Matteo Marzi

Post Doc
POST DOC

Research Lines

Genomic Science

Center

cgs-semm

About

  • 2011 “Phd in Molecular Medicine” (4 years degree at the European School of Molecular Medicine, within the IFOM-IEO-CAMPUS)
  • 2006: “Laurea magistrale in Biotecnologie Farmaceutiche” (5 years degree; final mark 110 cum laude) at the University of Milan

Projects

 

  • Winner of a 2014 AIRC/Fondazione Cariplo individual grant TRIDEO (Transforming IDeas in Oncological research award). 
    • Uncovering microRNA dynamic degradation in cancer through metabolic labeling

A widespread repression of miRNA has been described in almost every type of cancer, caused by promoter silencing, transcriptional regulation or alterations in miRNA processing. Our hypothesis is that also altered miRNAs degradation contributes to miRNA repression in cancer. This idea was suggested by recent data showing that miRNAs can be degraded upon interaction with their targets, if the targets fulfill precise requirements in terms of complementarity. We developed a way to circumvent this problem by exploiting 4S-Uridine (4SU), a low-frequency naturally occurring modified base that can be incorporated in place of Uridine into the nascent RNA. 4SU serves as an attachment point for a thiol-specific biotinylation that allow the separation of newly transcribed RNA from the total RNA population. This method was originally developed to study the dynamics of transcription and decay of mRNAs. We adapted the protocol to microRNAs: 4SU is added to the medium for a period of time sufficient to label also mature microRNAs (3hrs), then 4SU is removed from the medium and the decay of labeled species is monitored, at different time points, during the chase period. We can isolate enough materials to generate high-throughput sequencing libraries, thus we can simultaneously analyze the decay of all expressed miRNAs and their 3’ modified forms (“isomiRs”, that can display differential stability compared to canonical miRNAs). We applied this approach to analyze the dynamics of miRNA decay under physiological conditions (growing vs. quiescent cells) and under oncogenic stimuli. 

  • Winner of a 2016 CARIPLO individual grant "Biomedical Research conducted by young researchers 2016".
    • Study of target-induced microRNA degradation and competing endogenous RNA mechanisms by CRISPR/Cas9 mediated deletion of high affinity target sites

In this project, I propose to rule out the hypothesis that endogenous RNA targets could regulate miRNAs by a target-induced miRNA decay (TIMD) mechanism. By a rigorous pipeline that combines a series of bioinformatics and experimental analyses, I will identify and validate a group of endogenous targets involved in TIMD.To explicitly validate this hypothesis, our team will exploit CRISPR/Cas9 gene editing to delete miRNA-responsive elements (MREs) from the 3'UTR of candidate transcripts, to specifically interfere with miRNA:target interaction while keeping mRNA and miRNA expression at their endogenous levels (WP1). State-of-the-art quantitation of gene and miRNA expression by digital PCR and RNA-sequencing will be used to measure miRNA and target expression upon manipulation. Additional tools specifically developed in our lab, namely IsomiRage (for the analysis of miRNA isoforms by small-RNA sequencing) and 4SU-labelling (to monitor miRNA decay), will be also exploited to achieve a comprehensive characterization of the bidirectional effects associated with target:miRNA interaction. 

IIT Publications

  • 2018
  • Bonetti P., Montserrat C., Panebianco F., Tordonato C., Santoro S., Marzi M.J.iit, Pelicci P.G., Ventura A., Nicassio F.iit

    Dual role for miR-34a in the control of early progenitor proliferation and commitment in the mammary gland and in breast cancer

    Oncogene
  • Ghini F.iit, Rubolino C.iit, Climent M.iit, Simeone I.iit, Marzi M.J.iit, Nicassio F.iit
    DOI

    Endogenous transcripts control miRNA levels and activity in mammalian cells by target-directed miRNA degradation

    Nature Communications, vol. 9, (no. 1)
  • Marzi M.J.iit, Nicassio F.iit
    DOI

    Uncovering the stability of mature miRNAs by 4-thio-uridine metabolic labeling

    Methods in molecular biology (Clifton, N.J.), vol. 1823, pp. 141-152
  • 2017
  • Ghini F., Marzi M.J.iit, Nicassio F.iit

    Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-induced miRNA degradation mechanism (TIMD)

    2nd International Conference on the Long and the Short of Non-Coding RNAs
  • Ghini F., Marzi M.J.iit, Nicassio F.iit

    Endogenous transcripts control miRNA levels and activity in mammalian cells by a target-induced miRNA degradation mechanism (TIMD)

    EMBO | EMBL Symposia :Non-coding Genome
  • Marzi M.J.iit, Tordonato C., Nicassio F.iit

    Long non-coding RNAs (lncRNAs) and stem cells properties in breast cancer

    Keystone Symposia: Noncoding RNAs: From Disease to Targeted Therapeutics (J5)
  • Marinaro F.iit, Marzi M.J.iit, Hoffmann N.iit, Amin H.iit, Pelizzoli R.iit, Niola F.iit, Nicassio F.iit, De Pietri Tonelli D.iit
    DOI

    MicroRNA-independent functions of DGCR8 are essential for neocortical development and TBR1 expression

    EMBO Reports, vol. 18, (no. 4), pp. 603-618
  • Marzi M.J.iit, Ghini F., Rubolino C., Simeone I.iit, Nicassio F.iit

    Study of Target-Induced miRNA Degradation by CRISPR/Cas9 deletion of miRNA responsive elements

    XVI CONGRESSO REGIONALE SISA-XI CONGRESSO NAZIONALE SITeCS
  • Pons-Espinal M.iit, de Luca E.iit, Marzi M.J., Beckervordersandforth R., Armirotti A.iit, Nicassio F., Fabel K., Kempermann G., De Pietri Tonelli D.iit
    DOI

    Synergic Functions of miRNAs Determine Neuronal Fate of Adult Neural Stem Cells

    Stem Cell Reports, vol. 8, (no. 4), pp. 1046-1061
  • 2016
  • Marzi M.J.iit, Ghini F.iit, Cerruti B.iit, De Pretis S.iit, Bonetti P.iit, Giacomelli C.iit, Gorski M.M., Kress T.iit, Pelizzola M.iit, Muller H.iit, Amati B.iit, Nicassio F.iit
    DOI

    Degradation dynamics of micrornas revealed by a novel pulse-chase approach

    Genome Research, vol. 26, (no. 4), pp. 554-565
  • Marzi M.J.iit, Montani F., Carletti R.M., Dezi F., Dama E., Bonizzi G., Sandri M.T., Rampinelli C., Bellomi M., Maisonneuve P., Spaggiari L., Veronesi G., Bianchi F., Di Fiore P.P., Nicassio F.iit
    DOI

    Optimization and standardization of circulating MicroRNA detection for clinical application: The miR-test case

    Clinical Chemistry, vol. 62, (no. 5), pp. 743-754
  • Ghini F., Marzi M.J.iit, Nicassio F.iit

    The plasticity of miRNA pool: a novel approach to reveal mechanisms behind miRNA turnover

    PhD Thesis
  • 2015
  • Montani F., Marzi M.J.iit, Dezi F., Dama E., Carletti R.M., Bonizzi G., Bertolotti R., Bellomi M., Rampinelli C., Maisonneuve P., Spaggiari L., Veronesi G., Nicassio F.iit, Di Fiore P.P., Bianchi F.
    DOI

    MiR-test: A blood test for lung cancer early detection

    Journal of the National Cancer Institute, vol. 107, (no. 6)
  • 2014
  • Muller H.iit, Marzi M.J.iit, Nicassio F.iit
    DOI

    IsomiRage: From functional classification to differential expression of miRNA isoforms

    Frontiers in Bioengineering and Biotechnology, vol. 2, (no. SEP)
  • 2012
  • Marzi M.J., Puggioni E.M.R., Dall'Olio V., Bucci G.iit, Bernard L., Bianchi F., Crescenzi M., Di Fiore P.P., Nicassio F.iit
    DOI

    Differentiation-associated microRNAs antagonize the Rb-E2F pathway to restrict proliferation

    Journal of Cell Biology, vol. 199, (no. 1), pp. 77-95
  • 2011
  • Bianchi F., Nicassio F., Marzi M., Belloni E., Dall'Olio V., Bernard L., Pelosi G., Maisonneuve P., Veronesi G., Di Fiore P.P.
    DOI

    A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer

    EMBO Molecular Medicine, vol. 3, (no. 8), pp. 495-503

Awards

AWARDS

  • Winner of the "Giovani Ricercatori" prize at the regional symposium of SISA lombardia (Milan, Italy, October 19-21, 2017).
  • Winner of a Trainee Travel Award for a selected short presentation at the International Conference on the Long and the Short of Non-Coding RNAs (Chania, Greece, 2015).
  • Winner of the poster session at the 2nd“microRNA in biology and Disease” symposium (MACS symposia, Bologna, December 1, 2009)

 PATENTS

  • 2012 Patent application, International Publication No WO/2012/089630 A1 PCT/EP2011/073868 A METHOD TO IDENTIFY ASYMPTOMATIC HIGH-RISK INDIVIDUALS WITH EARLY STAGE LUNG CANCER BY MEANS OF DETECTING miRNAs IN BIOLOGIC FLUIDS.