech Repubblic

Dott. Vassiliki Lalioti, CSIC, Madrid, Spain

EDUCATION

1998 - Ph.D. in Biophysics at the University of Roma  “La Sapienza”. Dissertation:”Metal binding proteins: (a) "Sorcin (SOlubile Resistance related Calcium-bInding proteiN), a penta-EF calcium binding protein with a role in the calcium-mediated intracellular signal transduction"; (b) "Crystallization and preliminary X-ray diffraction studies on the ferritin from  Listeria innocua"

1997- Research training in “Crystallization of hemoproteins in presence and absence of oxygen”, Prof. W. E. Royer, Medical Center, University of Massachusetts, Worcester, USA.. 

1993 - Laurea in Chemistry, summa cum laude, at the University of Roma “La Sapienza”. Thesis :” "Heme- protein interactions in the Horse spleen Myoglobin and in the homodimeric hemoglobin from Scapharca inaequivalvis. Fluorescence and optical absorption studies on the proteins reconstituted with Zn- e Protoporfirin IX";

in 1987: High school Diploma,  Liceo Scientifico Statale "C. Cavour" of Roma.

PROFESSIONAL EXPERIENCE:

Since January 1th 2007: first researcher at the “Istituto di Biologia e Patologia Molecolari”, Centro Nazionale delle Ricerche (Italian Research National Council).

2001-2007 : Research fellow at the “Istituto di Biologia e Patologia Molecolari”, Centro Nazionale delle Ricerche (Italian Research National Council).

1999-2001  Research fellowship: “Crystallization of macromolecules in microgravity”, at the “Istituto di Biologia e Patologia Molecolari”, Centro Nazionale delle Ricerche (Italian National Research Council) in collaboration with the ASI (Italian Space Agency) (projects ASI/ARS-99-22, ASI/I/R/28/00)

1999 –Research fellowship : “Structural dynamics of nitrite reductase”. In collaboration with the “Centre National de la Recherche scientifique”- Laboratoire de Cristallographie et Cristallisation des Macromolécules Biologiques – Marseille (France) on the project .

1998 –Post-doctoral fellowship: “Research on resistance-related proteins of Mycobacteria”, Dep. of Genetics and Microbiology ,University of Pavia, Italy.

TEACHING ACTIVITY

2014-2020 From 2014 is a member of the committee of the Ph.D. in Biochemistry of the Department of biochemical Sciences of the Sapienza  University of Roma. 

2011 – Lecturer of the Practical Course “Bioinformatic Applications in  Structural and Molecular Biology” organized for the Ph.D student in Biochemistry of the Department of Biochemical Sciences , University of L’Aquila.

2010 – 19/10-4/11. : Lecturer of the Practical Course “Bioinformatic Applications in  Structural and Molecular Biology” for the personnel of the Institute of Molecular Biology and Pathology, CNR. 

2002-2010: Lecturer of the Course of stoichiometric calculations  for undergraduate students, laurea in “Tecnico di Laboratorio Biomedico”,  Medicine and Surgery Faculty, University of Roma “La Sapienza” 

2002-2010:Lecturer of the Course of stoichiometrical calculations  for undergraduate students, laurea in Medicine and Surgery Faculty, University of Roma “La Sapienza” . 

2007: Lecturer of the Practical Course “From the protein crystallization to the protein structure determination”, for the personnel of the Institute of Molecular Biology and Pathology, CNR.

RESEARCH PROJECTS PI (Last 5 years)

2018-present: Project on HD (acronym: RARE in rarity) funded by the Italian Ministry of Health, Grant number RF 2016-02364123” (Head of Research Unit)

2015-present: Project title: “Structural and functional studies on trypanothione and polyamines metabolism enzymes”, funded by CONSORZIO CNCCS (Principal Investigator)

SCIENTIFIC CONFERENCE ORGANIZATION

2019 -Naples4-7 sptember –member of the scientific commettee  of the congress MISCA V.  Fifth Meeting of the Italian (AIC) and Spanish Crystallographic (GE3C) Associations 

2019 – 10-11 october, CNR, Rome member of the scientific commettee of the congress “Cryo-electron microscopy in structural biology: paving the way towards precision biomedicine and biotechnology” 

2019 -9 may   member of the scientific commettee of the congress  IBPM-CNR “From model systems to therapies”.

2018 – 8/5/2018  member of the scientific commettee of the congress  IBPM-CNR “Health, disease and environmental research: biology, tools and applications”.

2018- Rome 25-28 June- member of the scientific and organizing commettees  of the congress  “3rd Joint AIC-SILS conference”. 

2014 –Turin, 16-17 october , member of the scientific commettee of the congress: "Crystal (Cl)year" 

1999 – Andrea Ilari was in the organization commettee of the congress “Biocrystallography for Medicine and Biotechnology” Roma - Auditorio dell’Accademia Nazionale dei Lincei.

INVITED LECTURES (last 5 years)

2020- 10 february. Invited speaker  at the congress  “Structural Biology Italian Network: Instruct-ITALIA”

2018 -26-28 november Rome- Invited speaker at the World Structural and Molecular Conference, with tge following seminar: “Structure-Based Drug Design On Trypanothione Reductase To Find New Drugs Against Leishmaniasis”.

2018- 2-7 september Ocean University and Howard Civil Service International House, Taipei (Taiwan) Invited speaker  at the congress “Fifth International Conference on Polyamines: Biochemical, Physiological and Clinical Perspectives” with the following talk: “Enzymes of the trypanothione-based redox metabolism and anti-kinetoplastid drug discovery."

2018 – 8 may 2018  invited speaker at the congress IBPM-CNR “Health, disease and environmental research: biology, tools and applications.”  with the following talk: “Protein crystallography at IBPM: function discovery of cage-like proteins and sorcin”.

2015  – 6-7 december, Indian Institute of Technology, Guwahati invited speaker at the congress:“Recent developments in Medicinal Biotechnology and Structure-based drug designing”,  Trypanothione reductase and Trypanothione peroxidase, key enzymes of Leishmania dithiol redox metabolism: structural, functional and inhibition studies on the enzymes of the trypanothione metabolism.

PROGRAM CHAIR:

2019 -  10-11 october, chairman at the congress “Cryo-electron microscopy in structural biology: paving the way towards precision biomedicine and biotechnology” at the  session: "CryoEM and biomedicine Part II."

2015- 6-7 december IIT, Guwahati, India,  chairman at the congress “Recent developments in Medicinal Biotechnology and Structure-based drug designing”  .

2009- Session of “Microbiology” del 12th International Symposium on Molecular Medicine, Hotel Poseidon Resort, Loutraki, Greece, 15-17 October.

SCIENTIFIC AWARDS

2009-  Scientific award from the CNR President Luciano Maiani for the innovative results in research, reached in 2005.

PUBLICATIONS

• 86 total, 23 as first, 27 as last or corresponding Author
• H-index = 29 (SCOPUS)

2012- Editorial member of Journal of Biological Research (ISSN 2225-3203)

PATENT

Piera Valenti, Tiziana Natalizi, Roberto Di Santo, Luca Pescatori Giuliana Cuzzucoli Crucitti, Emilia Chiancone, Andrea Ilari: Pirrolil-idrossammati per uso nella prevenzione e/o nel trattamento di infezioni batteriche. Depositato il 6 giugno 2012 al numero MI2012A000980.

BOOKS CHAPTERS

2018 - Colotti G., Ilari A. Sorcin Encyclopedia of signaling Molecules, Second edition, Sangdun Choi edition, Pages 5084-5093

2017- Ilari A, Savino C. A Practical Approach to Protein Crystallography. Methods Mol Biol. 1525:47-78. 

2015 -A. Ilari, A. Bonamore, and A. Boffi  « Addition to C=N Bonds”, Book title: “Biocatalysis in Organic Synthesis 2”, Science of Synthesis (SOS) 2014-2016, Editor Thieme Chemistry.

2011- Pierpaolo Ceci, Veronica Morea, Manuela Fornara, Giuliano Bellapadrona, Elisabetta Falvo and Andrea Ilari “Biomimetic materials synthesis by ferritin-related, cage-shaped proteins”, Book title “Biomineralization”, 2011, Editor Intech - Open Access Publisher.

2009 -Stefanini S., Ceci P., Ardini M., Ilari A.: DNA-binding proteins from sterved cells, Handbook of metalloproteins, edited by Prof. Messerschmidt, John Wiley & Sons, Ltd.

2008- Ilari A, Savino C. “Protein structure determination by X-ray crystallography.”  Book title: “Bioinformatics: Data, Sequence Analysis and Evolution”, Editor Jonathan M. Keith, Series: Methods in Molecular Biology, Volume 452, pages 63-87.