Federica Cossu

Research staff

PhD in Cellular and Molecular Biology (2012, University of Milan). Researcher at the CNR since 2017. Focus on the biological processes at the base of (i) cancer onset, progression and metastasis (breast cancer models) chemoresistance (ii) neurological disorders after pathogenic mutations of target proteins (mitochondriopaties). Integrative approaches of structural and computational biology (X-ray crystallography, Small-Angle X ray scattering, Cryo-Electron Microscopy), biochemistry and biophysics to study proteins, protein-ligands and protein-protein complexes. Structure-based identification, design, optimization of small molecules as candidates for drug development, particularly in the field of cancer therapy.

orcid://0000-0001-9753-3572,

Contact:

- Email federica.cossu@ibf.cnr.it
- Phone +39-02-23699541
- Location Milano

Website:

https://users.unimi.it/biolstru/molbd3-lab.html

Research interests:

- Structural and biochemical bases of the pathogenicity of the Apoptosis Inducing Factor (AIF) (Principal investigator)
- Type I BIR inhibitors for the regulation of NF-kB pathway (Principal investigator)
- Structure-based drug discovery
- Structural analysis of proteins involved in various human diseases and research of new therapeutic strategies

Further collaborations:

- Dr Daniele Lecis (Fondazione IRCCS Istituto Nazionale per la cura dei Tumori - Milan)
- Prof Pierfausto Seneci (Dip. di Chimica Università degli studi di Milano)
- Prof Alessandro Aliverti (Dip. di Bioscienze - Università degli studi di Milano)
- Prof Enrico Millo (CEBR - CENTRO ECCELLENZA RICERCHE BIOMEDICHE - Università degli studi di Genova)

Financial support:

- AIRC – Associazione Italiana Ricerca sul Cancro – MFAG 17083 (2015, PI: Dr. Eloise Mastrangelo) "Analisi strutturale e Ricerca di inibitori di proteine ricombinanti umane coinvolte nella regolazione del pathway NF-kB".
- Progetto DOTE-RICERCATORE da Regione Lombardia (FSE 2008) "Characterization of Pro-apoptotic compounds versus XIAP (X-linked Inhibitor of Apoptosis Protein) and study of molecular recognition through protein crystallography and virtual docking".

Key publications:

Cossu F, Sorrentino L, Fagnani E, Zaffaroni M, Milani M, Giorgino T, Mastrangelo E. Computational and Experimental Characterization of NF023, A Candidate Anticancer Compound Inhibiting cIAP2/TRAF2 Assembly. J Chem Inf Model. 2020 Oct 26;60(10):5036-5044. doi: 10.1021/acs.jcim.0c00518. Epub 2020 Sep 4. PMID: 32820924

Sorrentino L, Cossu F, Milani M, Malkoc B, Huang WC, Tsay SC, Ru Hwu J, Mastrangelo E. Structure-Activity Relationship of NF023 Derivatives Binding to XIAP-BIR1. ChemistryOpen. 2019 Apr 12;8(4):476-482. doi: 10.1002/open.201900059. eCollection 2019 Apr. PMID: 31011505

Cossu F, Milani M, Mastrangelo E, Lecis D. Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment. Comput Struct Biotechnol J. 2019 Jan 25;17:142-150. doi: 10.1016/j.csbj.2019.01.009. eCollection 2019. PMID: 30766663

Corti A, Milani M, Lecis D, Seneci P, de Rosa M, Mastrangelo E, Cossu F. Structure-based design and molecular profiling of Smac-mimetics selective for cellular IAPs. FEBS J. 2018 Sep;285(17):3286-3298. doi: 10.1111/febs.14616. Epub 2018 Aug 16. PMID: 30055105

Sorrentino L, Cossu F, Milani M, Aliverti A, Mastrangelo E. Structural bases of the altered catalytic properties of a pathogenic variant of apoptosis inducing factor. Biochem Biophys Res Commun. 2017 Aug 26;490(3):1011-1017. doi: 10.1016/j.bbrc.2017.06.156. Epub 2017 Jun 27. PMID: 28666871

Publications (9):

CHCHD4 binding affects the active site of apoptosis inducing factor (AIF): Structural determinants for allosteric regulation
Fagnani, E.; Cocomazzi, P.; Pellegrino, S.; Tedeschi, G.; Scalvini, F. G.; Cossu, F.; Da Vela, S.; Aliverti, A.; Mastrangelo, E.; Milani, M.
STRUCTURE, 2024
DOI: 10.1016/j.str.2024.02.008

Ligand Binding in Allosteric Flavoproteins: Part 1. Quantitative Analysis of the Interaction with NAD+ of the Apoptosis Inducing Factor (AIF) Harboring FAD in the Reduced State
Cocomazzi P.; Sorrentino L.; Cossu F.; Aliverti A.
methods in molecular biology (clifton n.j., online)issn: 1940-6029humana press, 2280, 2021
DOI: 10.1007/978-1-0716-1286-6_11

Structure-based identification of a new IAP-targeting compound that induces cancer cell death inducing NF-kappa B pathway
Cossu, Federica; Camelliti, Simone; Lecis, Daniele; Sorrentino, Luca; Majorini, Maria Teresa; Milani, Mario; Mastrangelo, Eloise
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL, 19, 2021
DOI: 10.1016/j.csbj.2021.11.034

Computational and Experimental Characterization of NF023, A Candidate Anticancer Compound Inhibiting cIAP2/TRAF2 Assembly
Federica Cossu, Luca Sorrentino, Elisa Fagnani, Mattia Zaffaroni, Mario Milani, Toni Giorgino, Eloise Mastrangelo
Journal of chemical information and modeling, 60, 2020
DOI: 10.1021/acs.jcim.0c00518

Structure-Activity Relationship of NF023 Derivatives Binding to XIAP-BIR1
Sorrentino L, Cossu F, Milani M, Malkoc B, Huang WC, Tsay SC, Ru Hwu J, Mastrangelo E
ChemistryOpen, 8, 2019
DOI: 10.1002/open.201900059

Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment
Cossu F, Milani M, Mastrangelo E, Lecis D
Computational and Structural Biotechnology Journal, 17, 2019
DOI: 10.1016/j.csbj.2019.01.009

Structure-based design and molecular profiling of Smac-mimetics selective for cellular IAPs
Corti A, Milani M, Lecis D, Seneci P, de Rosa M, Mastrangelo E, Cossu F
The FEBS journal, 285, 2018
DOI: 10.1111/febs.14616

Structural bases of the altered catalytic properties of a pathogenic variant of apoptosis inducing factor
Sorrentino L, Cossu F, Milani M, Aliverti A, Mastrangelo E
Biochemical and biophysical research communications, 490, 2017
DOI: 10.1016/j.bbrc.2017.06.156

Novel neurofibromatosis type 2 mutation presenting with status epilepticus
Difrancesco, Jc; Sestini, R; Cossu, F; Bolognesi, M; Sala, E; Mariani, S; Saracchi, E; Papi, Laura; Ferrarese, C
EPILEPTIC DISORDERS, 16, 2014
DOI: 10.1684/epd.2014.0647