Sergio Comincini
Sergio Comincini
affiliation: Università di Pavia
research area(s): Cancer Biology, Neuroscience
Course: Genetics, Molecular and Cellular Biology
University/Istitution: Università di Pavia
Graduated in Biological Sciences (1991) at the University of Pavia. PhD in Biotechnology applied to Veterinary Sciences, at the University of Milan. He was granted UE contract (UE CE FAIR5 -CT97 3311) in the IV Biotechnology Framework of the “Analysis of molecular factors affecting BSE and scrapie susceptibility” from 1998 to 2001. PostDoc contract at the University of Pavia from 2001 to 2002. Full time researcher and Professor of Methods in neurosciences at the University of Pavia from 2002. Director of the Functional Oncogenomics laboratory at the Department of Genetics and Microbiology (University of Pavia).
He has been working on the molecular genetics of the domestic animals, of the animal parasites and of the clinically relevant microrganisms, since 1993. From 1996 he is studying transmissible spongiform encephalophaties of animals (BSE and scrapie) and he personally coordinated a research group within the UE contract (UE CE FAIR5-CT97 3311) in the IV Biotechnology Framework of the “Analysis of molecular factors affecting BSE and scrapie susceptibility”, at the IDVGA-CNR Institute of Milan. In this project he first described the entire bovine prion locus genomic sequence as well as the discovery and the expression profiles studies of two novel genes, rasfadin and doppel. Lately he has contributed to the description of the molecular mechanisms of doppel gene regulation in the bovine.
From 1998 he has been active on the research of novel tumor molecular markers, establishing important national and international collaborations. Within this research he firstly described the involvement of the doppel gene in the astrocytic (granted as national project funded by MIUR 2003) and in the leukaemic tumor progression.
Within the 2005 and 2008 PRIN Research Project he has been the national coordinator for a functional study of the doppel gene in the glial tumor a for a projecte aimed to induce autophagy cell death in glial tumor cells.

The main scientific competences are related to molecular and bioinformatics-based gene expression and gene-interference and protein-protein interaction studies, to the establishment of tumor astrocytic cell culture models, to the induction of cell death (in particular autophagy).

He is author of 38 publications on peer-reviewed journal and of 40 communications to congresses, 3 book-chapters and one international patent. He has participated to numerous International Congresses as invited speaker.
The Laboratory has been working on the molecular biology and cellular studies within human astrocytic tumors, focusing on DIAGNOSTIC and THERAPEUTIC targets. For diagnosis, the mission of the Laboratory is to identify and to functional characterize gene and protein sequences potentially involved in the astrocytic tumor progression: these studies will clearly be helpful to establish molecular-based tumor classification criteria and to improve current diagnostic paradigms based on histopathological diagnosis. Particular emphasis has been recently devoted to the doppel (PRND) gene and to the corresponding protein (Dpl), recently characterize as paralogue of the prion gene. Interestingly, the gene and the protein are not expressed in the healthy CNS tissues, while ectopic expression was observed in astrocytic tumors; our studies have recently defined a clear correlation between the expression of the gene/protein and the tumor grade of malignancy (Comincini et al. 2004-2006-2007).
These studies require the tight interaction with important national Neurological and Neurosurgical clinics of Parma, Verona and Siena. In relation to the therapeutics, the Laboratory is working on the development and to the molecular/cellular characterization of a novel in vitro therapeutic approach based on the silencing and to the functional interfering of specific genes expressed in the tumor cells. The encouraging results, published in Autophagy Journal (Barbieri et al., 2011) have recently suggested additional preclinical studies using animal models and to define the biological tolerability of the investigated treatment: to this purpose, important collaboration with biotechnological and pharmaceutical Companies will be established.
Barbieri G, Palumbo S, Gabrusiewicz K, Azzalin A, Marchesi N, Spedito A, Biggiogera M, Sbalchiero E, Mazzini G, Miracco C, Pirtoli L, Kaminska B, Comincini S. Silencing of cellular prion protein (PrPC) expression by DNA-antisense oligonucleotides induces autophagy-dependent cell death in glioma cells. Autophagy. 2011 Aug 1;7(8); 840-853..

Rognoni P, Chiarelli LR, Comincini S, Azzalin A, Miracco C, Valentini G. Biochemical signatures of doppel protein in human astrocytomas to support prediction in tumor malignancy. J Biomed Biotechnol. 2010;2010:301067. Epub 2010 Oct 14.

Barbarini N, Simonelli L, Azzalin A, Comincini S, Bellazzi R. Development of a novel bioinformatics tool for in silico validation of protein interactions. J Biomed Biotechnol. 2010;2010:670125. Epub 2010 Jun 7.

Comincini S, Paolillo M, Barbieri G, Palumbo S, Sbalchiero E, Azzalin A, Russo MA, Schinelli S. Gene expression analysis of an EGFR indirectly related pathway identified PTEN and MMP9 as reliable diagnostic markers for human glial tumor specimens. J Biomed Biotechnol. 2009;2009:924565. Epub 2009 Jul 30.
Azzalin A, Sbalchiero E, Barbieri G, Palumbo, Muzzini C, Comincini S. The doppel (Dpl) protein influences in vitro migration capability in astrocytoma-derived cells. Cell Oncol. 2008;30(6):491-501.
Sbalchiero E, Azzalin A, Palumbo S, Barbieri G, Arias A, Simonelli L, Ferretti L, Comincini S. Altered cellular distribution and sub-cellular sorting of doppel (Dpl) protein in human astrocytoma cell lines. Cell Oncol. 2008;30(4):337-47.
Comincini S, Ferrara V, Arias A, Malovini A, Azzalin A, Ferretti L, Benericetti E, Cardarelli M, Gerosa M, Passarin MG, Turazzi S, Bellazzi R. Diagnostic value of PRND gene expression profiles in astrocytomas: relationship to tumor grades of malignancy. Oncol Rep. 2007 May;17(5):989-96.
Azzalin A, Del Vecchio I, Ferretti L, Comincini S. The prion-like protein Doppel (Dpl) interacts with the human receptor for activated C-kinase 1 (RACK1) protein. Anticancer Res. 2006 Nov-Dec;26(6B):4539-47.
Comincini S, Chiarelli LR, Zelini P, Del Vecchio I, Azzalin A, Arias A, Ferrara V, Rognoni P, Dipoto A, Nano R, Valentini G, Ferretti L. Nuclear mRNA retention and aberrant doppel protein expression in human astrocytic tumor cells. Oncol Rep. 2006 Dec;16(6):1325-32.
Azzalin A, Ferrara V, Arias A, Cerri S, Avella D, Pisu MB, Nano R, Bernocchi G, Ferretti L, Comincini S. Interaction between the cellular prion (PrPC) and the 2P domain K+ channel TREK-1 protein. Biochem Biophys Res Commun. 2006 Jul 21;346(1):108-15. Epub 2006 May 24.
Bellagamba F, Comincini S, Ferretti L, Valfrè F, Moretti VM.Application of quantitative real-time PCR in the detection of prion-protein gene species-specific DNA sequences in animal meals and feedstuffs. J Food Prot. 2006 Apr;69(4):891-6.
Uboldi C, Del Vecchio I, Foti MG, Azzalin A, Paulis M, Raimondi E, Vaccari G, Agrimi U, Di Guardo G, Comincini S, Ferretti L.Prion-like Doppel gene (PRND) in the goat: genomic structure, cDNA, and polymorphisms. Mamm Genome. 2005 Dec;16(12):963-71. Epub 2005 Dec 8.
Azzalin A, Del Vecchio I, Chiarelli LR, Valentini G, Comincini S, Ferretti L. Absence of interaction between doppel and GFAP, Grb2, PrPc proteins in human tumor astrocytic cells. Anticancer Res. 2005 Nov-Dec;25(6B):4369-74.
Del Vecchio I, Azzalin A, Guidi E, Amati G, Caramori T, Uboldi C, Comincini S, Ferretti L.Functional mapping of the bovine Doppel gene promoter region. Gene. 2005 Aug 15;356:101-8.
Travaglino E, Comincini S, Benatti C, Azzalin A, Nano R, Rosti V, Ferretti L, Invernizzi R. Overexpression of the Doppel protein in acute myeloid leukaemias and myelodysplastic syndromes. Br J Haematol. 2005 Mar;128(6):877-84.
Comincini S, Facoetti A, Del Vecchio I, Peoc'h K, Laplanche JL, Magrassi L, Ceroni M, Ferretti L, Nano R.Differential expression of the prion-like protein doppel gene (PRND) in astrocytomas: a new molecular marker potentially involved in tumor progression. Anticancer Res. 2004 May-Jun;24(3a):1507-17.
Hills D, Schlaepfer J, Comincini S, MacLean I, Dolf G, Ferretti L, Olsaker I, Williams JL.Sequence variation in the bovine and ovine PRNP genes. Anim Genet. 2003 Jun;34(3):183-90.
Invernizzi R, Comincini S, Travaglino E, Facoetti A, Ramajoli I, Nano R.Defective expression of the dihydrofolate reductase gene in patients with the 5q- syndrome. Haematologica. 2003 Apr;88(4):471-4.
Project Title:
Identification of microRNA sequences involved in the regulation of autophagy in human glial tumor cells