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Protein engineering: from macromolecules to therapy
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Our research aims to elucidate the pathological and physiological characteristics of selected proteins by exploiting protein engineering, structural bioinformatics and X-ray techniques. Based on this information, we design new molecular tools for the diagnosis and therapy of human diseases. We are currently working on five main projects:

 

Antibody affinity maturation

In this project, in collaboration with the Growth Factors Group of our Department, we are working to define the structural basis of affinity maturation in the mouse anti-phenyloxazolone system, originally studied by Nobel laureate Cesar Milstein. The figure above shows the crystals of a Fab fragment of antibodies.

 

L-asparaginase

We are dissecting this enzyme, used as a drug in pediatric acute lymphoblastic leukemia, in order to elucidate both its mechanism of action and the basis of its problematic characteristics, and to generate improved versions of the molecule. The figure below shows a model of the E. coli enzyme with some critical residues highlighted in red.

 

Lipoprotein (a)

This protein is a novel cardiovascular risk factor, with a unique inverse relationship between its variable molecular weight, genetically determined by the number of kringle IV type 2 repeats, and its serum concentration. We are now trying to understand the biophysical characteristics and pathological potential of these different isotypes.

 

Autoantibodies in Cancer

This line of research aims to study autoantibodies as single specificities produced during the immune response to cancer, to define their structural characteristics at the atomic level and to define their epitope.

Contacts

Claudia Scotti, PI

Email: claudia.scotti@unipv.it

Phone: (+39) 0382 986335

Components

Claudia Scotti, PI, Researcher

Maristella Maggi, Researcher

Maryam Shakarami, Fellow

Silvia Calandra, PhD student

Andrea Previtali, PhD student

 

Bibliografia

Pessino G, Lonati L, Scotti C, Calandra S, Cazzalini O, Iaria O, Previtali A, Baiocco G, Perucca P, Tricarico A, Vetro M, Stivala LA, Ganini C, Cancelliere M, Zucchetti M, Guardamagna I, Maggi M. Differential effect of asparagine and glutamine removal on three adenocarcinoma cell lines. Heliyon. 2024 Aug 3;10(15):e35789. doi: 10.1016/j.heliyon.2024.e35789. PMID: 39170541; PMCID: PMC11337022.

Pessino G, Scotti C, Maggi M, Immuno-Hub Consortium. Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets. Cancers (Basel). 2024 Feb 23;16(5):901. doi: 10.3390/cancers16050901. PMID: 38473265; PMCID: PMC10931414.

Lee KY, Maggi M, Scotti C. Editorial: Biomarkers and therapeutic strategies in acute lymphoblastic leukemia. Front Cell Dev Biol. 2023 May 17;11:1211569. doi: 10.3389/fcell.2023.1211569. PMID: 37266454; PMCID: PMC10230364.

Guardamagna I, Iaria O, Lonati L, Mentana A, Previtali A, Uggè V, Ivaldi GB, Liotta M, Tabarelli de Fatis P, Scotti C, Pessino G, Maggi M, Baiocco G. Asparagine and Glutamine Deprivation Alters Ionizing Radiation Response, Migration and Adhesion of a p53null Colorectal Cancer Cell Line. Int J Mol Sci. 2023 Feb 3;24(3):2983. doi: 10.3390/ijms24032983. PMID: 36769302; PMCID: PMC9917910.

Maggi M, Scotti C. Structural Aspects of E. coli Type II Asparaginase in Complex with Its Secondary Product L-Glutamate. Int J Mol Sci. 2022 May 25;23(11):5942. doi: 10.3390/ijms23115942. PMID: 35682622; PMCID: PMC9180372.

Maggi M, Pessino G, Guardamagna I, Lonati L, Pulimeno C, Scotti C. A Targeted Catalytic Nanobody (T-CAN) with Asparaginolytic Activity. Cancers (Basel). 2021 Nov 11;13(22):5637. doi: 10.3390/cancers13225637. PMID: 34830793; PMCID: PMC8616244.

Santonastaso A, Maggi M, De Jonge H, Scotti C. High resolution structure of human apolipoprotein (a) kringle IV type 2: beyond the lysine binding site. J Lipid Res. 2020 Dec;61(12):1687-1696. doi: 10.1194/jlr.RA120001023. Epub 2020 Sep 9. PMID: 32907988; PMCID: PMC7707183.

Maggi M, Mittelman SD, Parmentier JH, Colombo G, Meli M, Whitmire JM, Merrell DS, Whitelegge J, Scotti C. A protease-resistant Escherichia coli asparaginase with outstanding stability and enhanced anti-leukaemic activity in vitro. Sci Rep. 2017 Nov 3;7(1):14479. doi: 10.1038/s41598-017-15075-4. PMID: 29101342; PMCID: PMC5670125.

Scotti C and Gherardi E. Structural basis of affinity maturation of the TEPC15/Vkappa45.1 anti-2-phenyl-5-oxazolone antibodies. J Mol Biol 359: 1161-9 (2006)