Institute of Crystallography - CNR
Senior Researcher

Milardi Danilo



from 2021 – ongoing Senior Researcher
Institute of Crystallography, National Research Council, Italy

Business or sector EPR

from 2021 – ongoing Lecturer
International Doctorate School of Chemical Sciences, Department of Chemical sciences, University of Catania
▪ Front lessons
Business or sector : University

from 2019 to 2020 Researcher
Institute of Crystallography, National Research Council, Italy

Business or sector EPR

from 2001 to 2019 Researcher
Institute of Biostructures and Bioimages, National Research Council, Italy.

Business or sector : EPR

from 1999 to 2001 Post-doc fellow
Department of Chemical Sciences, University of Catania, Catania, Italy.

Business or sector : University

from 1997 to 1999 Research fellow
Wyeth Lederle, Catania Plant, Italy

Business or sector : Enterprise

from 1996 to 1997 Research collaborator
Department of Chemical Sciences, University of Catania, Catania, Italy.

Business or sector : University


from 1993- to 1996 PhD in Chemical Sciences
Dipartimento di Scienze Chimiche, Università di Catania, Catania, Italy

Replace with dates (from – to) Graduate degree in Industrial Chemistry

Dipartimento di Scienze Chimiche, Università di Catania, Catania, Italy


Awards 2016 He has the National Italian Habilitation to Full Professor, in the area 03/B1 “Fondamenti delle Scienze Chimiche e Sistemi Inorganici”
2016 He has the National Italian Habilitation to Full Professor, in the area concorsuale 03/A2 “Modelli e metodologie per le scienze Chimiche”
2016 He has the National Italian Habilitation to Full Professor, in the area 03/B2 “Fondamenti chimici delle tecnologie”.

Editorial activity 2021 Member of the Editorial Board of the Journal “Biophysica” MDPI publisher
2014 Managing Guest Editor of the “Special Issue – Molecular Dynamics: New Advances in Drug Discovery” in: European Journal of Medicinal Chemistry, Elsevier.
2010 Editor of the book: Neurodegeneration: Metallostasis and Proteostasis, (Eds: D. Milardi and E. Rizzarelli), The Royal Society of Chemistry, Drug Discovery Series (UK) pubblicato nel 2010.

2001 – 2021

He is currently reviewer of the following journals: 1. European Journal of Medicinal Chemistry 2. Bioinorganic Chemistry and Applications, 3. Journal of Inorganic Biochemistry, 4. Biochimica Biophysica Acta – Proteins and Proteomics, 5. Biological Chemistry, 6. Metallomics, 7. ACS Chemical Neuroscience, 8. Peer J, 9. Cell Reports, 10. Biochimica Biophysica Acta – Biomembranes, 11. Computers in Biology and Medicine, 12. ACS Omega 13. Chemical Communications, 14, Scientific Reports
Major invited presentations Title: “Misfolding ed aggregazione delle proteine: Le basi chimiche della neuro degenerazione”. Hotel Capo Peloro Resort Messina, 26 Luglio 2013, Scuola Permanente per l’Aggiornamento degli Insegnanti di Scienze Sperimentali SPAIS 2103.
Title: “Aβ binds Ubiquitin and inhibits polyubiquitination: alternative mechanisms for amyloid toxicity, International Symposium on Pathomechanisms of Amyloid Diseases, December 20-21 (Thursday-Friday) 2018, Miami, Florida USA.
Title: “Repurposing pyrazolones as proteasome activators with neuroprotective activity, International Symposium on Pathomechanisms of Amyloid Diseases, December 18-20, 2019, Miami, Florida USA.
Title: “Proteostasis and Alzheimer’s Disease: a chemical approach” Conferenza di Dipartimento, 13-15 Dicembre 2021, CNR Roma.
Grants Role: Scientific Coordinator

He is local coordinator of the CNR Institute of Biostructures and Bioimages – Unit of Catania of the Project Miur-PRIN: Role of metal dyshomeostasis and ubiquitin-proteasome system derangement in brain pathologies: risk factors and neuroprotective strategies” – Prot. 20157WZM8A. budget: 56.000 euro.
He is coordinator of the project: “Design and synthesis of small molecules with neuroprotective and anticancer properties” in collaboration with the ONLUS AIPRAS (2020-2022).

Role: Partner
Participation as a partner (supervisor of an early stage young PhD student) to the EU project INCIPIT. COFUND Marie Skłodowska-Curie Actions GRANT AGREEMENT NUMBER — 665403 — INCIPIT. Total cost of the project 7.702.947.44 €.
PON Progetti di Ricerca Industriale e Sviluppo Sperimentale Specializzazione PNR 2015-2020 Innovative Devices For SHAping the RIsk of Diabetes (IDF SHARID).

Patents 1) Title: mixture of resveratrol derivatives for the chemoprevention and the treatment of protein conformational diseases. Application date: 13 July 2016. Application No.: 102016000073131, Italy.
2)Title: “DERIVATO BENZOMORFANICO ATTIVANTE I RECETTORI DELL’ADIPONECTINA IN SOGGETTI AFFETTI DA NEUROPATIA DIABETICA”. Inventori: GUCCIONE Salvatore, RONSISVALLE Simone, BASILE Livia, PAPPALARDO Matteo, SPADARO Angelo (Università di Catania); MILARDI Danilo (IC-CNR); NG Chun Laam (University of Hong Kong). Domanda brevetto in Italia, n° 102021000007730, presentata il 30/03/2021. Patent pending.

A major, broad goal of my research activity is to discover how intra- and inter-molecular interactions lead to the emergence of enzyme conformations and functions by combining calorimetric (DSC, ITC), spectroscopic (e.g. Circular Dichroism, UV adsorption or fluorescence emission) experiments with molecular dynamics. A major focus is to achieve new insights into functional molecular mechanisms regulating protein folding/assembly, with the ultimate goal of understanding how microscopic events may lead to eventually pathogenic consequences at a molecular level. In the last decade my research activity was devoted to issues related to protein folding, stability and aggregation. In addition, the role played by endogenous (e.g. pH, Metal ions and model membranes) or exogenous (small molecules) environmental factors in affecting protein misfolding was a special goal of my research activity. I have been also involved in many projects focusing of the design of drug candidates by virtual screening campaigns.

Some of my most relevant achievements in the field are: i) the discovery that porphyrins are tunable proteasome modulators; ii) the description of the role played by metal ions in the (mis)regulation of the Ubiquitin Proteasome pathway; iii) the adoption of calorimetric methods to describe the thermodynamics of miRNA sequences.


Prof. G. Canters, Gorleaus Laboratories, University of Leiden, The Netherlands.

Prof. Claudio Zannoni, Dipartimento di Chimica Industriale, Università di Bologna.

Prof. Imre Sovago, University of Debrecen, Hungary.

Prof. Amedeo Caflisch, Department of Biochemistry, University of Zurich, Switzerland

Prof. Gennaro Esposito, Dipartimento di Biochimica, Università di Udine.

Prof. Ayyalusamy Ramamoorthy, Department of Biochemistry, University of Michigan, USA.

Prof. Mikko Karttunen, University of Waterloo, Canada.

Prof. Michael Groll, University of Munchen, Germany.

Prof. Maria Gaczynska, University of San Antonio, Texas, USA

Prof. G. Melacini, Mc Master University, Canada,

Prof. Per Westermark, University of Uppsala, Sweden.

Prof. Ehud Gazit, University of Tel-Aviv, Israel.

Prof. Min Jan Lee, University of Seoul, South Korea.

Prof. Sheena Radford, University of Leeds, UK.

Prof. NG Chun Laam, University of Hong Kong.

Prof. Ashley Bush, University of Melbourne, Australia.

Heidelberg University Biochemistry Center, Heidelberg 69120, Germany

Department of Physics, University of Helsinki, Helsinki FI-00014, Finland.

Institute of Organic Chemistry and Biochemistry, Prague 160 00, Czech Republic.

Academy of Sciences of the Czech Republic, Prague 117 20, Czech Republic.

Department of Chemistry, University of Aarhus, Aarhus, Denmark.

Istituto Italiano di Tecnologia (IIT), Via Morego 30, 16163 Genoa, Italy

King’s College London, London SE1 1UL, UK

Institut National de la Recherche Agronomique, 78352 Jouy‑en‑Josas, France

Structural Biochemistry (ICS‑6), ForschungszentrumJülich, 52425 Jülich, Germany

North Carolina State University, Kannapolis, NC, USA

Molecular Genetics Laboratory UILDM, Santa Lucia Foundation, Rome, Italy.

The Ohio State University, Columbus, OH, 43210, USA.

Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France

Zoominar series: “Molecular Bases of Proteinopathies” (19/12/2022)
2022-ongoing: Panelist of the zoominar series
Molecular Bases of Proteinopathies
2020-2022 virtual meeting of talks and discussion on “protein multimerization: the good, bad, and exciting aspects”
The goal of this event is to bring scientific leaders working in the field of ‘Amyloid Research’ together from across the globe

Stretching the chains: the destabilizing impact of Cu2+ and Zn2+ ions on K48-linked diubiquitin

Mangini, Vincenzo; Grasso, Giulia; Belviso, Benny Danilo; Sciacca, Michele F. M.; Lanza, Valeria; Caliandro, Rocco; Milardi, Danilo

Dalton transactions (2003. Print) (2023)

Terpyridine Glycoconjugates and Their Metal Complexes: Antiproliferative Activity and Proteasome Inhibition

Panebianco, Roberta; Viale, Maurizio; Loiacono, Fabrizio; Lanza, Valeria; Milardi, Danilo; Vecchio, Graziella

ChemMedChem (Print) (2023)

The A?8-20 fragment as anti-fibrillogenic and neuroprotective agent: advancing towards efficient Alzheimer’s disease treatment

Stefania Zimbone, Maria Laura Giuffrida, Giuseppina Sabatino, Giuseppe Di Natale, Rita Tosto, Grazia M. L. Consoli, Danilo Milardi, Giuseppe Pappalardo, Michele F.M. Sciacca

ACS chemical neuroscience (2023)

Identification of a novel adiponectin receptor and opioid receptor dual acting agonist as a potential treatment for diabetic neuropathy

Ma O.K.-F.; Ronsisvalle S.; Basile L.; Xiang A.W.; Tomasella C.; Sipala F.; Pappalardo M.; Chan K.-H.; Milardi D.; Ng R.C.-L.; Guccione S.

Biomedicine & pharmacotherapy (2023)

Dipyridamole for tracking amyloidogenic proteins aggregation and enhancing polyubiquitination

Laneri, Francesca; García-Viñuales, Sara; Lanza, Valeria; Licciardello, Nadia; Milardi, Danilo; Sortino, Salvatore; Grasso, Giuseppe

Archives of biochemistry and biophysics (Print) (2022)

beta and gamma-Cyclodextrin dimers: design, characterization and in silico studies to explore the cooperative effect of the cavities

La Piana, Luana; Basile, Livia; Ragusa, Chiara; Milardi, Danilo; Zito, Valeria M. V.; Vecchio, Graziella

New journal of chemistry (1987) (2022)

A? and Tau Interact with Metal Ions, Lipid Membranes and Peptide-Based Amyloid Inhibitors: Are These Common Features Relevant in Alzheimer’s Disease?

Giuseppe Di Natale, Giuseppina Sabatino ,Michele Francesco Maria Sciacca ,Rita Tosto, Danilo Milardi and Giuseppe Pappalardo

Molecules (Basel, Online) (2022)

Structural and dynamical determinants of a ?-sheet-enriched intermediate involved in amyloid fibrillar assembly of human prion protein

Russo, Luigi; Salzano, Giulia; Corvino, Andrea; Bistaffa, Edoardo; Moda, Fabio; Celauro, Luigi; D’Abrosca, Gianluca; Isernia, Carla; Milardi, Danilo; Giachin, Gabriele; Malgieri, Gaetano; Legname, Giuseppe; Fattorusso, Roberto

Chemical science (Camb. 2010. Print) (2022)

Silybins inhibit human IAPP amyloid growth and toxicity through stereospecific interactions

Garcia-Vinuales S.; Ilie I.M.; Santoro A.M.; Romanucci V.; Zarrelli A.; Di Fabio G.; Caflisch A.; Milardi D.

Biochimica et biophysica acta. Proteins and proteomics (2022)

Insulin-Degrading Enzyme Is a Non Proteasomal Target of Carfilzomib and Affects the 20S Proteasome Inhibition by the Drug

Tundo G.R.; Sbardella D.; Oddone F.; Grasso G.; Marini S.; Atzori M.G.; Santoro A.M.; Milardi D.; Bellia F.; Macari G.; Graziani G.; Polticelli F.; Cascio P.; Parravano M.; Coletta M.

Biomolecules (2022)

Silybins are stereospecific regulators of the 20S proteasome

Persico M.; Garcia-Vinuales S.; Santoro A.M.; Lanza V.; Tundo G.R.; Sbardella D.; Coletta M.; Romanucci V.; Zarrelli A.; Di Fabio G.; Fattorusso C.; Milardi D.

Bioorganic & medicinal chemistry (Print) (2022)

Modulation of the 20S Proteasome Activity by Porphyrin Derivatives Is Steered through Their Charge Distribution

Persico, Marco; Santoro, Anna Maria; D’urso, Alessandro; Milardi, Danilo; Purrello, Roberto; Cunsolo, Alessandra; Gobbo, Marina; Fattorusso, Roberto; Diana, Donatella; Stefanelli, Manuela; Tundo, Grazia R.; Sbardella, Diego; Coletta, Massimo; Fattorusso, Caterina

International journal of molecular sciences (Print) (2022)

Synthesis of New Tyrosol-Based Phosphodiester Derivatives: Effect on Amyloid ? Aggregation and Metal Chelation Ability

Romanucci, Valeria; Giordano, Maddalena; De Tommaso, Gaetano; Iuliano, Mauro; Bernini, Roberta; Clemente, Mariangela; Garcia-Viñuales, Sara; Milardi, Danilo; Zarrelli, Armando; Di Fabio, Giovanni

ChemMedChem (Print) (2021)

Investigation on the solid-phase synthesis of silybin prodrugs and their timed-release

Valeria Romanucci a, Maddalena Giordano a, Rita Pagano a, Stefania Zimbone b, Maria Laura Giuffrida b, Danilo Milardi b, Armando Zarrelli a, Giovanni Di Fabio a,*

Bioorganic & medicinal chemistry (Online) (2021)

The interplay between lipid and A? amyloid homeostasis in Alzheimer’s Disease: risk factors and therapeutic opportunities

Garcia-Vinuales S.; Sciacca M.F.M.; Lanza V.; Santoro A.M.; Grasso G.; Tundo G.R.; Sbardella D.; Coletta M.; Grasso G.; La Rosa C.; Milardi D.

Chemistry and physics of lipids (Print) (2021)

Structural characterization of the thermal unfolding pathway of human VEGFR1D2 domain

Donatella Diana, Rossella Di Stasi, Sara García-Viñuales, Lucia De Rosa, Carla Isernia, Gaetano Malgieri, Danilo Milardi, Luca D. D’Andrea and Roberto Fattorusso

The FEBS journal (Online) (2021)

Probing the helical stability in a VEGF-mimetic peptide

De Rosa L.; Diana D.; Di Stasi R.; Romanelli A.; Sciacca M.F.M.; Milardi D.; Isernia C.; Fattorusso R.; D’Andrea L.D.

Bioorganic chemistry (Print) (2021)

Tau/A? chimera peptides: A Thioflavin-T and MALDI-TOF study of A? amyloidosis in the presence of Cu(II) or Zn(II) ions and total lipid brain extract (TLBE) vesicles

Sciacca M.F.M.; Di Natale G.; Milardi D.; Pappalardo G.

Chemistry and physics of lipids (Print) (2021)

Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes

Milardi, Danilo; Gazit, Ehud; Radford, Sheena E.; Xu, Yong; Gallardo, Rodrigo U.; Caflisch, Amedeo; Westermark, Gunilla T.; Westermark, Per; Rosa, Carmelo La; Ramamoorthy, Ayyalusamy

Chemical reviews (2021)