• Istituto di Biologia e Patologia Molecolari


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michela.disalvio@cnr.it
MICHELA DI SALVIO
Researcher

Istitute of Molecular Biology and Pathology - National Research Council
Department of Biology and Biotecnology - Charles Darwin
Sapienza University of Rome - Istituto Genetica III, floor room 310 - P.Le A.Moro 5 00185 Roma
My main research interest is in the field of neurodegenerative disorders. In particular, I have been focused on Amyotrophic Lateral Sclerosis (ALS) which is a progressive and fatal disease due to a specific motor neuron cell death in brain and spinal cord.

Several of the identified genetic factors in ALS are deeply associated to RNA metabolism. A consistent body of evidence suggests that FUS and TDP43, proteins which are mutated in the familial form of ALS, exert important functions in the regulation of alternative splicing, RNA maturation and trafficking. Currently, by using human cell lines and Drosophila melanogaster ALS models, I am studying the molecular mechanisms underlying the pathogenesis of this disease and I am working on the identification of new genes involved in its onset.

My research activities are currently focusing on three main projects:

- the study of a physiological and functional interaction between the mitochondrial protein p32 and ALS-linked mutant form of FUS;

- identification of mRNA downstream FUS-mediated alternative splicing regulation .

- the role of hydrogen sulfide, a signaling molecule involved in several neuronal pathways, in TDP43-dependent stress response.
1.    Mirra A, Rossi S, Scaricamazza S, Di Salvio M, Salvatori I, Valle C, Rusmini P, Poletti A, Cestra G, Carrì MT, Cozzolino M. Functional interaction between FUS and SMN underlies SMA-like splicing changes in wild-type hFUS mice. Sci Rep. 2017 May 17;7(1):2033. doi: 10.1038/s41598-017-02195-0. Erratum in: Sci Rep. 2018 Apr 30;8(1):7005.

2.    Di Salvio M, Piccinni V, Gerbino V, Mantoni F, Camerini S, Lenzi J, Rosa A, Chellini L, Loreni F, Carrì MT, Bozzoni I, Cozzolino M, Cestra G. Pur-alpha functionally interacts with FUS carrying ALS-associated mutations. Cell Death Dis. 2015 Oct 22;6:e1943. doi: 10.1038/cddis.2015.295.

3.    Odorisio T, Di Salvio M, Orecchia A, Di Zenzo G, Piccinni E, Cianfarani F, Travaglione A, Uva P, Bellei B, Conti A, Zambruno G, Castiglia D. Monozygotic twins discordant for recessive dystrophic epidermolysis bullosa phenotype highlight the role of TGF-ßsignalling in modifying disease severity. Hum Mol Genet. 2014 Aug 1;23(15):3907-22. doi: 10.1093/hmg/ddu102. Epub 2014 Mar 5.

4.    Otx2 cell-autonomously determines dorsal mesencephalon versus cerebellum fate independently of isthmic organizing activity.Di Giovannantonio LG, Di Salvio M, Omodei D, Prakash N, Wurst W, Pierani A, Acampora D, Simeone A. Development. 2014 Jan;141(2):377-88. doi: 10.1242/dev.102954. Epub 2013 Dec 11.

5.    Di Giovannantonio LG*, Di Salvio M*, Acampora D*, Prakash N, Wurst W, Simeone A.Otx2 selectively controls the neurogenesis of specific neuronal subtypes of the ventral tegmental area and compensates En1-dependent neuronal loss and MPTP vulnerability. Dev Biol. 2013 Jan 1;373(1):176-83. doi: 10.1016/j.ydbio.2012.10.022. Epub 2012 Oct 29.

6.    Di Salvio M, Di Giovannantonio LG, Acampora D, Prosperi R, Omodei D, Prakash N, Wurst W, Simeone A. Otx2 controls neuron subtype identity in ventral segmenta area and antagonizes vulnerability to MPTP. Nat Neurosci. 2010 Dec;13(12):1481-8. doi: 10.1038/nn.2661. Epub 2010 Nov 7.

7.    Fernando García-Moreno, MaríaPedraza, Luca Di Giovannantonio, Michela Di Salvio, Laura Lopez-Mascaraque, Antonio Simeone and Juan De Carlos A neuronal migratory pathway crossing from diencephalon to telencephalon populates amygdala nuclei. Nat Neurosci. 2010 Jun;13(6):680-9. doi: 10.1038/nn.2556. Epub 2010 May 23.

8.    Michela Di Salvio, Luca Giovanni Di Giovannantonio, Daniela Omodei, Dario Acampora and Antonio Simeone Otx2 expression is restricted to dopaminergic neurons of the ventral tegmental area in the adult brain. Int J Dev Biol. 2010;54(5):939-45. doi: 10.1387/ijdb.092974ms.

9.    Acampora D, Di Giovannantonio LG, Di Salvio M, Mancuso P, Simeone A. Selective inactivation of Otx2 mRNA isoforms reveals isoform-specific requirement for visceral endoderm anteriorization and head morphogenesis and highlights cell diversity in the visceral endoderm. Mech Dev. 2009 Oct;126(10):882-97. doi: 10.1016/j.mod.2009.07.003. Epub 2009 Jul 15

10.    NilimaPrakash, Eduardo Puelles, Kristine Freude, Dietrich Trümbach, Daniela Omodei, Michela Di Salvio, Lori Sussel, Johan Ericson, MaikeSander, Antonio Simeone and Wolfgang Wurst Nkx6-1 controls the identity and fate of red nucleus and oculomotor neurons in the mouse midbrain. Development. 2009 Aug;136(15):2545-55. doi: 10.1242/dev.031781.
EDUCATIONAND QUALIFICATIONS

2008: MSc degree in Medical Biotechnologies (9/S)
University of Naples “Federico II”, Dept of Molecular Medicine and Medical Biotechnology

2016: International PhD in Molecular Oncology, Experimental Immunology and Development of Innovative Therapies. University “Magna Graecia”, Catanzaro, Italy


SCIENTIFIC POSITIONS AND RESEARCH EXPERIENCE

September 2019-present: CNR research scientist appointment at IBPM-CNR

2016 – 19:  Research Fellow, IBPM-CNR
AIRC Project:  Exploiting the Drosophila model system to investigate the function of human proteins involved in telomere maintenance  
Supervisor: Prof. Maurizio Gatti

2015 –16:  Research Fellow, University of Rome "Tor Vergata”, at IBPM-CNR
Project (Frick Foundation for ALS Research): Biochemical and genetic analysis of the interaction FUS-p32 .
Supervisor: Prof. Maria Teresa Carrì

2013-14: Research Fellow, IBPM CNR
ARISLA Project: Biochemical and genetic analysis of the interaction between FUS and NonA.
Supervisor: Dott. Gianluca Cestra.

2012- 13: Research contract, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, Italy - Laboratory of Molecular and Cell Biology
Project IDI DEBRA 2011: Modifying genes in phenotypically discordant siblings with recessive dystrophic epidermolysis bullosa: role of signaling pathways regulating wound healing and inflammation.
Supervisor: Dr. Giovanna Zambruno.

2011: Research contract, Istituto Dermopatico dell'Immacolata IDI-IRCCS, Rome, Italy - Laboratory of Molecular and Cell Biology
Project RC10/1.2: Pathogenetic mechanisms and genotype-phenotype correlation in inherited diseases of epithelial adhesion
Supervisor: Dr. Daniele Castiglia

2010- 11: Research contract), Chieti University “G. D'Annunzio”, at  the National Cancer Institute Regina Elena, Rome - Molecular Oncogenesis Laboratory,
AIRC Project:   Regulation of p53 function by HIPK2
Supervisor: Dr. G. D’Orazi

2010: Research contract, Ceinge Biotecnologie avanzate S.c.a.r.l., Naples, Italy
EU Project, FP7-Health:  Molecular coding and subset specification of dopamine neurons gene rating the meso-limbic and nigro-striatal system  
Supervisor: Dr. Antonio Simeone

2009: Research contract, Ceinge Biotecnologie avanzate S.c.a.r.l., Naples, Italy
AIRC Project:  Otx2 genes in medulloblastoma: a genetic study to unravel their role in tumorigenesis of cerebellar progenitors.
Supervisor: Dott. Antonio Simeone