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.
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.
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.
Claudia Scotti, PI
Phone: (+39) 0382 986335
Claudia Scotti, PI, Researcher
Maristella Maggi, Researcher
Greta Pessino, Post-doc
Silvia Calandra, MSc Fellow
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.