Marco Venturin
Marco Venturin
affiliation: Università di Milano
research area(s): Molecular Biology, Genetics And Genomics
Course: Biomolecular Sciences
University/Istitution: Università di Milano
Assistant Professor in Applied Biology
Department of Biology and Genetics for Medical Sciences
University of Milan


February 1999: M.Sc. in Biology, University of Milan, Italy. Research field: genomics

October 2000: 1st Bioinformatics Course, European School of Genetic Medicine, European Genetics Foundation, Sestri Levante, Italy

May 2004: Ph.D. in in Neurology, Psychiatry and Neurogenetics, University of Genoa, Italy. Research field: genomics/molecular genetics and cytogenetics

April 2006: 1st level Master in Bioinformatics, University of Turin, Italy. Research field: comparative genomics

June 2006: Course "Molecular and cellular neurobiology", organized by the Ph.D. School in Biomolecular Sciences, University of Milan, Italy

November 2008: Course "Functional characterization of genetic variants", organized by SIGU (Italian Society of Human Genetics), Genoa, Italy

September 2010: Course "Next-Generation Sequencing for biomedical Omics 2010: Tools & Challenges", organized by FBK (Fondazione Bruno Kessler) and CIBIO, University of Trento, Castel Ivano (TN), Italy


2000-2004: Ph.D. Student in Neurology, Psychiatry and Neurogenetics, University of Genoa, Italy. Fields of interest: genomics, molecular genetics and cytogenetics

July-September 2003: EMBO Short Term Fellowship, EMBL Computational Biology Unit, Heidelberg, Germany. Fields of interest: bioinformatics

2004-2005: Postdoctoral Fellow, University of Milan, Italy. Fields of interest: molecular genetics and cytogenetics, gene expression, mutation analysis, bioinformatics

2005-present: Member of AIBG (Italian Association of Biology and Genetics)

2006-2008: Researcher/Assistant Professor, Dept. of Biology and Genetics for Medical Sciences, Medical Faculty, University of Milan, Italy. Fields of interest: post-transcriptional regulation of gene expression, genetic basis of diseases, analysis of gene expression, mutation analysis, bioinformatics

2009-present: Confirmed Researcher/Assistant Professor, Dept. of Biology and Genetics for Medical Sciences, Medical Faculty, University of Milan, Italy. Fields of interest: post-transcriptional regulation of gene expression, genetic basis of diseases, analysis of gene expression, mutation analysis, bioinformatics


Fondo per gli Investimenti della Ricerca di Base 2008 - Futuro in Ricerca - MIUR (Italian Ministry of Education, University and Research)
Project duration: 3 years (2011-2013)
My primary research activity is focused on the understanding of the mechanisms of post-transcriptional regulation of gene expression mediated by RNA-binding proteins and microRNAs, and on the possible involvement of these mechanisms in the pathogenesis of cognitive disorders and neurodegenerative diseases (especially Alzheimer's disease).
Further research interests concern the study of the molecular basis and pathogenic mechanisms underlying some human genetic diseases (NF1 microdeletion syndrome, Noonan syndrome, non syndromic mental retardation).
RECENT PUBLICATIONS (last five years)

Moncini S.*, Bevilacqua A.*, Venturin M., Fallini C., Ratti A., Nicolin A. and Riva P. (2007) The 3' untranslated region of human Cyclin-Dependent Kinase 5 Regulatory subunit 1 contains regulatory elements affecting transcript stability. BMC Mol Biol, 8: 111.

Orzan F.*, Stroppi M.*, Venturin M., Valero M.C., Hernández C. and Riva P. (2008) Breakpoint characterization of a novel NF1 multiexonic deletion case showing expression of the mutated allele. Neurogenetics, 9: 95-100.

Salvi A., Sabelli C., Moncini S., Venturin M., Arici B., Riva P., Portolani N., Giulini S.M., De Petro G. and Barlati S. (2009) MicroRNA-23b mediates urokinase and c-met down modulation and a decreased migration of human hepatocellular carcinoma cells. FEBS J, 276: 2966-82.

Martinoli E., Zuccotti G.V., Pogliani L., Volonte' M., Venturin M., Fortina P., Ertel A., Redaelli S., Riva P. and Dalpra' L. (2010) A tandem duplication of chromosome 21 in a newborn showing a phenotype inconsistent with Down syndrome. Am J Med Genet A, 152A: 1043-5.

Longoni M.*, Moncini S.*, Cisternino M., Morella I.M., Ferraiuolo S., Russo S., Mannarino S., Brazzelli V., Coi P., Zippel R., Venturin M. and Riva P. (2010) Noonan Syndrome associate with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutation. Am J Med Genet A, 152A:2176-84.

Moncini S., Salvi A., Zuccotti P., Viero G., Quattrone A., De Petro G., Barlati S., Venturin M. and Riva P. (2011) The role of miR-103 and miR-107 in regulation of CDK5R1 expression and in cellular migration. PLoS ONE 6: e20038.
Project Title:
Regulation of CDK5R1 expression by microRNAs and its involvement in Alzheimer's disease
Alzheimer's disease (AD) is one of the most common types of senile dementia, characterized by intracellular neurofibrillary tangles (NFTs), composed of hyperphosphorylated Tau, and extracellular senile plaques, formed by the fibrillary β-amyloid (Aβ). Different kinases have been implicated in the pathogenic processes associated with AD. In particular, the CDK5 kinase has been suggested to have a prime role in the pathogenesis of AD by hyperphophorilating Tau, by mediating the neurotoxic effects triggered by Aβ, and by contributing to Aβ production. CDK5 requires for its activity the interaction with the regulatory subunit p35 or with its proteolytic product p25. Noteworthy, overexpression of p25 in transgenic mice results in increased CDK5 activity and hyperphosphorylation of Tau. p35 is encoded by CDK5R1 (Cyclin-Dependent Kinase 5 Regulatory subunit 1), a gene with a very large 3'UTR which contains several microRNA (miRNA) predicted target sites. MiRNAs are small regulatory RNAs with roles in neurodevelopment, neuroplasticity, apoptosis, and other fundamental neurobiological processes. A number of recent papers raise the possibility that misregulation of miRNAs could have a role in AD, by altering the expression of key proteins, such as BACE1 and APP. Interestingly, some of these miRNAs (miR-107, miR-15a) have many predicted target sites within CDK5R1 3'UTR.
It is currently unknown if p25/p35 levels are regulated by miRNAs and if these mechanisms are misregulated in AD, leading to an abnormal CDK5 phosphorylation activity, with an implication in AD pathogenesis. We first evidenced an inverse correlation between p35 and miR-107/103 levels in different cell lines. A significant reduction of CDK5R1 mRNA and p35 levels was observed after transfection of SK-N-BE neuroblastoma cells with the miR-103 or miR-107 precursor (pre-miR-103 or pre-miR-107). Conversely, p35 levels significantly increased following transfection of the corresponding antagonists (anti-miR-103 or anti-miR-107). Furthermore, we demonstrated, by means of luciferase assays, that miR-103 and miR-107 are able to directly interact with the CDK5R1 3'UTR, in correspondence of a specific target site. These data indicate that miR-107 and miR-103 are able to regulate p35 expression and allow us to hypothesize that a miRNA-mediated mechanism may influence CDK5 activity and the associated molecular pathways.
The present project is aimed at: to elucidate the mechanisms by which miR-107/103 and other miRNAs can regulate the expression of p35; to measure the miRNA, CDK5R1 and p25/p35 levels, the CDK5 phosphorylation activity and the Tau phosphorylation, in AD and control brain tissues, in order to evaluate if there is an inverse correlation between the levels of miRNAs and the levels of p25/p35 and CDK5 activity on Tau; to explore the possibility of a post-transcriptional modulation of CDK5 activity by transfecting miRNAs/anti-miRNAs in suitable cellular systems. The understanding of how CDK5 activity is affected by miRNAs through p35 regulation, besides providing new insights on the molecular mechanisms of AD, might allow the identification of new pharmacological targets to be used as a starting point for the setting up of new therapeutic strategies for the cure of AD.