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Neurobiology of MIRNA

Neurobiology of MIRNA

Our research focuses on noncoding RNAs in neurogenesis.

Neurogenesis is the process of new neuron (and glia) generation from Neural Progenitor Cells (NPCs). NPCs self-renew and generate committed offspring in a regulated fashion. The balance between quiescence, proliferation, differentiation and fate decision guarantees brain formation, lifelong neurogenesis and prevents tumour formation. Understanding the molecular control of NPCs fate has implications for comprehending brain malformations and age-related disorders. Over the last three decades, signaling pathways and transcriptional cascades regulating NSCs fate have been elucidated. However, the field has been mostly dominated by a gene-centric view, hence the understanding of NSCs fate remains partial.

MicroRNAs and other noncoding RNAs control NSCs fate by regulating gene expression at the transcriptional and post-transcriptional levels. Current understanding of noncoding RNA functions in NSCs fate is just at the beginning.

Activities

Activities

Our research activities are divided into two branches:

  • Brain science: The overarching goal of our research is to understand the role played by microRNAs and other noncoding RNAs in the control of NSCs fate, in mammals.
  • Health: Our aim is to use noncoding RNAs as RNA-based drugs for therapy of Brain cancer and other neural diseases.

Laboratories

Laboratories

Mol.biol. lab; cell cultures facilities (primary neural cells, immortalized lines); induced pluripotent human stem cells lab; histology lab. Access to IIT core facilities: Virus, Nikon center, Animal facility (SPF, individually ventilated cages; Surgery: electroporation, virus injection; behaviour rooms; black cages in collaboration with Tecniplast (Italy)). Deep RNA/DNA seq. and RNAi screening facility.

Collaborations

Collaborations

IIT

  • CGS@SEMM, Milan (F. Nicassio)
  • Non-coding RNAs and RNA-based therapeutics (S. Gustincich)
  • Polymers and Biomaterials (N.Tirelli) 
  • Nanotechnology for Precision Medicine (P. Decuzzi) 

National and International

  • Gerd Kempermann, Director, CRTD and Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dresden, Germany.
  • Carlos P Fitzsimons Swammerdam Institute for Life Sciences, Univ. of Amsterdam, The Netherlands.
  • Piero Carninci RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Industrial collaborations

  • Tecniplast Spa, Buguggiate, VA, Italy.

Projects

Projects
  • EU-REA, Marie Curie Actions (MCA) Call: FP7-PEOPLE-2010-RG. TITLE: NEUROGENESIS IN 22Q11.2 DELETION SYNDROME: ROLE OF microRNAs. ACRONYM: MIRNAS/22Q11DS; Project duration 2011-2015.
  • FP7-PEOPLE-2013-IEF. Acronym: “ASTROCLOCK”; Title “Astrocyte regulation of circadian behaviour”. Project Duration: 2014 – 2016.
  • AIRC - Associazione Italiana per la Ricerca sul Cancro. Title: Stimuli-Responsive Nanoparticles for eradicating different subsets of cancer cells within tumors. Collaborator; Project Duration 02/01/2014-01/01/2017.
  • Fondazione CARIPLO, Call 2015 “Biomedical research on ageing-related diseases”. Title “Role of the astrocyte-mediated circadian clock in neurodegeneration and brain aging”. Co-Prinipal investigator; Project duration 2016-2020
  • AIRC - Investigator Grant. Title: Differentiation therapy for GBM through synergic action of 11 miRNAs/drugs delivered via lipid/polymeric nanoparticles; Project Duration 2018-2022

Patents

Patents
  • Process and device for the determination of alterations in neuronal connectivity and/or morphology; 2015-02-19 | patent PAT: US 20150051109 A1
  • Composizione farmaceutica di miRNA e suoi usi terapeutici. Depositato all’ufficio brevetti Italiano Sept.,19th 2016. Rif IIT PT160330; n. 102016000093825

IIT People

IIT Publications List

Publications
2020
Gasperini C., Pelizzoli R., Lo Van A., Mangoni D., Cossu R.M., Pascarella G., Bianchini P., Bielefeld P., Scarpato M., Pons-Espinal M., Sanges R., Diaspro A., Fitzsimons C.P., Carninci P., Gustincich S., De Pietri Tonelli D.
The piRNA pathway sustains adult neurogenesis by repressing protein synthesis
bioRxiv
2019
Pons-Espinal M., Gasperini C., Marzi M.J., Braccia C., Armirotti A., Potzsch A., Walker T.L., Fabel K., Nicassio F., Kempermann G., De Pietri Tonelli D.
MiR-135a-5p Is Critical for Exercise-Induced Adult Neurogenesis
Stem Cell Reports, vol. 12, (no. 6), pp. 1298-1312
2017
Marinaro F., Marzi M.J., Hoffmann N., Amin H., Pelizzoli R., Niola F., Nicassio F., De Pietri Tonelli D.
MicroRNA-independent functions of DGCR8 are essential for neocortical development and TBR1 expression
EMBO Reports, vol. 18, (no. 4), pp. 603-618
2017
Pons-Espinal M., de Luca E., Marzi M.J., Beckervordersandforth R., Armirotti A., Nicassio F., Fabel K., Kempermann G., De Pietri Tonelli D.
Synergic Functions of miRNAs Determine Neuronal Fate of Adult Neural Stem Cells
Stem Cell Reports, vol. 8, (no. 4), pp. 1046-1061
2012
Clovis Y.M., Enard W., Marinaro F., Huttner W.B., de Pietri Tonelli D.
Convergent repression of Foxp2 3 ́UTR by miR-9 and miR-132 in embryonic mouse neocortex: Implications for radial migration of neurons
Development (Cambridge), vol. 139, (no. 18), pp. 3332-3342