Stefano Duga
Stefano Duga
affiliation: Università di Milano
research area(s): Molecular Biology, Genetics And Genomics
Course: Biomolecular Sciences
University/Istitution: Università di Milano
Dr. Stefano Duga graduated in Veterinary Medicine summa cum laude in 1994. After finishing his PhD in Biotechnology at the University of Milan in 1997, he won a one-year Fellowship from the European Community. After a 3-years Post-doctoral fellowship in Human Genetics he became Assistant Professor (2001) and then Associate Professor of Molecular Biology (2006) at the Medical Faculty of Milan. He is presently working at the Department of Biology and Genetics for Medical Sciences.
During is training period he followed international courses at the University of Zurich (in 1998) and at the Cold Spring Harbor Laboratory (2004).
He was awarded with prestigious international awards: "ISTH Young Investigator Award 1999" of the International Society on Thrombosis and Haemostasis."Prize on Congenital Coagulation Disorders" of the Fondazione Angelo Bianchi Bonomi for the year 1999. Bayer Hemophilia Awards: Early Career Investigator Award for the year 2006.
He is acting as reviewer for the following international journals: Circulation, Blood, Human Mutation, FEBS Letters, Journal of Throbosis of Haemostasis, Hematologica - The Hematology Journal, British Journal of Haematology, Thrombosis and haemostasis, Haemophilia, Blood Coagulation and Fibrinolysis, Neuroreport, Epilepsia.
He has been founded in 2011 by different granting agencies: the Italian Telethon (2 projects), the FFC (Fondazione per la Ricerca sulla Fibrosi Cistica), the Fondazione Grigioni per il Morbo di Parkinson. In the past few years, his research group received grants also from FISM (Fondazione Italiana Sclerosi Multipla), MIUR, Bayer, IRCCS Policlinico of Milan.
He is author of 74 original publications in international peer-reviewed scientific journals (cited in PubMed) with a total Impact Factor (ISI 2010) of 456; h-index = 18.
The main research interests of Prof. Stefano Duga concern the regulation of gene expression at the post-transcriptional level and the study of the pathogenic mechanisms underlying different Mendelian (rare inherited coagulation disorders) and complex (juvenile myocardial infarction, Parkinson) diseases. His studies particularly focused on the modulation of splicing and mRNA stability in both physiologic and pathologic conditions.
In the last year his research group also focused on next-generation sequencing approaches to the identification of the genetic basis of human inherited diseases, in particular inherited hearing loss, cystic fibrosis, and Parkinson disease.
He is author of 74 original publications in international peer-reviewed scientific journals (cited in PubMed) with a total Impact Factor (ISI 2010) of 456; h-index = 18

Selected publications:

1. Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, Burnett MS, Devaney JM, Knouff CW, Thompson JR, Horne BD, Stewart AF, Assimes TL, Wild PS, Allayee H, Nitschke PL, Patel RS; Myocardial Infarction Genetics Consortium; Wellcome Trust Case Control Consortium, Martinelli N, Girelli D, ..... .......Elosua R, Marrugat J, Lucas G, Subirana I, Sala J, Ramos R, Salomaa V, Havulinna AS, Peltonen L, Melander O, Berglund G, Voight BF, Kathiresan S, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Musunuru K, Daly MJ, Purcell S, Schwartz SM, Yee J, Kathiresan S, Lucas G, Subirana I, Elosua R, Surti A, Guiducci C, Gianniny L, Mirel D, Parkin M, Burtt N, Gabriel SB.
Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet. 2011;377:383-92. (IF=30.758)

2. Guella I, Paraboschi EM, van Schalkwyk WA, Asselta R, Duga S. Identification of the first Alu-mediated large deletion involving the F5 gene in a compound heterozygous patient with severe factor V deficiency. Thromb Haemost. 2011;106(2). (IF=4.701)

3. Asselta R, Rimoldi V, Guella I, Soldà G, De Cristofaro R, Peyvandi F, Duga S. Molecular characterization of in-frame and out-of-frame alternative splicings in coagulation factor XI pre-mRNA. Blood. 2010;115:2065-72 (IF=10.558)

4. Assimes TL, Holm H, Kathiresan S, Reilly MP, Thorleifsson G, Voight BF, ...... Asselta R, Duga S, Musunuru K, Daly MJ, Purcell S, ....... O'Donnell CJ, Spertus JA, Siscovick D, Schwartz SM, Becker D, Thorsteinsdottir U, Stefansson K, Schunkert H, Samani NJ, Quertermous T. Lack of association between the Trp719Arg polymorphism in kinesin-like protein-6 and coronary artery disease in 19 case-control studies. J Am Coll Cardiol. 2010;56:1552-63. (IF=14.292)

5. Castaman G, Platè M, Giacomelli SH, Rodeghiero F, Duga S. Alterations of mRNA processing and stability as a pathogenic mechanism in von Willebrand factor quantitative deficiencies. J Thromb Haemost. 2010;8:2736-42 (IF=5.439)

6. Guella I, Asselta R, Tesei S, Zini M, Pezzoli G, Duga S. The PDXK rs2010795 variant is not associated with Parkinson disease in Italy. Ann Neurol. 2010;67:411-2 (IF=10.746)

7. Platè M, Duga S, Baronciani L, La Marca S, Rubini V, Mannucci PM, Federici AB, Asselta R. Premature termination codon mutations in the von Willebrand factor gene are associated with allele-specific and position-dependent mRNA decay. Haematologica. 2010;95:172-4 (IF=6.532)

8. Guella I, Asselta R, Ardissino D, Merlini PA, Peyvandi F, Kathiresan S, Mannucci PM, Tubaro M, Duga S. Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population. J Lipid Res. 2010;51:3342-9. (IF=6.115)

9. Mannucci PM, Asselta R, Duga S, Guella I, Spreafico M, Lotta L, Merlini PA, Peyvandi F, Kathiresan S, Ardissino D. The association of factor V Leiden with myocardial infarction is replicated in 1880 patients with premature disease. J Thromb Haemost. 2010;8:2116-21. (IF=5.439)

10. Guella I, Pistocchi A, Asselta R, Rimoldi V, Ghilardi A, Sironi F, Trotta L, Primignani P, Zini M, Zecchinelli A, Coviello D, Pezzoli G, Del Giacco L, Duga S, Goldwurm S. Mutational screening and zebrafish functional analysis of GIGYF2 as a Parkinson-disease gene. Neurobiol Aging. 2010. [Epub ahead of print] (IF=6.634)

11. Myocardial Infarction Genetics Consortium*, Kathiresan S, Voight BF, Purcell S, Musunuru K, Ardissino D, Mannucci PM, ...... Stage 1 data analysis., Voight BF, Kathiresan S, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Musunuru K, Daly MJ, Purcell S; ...... Kathiresan S, Ardissino D, Mannucci PM, Siscovick D, O'Donnell CJ, Samani NJ, Melander O, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Altshuler D. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009;41:334-341 (IF= 36,377)

12. Dall"Osso C, Duga S, Locatelli N, Spreafico M, Afrasiabi A, Pechlaner C, Peyvandi F, Tenchini ML, Asselta R. Molecular characterization of 3 novel splicing mutations causing factor V deficiency and analysis of the FV gene splicing pattern. Haematologica. 2008;93:1505-13. (IF=6.532)

13. Zadra G, Asselta R, Tenchini ML, Castaman G, Seligsohn U, Mannucci PM, Duga S. Simultaneous genotyping of coagulation factor XI type II and type III mutations by multiplex real-time PCR reveals their prevalence in healthy and FXI-deficient Italians. Haematologica. 2008;93:715-21. (IF=6.532)

Project Title:
Whole-exome sequencing applied to the study of the genetic basis of Parkinson disease
Overall Objectives
This project aims to discover new genes involved in recessive Mendelian form of Parkinson Disease (PD) exploiting the recent development of exon capture and next-generation sequencing technologies.
Specific aims
The specific aims are: 1) to capture and sequence the exome of PD probands of recessive families (only siblings affected with consanguineous parents) and to select the variants potentially causative; 2) to verify if selected variants are specific for PD analysing a large panel of cases and controls; 3) to search the candidate genes in a group of potentially recessive PD cases; 4) phenotype characterization of mutation carriers
In recent years, the identification of genetic causes of PD has greatly contributed to understanding the pathogenesis of this disease. Unfortunately, it is estimated that only a minority of the underlying genetic causes of familial PD have been explained to date. The recent development of exon capture and next-generation sequencing technologies now allows screening of cohorts for rare variants at a genome-wide scale in an economically feasible way.
Description of the project
To accomplish this goal, we will focus on 10 PD patients derived from 7 families with consanguineous parents and 2 or more affected siblings. Such cases are highly suggestive of a recessive form of PD and represent a valuable resource for the identification of PD causative genes as their inbred nature overcomes several of the limitations that exist in the use of exome sequencing. We will describe how we plan to isolate candidate PD-associated variants through a bioinformatic analysis and how we intend to validate our findings in a large PD cohort
Anticipated output
We are confident that the proposed project will lead to the discovery of one or more novel causative genes for recessive PD. Such a result will shed new light on PD pathogenesis and show new therapeutic target probably valid also in the more common complex PD.