Denominazione Unità Operativa

Genetica Molecolare

Responsabile scientifico/Coordinatore

Prof. Roberto Ravazzolo

Descrizione

Ricerche di Genetica Medica su malattie genetiche rare, in particolare geni mutati, meccanismi di malattia, possibili approcci terapeutici . Per lo studio dei geni mutati,  nuovi metodi basati sul “Next Generation Sequencing” sono stati implementati sia mediante “multiple gene panels” che mediante sequenziamento completo dell’esoma.

Vengono effettuati screening di composti chimici per sviluppare nuove strategie terapeutiche per la Fibrosi Cistica, la Fibrodisplasia ossificante progressiva e il Neuroblastoma.

Elenco pubblicazioni rilevanti

  1. Fiorio P, Rosaia De Santis L, Cuoco C, Gimelli G, Gastaldi R, Bonatti F, Ravazzolo R, Bocciardi R. Hypogonadotropic hypogonadism in a trisomy X carrier: phenotype description and genotype correlation. Gynecol Endocrinol. 2015 Nov 16:1-4. [Epub ahead of print] PubMed PMID: 26572316.
  2. Prigione I, Covone AE, Giacopelli F, Bocca P, Risso M, Tripodi G, Pistorio A, Sozzi G, Airoldi I, Ravazzolo R, Pistoia V. IL12RB2 Polymorphisms correlate with risk of lung adenocarcinoma. Immunobiology. 2016 Feb;221(2):291-9. doi: 10.1016/j.imbio.2015.10.006. Epub 2015 Oct 29. PubMed PMID: 26547104.
  3. Rusmini M, Federici S, Caroli F, Grossi A, Baldi M, Obici L, Insalaco A, Tommasini A, Caorsi R, Gallo E, Olivieri AN, Marzano A, Coviello D, Ravazzolo R, Martini A, Gattorno M, Ceccherini I. Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases. Ann Rheum Dis. 2015 Sep 17. pii: annrheumdis-2015-207701. doi: 10.1136/annrheumdis-2015-207701. [Epub ahead of print] PubMed PMID: 26386126.
  4. Panza E, Escamilla-Honrubia JM, Marco-Marín C, Gougeard N, De Michele G, Morra VB, Liguori R, Salviati L, Donati MA, Cusano R, Pippucci T, Ravazzolo R, Nemeth AH, Smithson S, Davies S, Hurst JA, Bordo D, Rubio V, Seri M. ALDH18A1 gene mutations cause dominant spastic paraplegia SPG9: loss of function effect and plausibility of a dominant negative mechanism. Brain. 2016 Jan;139(Pt 1):e3. doi: 10.1093/brain/awv247. Epub 2015 Aug 21. PubMed PMID: 26297558.
  5. Bertamino M, Severino M, Schiaffino MC, Garrè ML, Bocciardi R, Ravazzolo R, Rossi A, Di Rocco M. New insights into central nervous system involvement in FOP: Case report and review of the literature. Am J Med Genet A. 2015 Nov;167A(11):2817-21. doi: 10.1002/ajmg.a.37271. Epub 2015 Aug 4. PubMed PMID: 26239063.
  6. Tomati V, Sondo E, Armirotti A, Caci E, Pesce E, Marini M, Gianotti A, Jeon YJ, Cilli M, Pistorio A, Mastracci L, Ravazzolo R, Scholte B, Ronai Z, Galietta LJ, Pedemonte N. Genetic Inhibition Of The Ubiquitin Ligase Rnf5 Attenuates Phenotypes Associated To F508del Cystic Fibrosis Mutation. Sci Rep. 2015 Jul 17;5:12138. doi: 10.1038/srep12138. PubMed PMID: 26183966; PubMed Central PMCID: PMC4505316.
  7. Bachetti T, Di Zanni E, Ravazzolo R, Ceccherini I. miR-204 mediates post-transcriptional down-regulation of PHOX2B gene expression in neuroblastoma cells. Biochim Biophys Acta. 2015 Aug;1849(8):1057-65. doi: 10.1016/j.bbagrm.2015.06.008. Epub 2015 Jul 3. PubMed PMID: 26145533.
  8. Caci E, Scudieri P, Di Carlo E, Morelli P, Bruno S, De Fino I, Bragonzi A, Gianotti A, Sondo E, Ferrera L, Palleschi A, Santambrogio L, Ravazzolo R, Galietta LJ. Upregulation of TMEM16A Protein in Bronchial Epithelial Cells by Bacterial Pyocyanin. PLoS One. 2015 Jun 29;10(6):e0131775. doi: 10.1371/journal.pone.0131775. eCollection 2015. PubMed PMID: 26121472; PubMed Central PMCID: PMC4486680.
  9. Scudieri P, Caci E, Venturini A, Sondo E, Pianigiani G, Marchetti C, Ravazzolo R, Pagani F, Galietta LJ. Ion channel and lipid scramblase activity associated with expression of TMEM16F/ANO6 isoforms. J Physiol. 2015 Sep 1;593(17):3829-48. doi: 10.1113/JP270691. Epub 2015 Jul 27. PubMed PMID: 26108457; PubMed Central PMCID: PMC4575572.
  10. Di Zanni E, Fornasari D, Ravazzolo R, Ceccherini I, Bachetti T. Identification of novel pathways and molecules able to down-regulate PHOX2B gene expression by in vitro drug screening approaches in neuroblastoma cells. Exp Cell Res. 2015 Aug 1;336(1):43-57. doi: 10.1016/j.yexcr.2015.03.025. Epub 2015 Apr 13. PubMed PMID: 25882494.
  11. Capurro V, Gianotti A, Caci E, Ravazzolo R, Galietta LJ, Zegarra-Moran O. Functional analysis of acid-activated Cl channels: properties and mechanisms of regulation. Biochim Biophys Acta. 2015 Jan;1848(1 Pt A):105-14. PubMed PMID: 25306966.
  12. Maltecca F, Baseggio E, Consolato F, Mazza D, Podini P, Young SM Jr, Drago I, Bahr BA, Puliti A, Codazzi F, Quattrini A, Casari G. Purkinje neuron Ca2+ influx reduction rescues ataxia in SCA28 model. J Clin Invest. 2015 Jan;125(1):263-74. doi: 10.1172/JCI74770. Epub 2014 Dec 8. PubMed PMID: 25485680; PubMed Central PMCID: PMC4382234.
  13. Buzio R, Repetto L, Giacopelli F, Ravazzolo R, Valbusa U. Symmetric curvature descriptors for label-free analysis of DNA. Sci Rep. 2014 Sep 24;4:6459. doi: 10.1038/srep06459. PubMed PMID: 25248631.
  14. Covone AE, Solari N, Malattia C, Pop V, Martini A, Ravelli A, Ravazzolo R. Periostin gene variants are associated with disease course and severity in juvenile idiopathic arthritis. Clin Exp Rheumatol. 2014 Sep-Oct;32(5):747-53. Epub 2014 Sep 19. PubMed PMID: 25236364.
  15. Vaccari CM, Romanini MV, Musante I, Tassano E, Gimelli S, Divizia MT, Torre M, Morovic CG, Lerone M, Ravazzolo R, Puliti A. De novo deletion of chromosome 11q12.3 in monozygotic twins affected by Poland Syndrome. BMC Med Genet. 2014 May 30;15:63. doi: 10.1186/1471-2350-15-63. PubMed PMID: 24885342; PubMed Central PMCID: PMC4051386.
  16. Haupt J, Deichsel A, Stange K, Ast C, Bocciardi R, Ravazzolo R, Di Rocco M, Ferrari P, Landi A, Kaplan FS, Shore EM, Reissner C, Seemann P. ACVR1 p.Q207E causes classic fibrodysplasia ossificans progressiva and is functionally distinct from the engineered constitutively active ACVR1 p.Q207D variant. Hum Mol Genet. 2014 Oct 15;23(20):5364-77. doi: 10.1093/hmg/ddu255. Epub 2014 May 22. PubMed PMID: 24852373; PubMed Central PMCID: PMC4168825.
  17. Rusmini M, Griseri P, Matera I, Pontarini E, Ravazzolo R, Mavilio D, Ceccherini I. Expression variability and function of the RET gene in adult peripheral blood mononuclear cells. J Cell Physiol. 2014 Dec;229(12):2027-37. doi: 10.1002/jcp.24660. PubMed PMID: 24777754.
  18. Giacopelli F, Cappato S, Tonachini L, Mura M, Di Lascio S, Fornasari D, Ravazzolo R, Bocciardi R. Identification and characterization of regulatory elements in the promoter of ACVR1, the gene mutated in Fibrodysplasia Ossificans Progressiva. Orphanet J Rare Dis. 2013 Sep 18;8:145. doi: 10.1186/1750-1172-8-145. PubMed PMID: 24047559; PubMed Central PMCID: PMC4015442.
  19. Sondo E, Scudieri P, Tomati V, Caci E, Mazzone A, Farrugia G, Ravazzolo R, Galietta LJ. Non-canonical translation start sites in the TMEM16A chloride channel. Biochim Biophys Acta. 2014 Jan;1838(1 Pt B):89-97. doi: 10.1016/j.bbamem.2013.08.010. Epub 2013 Aug 28. PubMed PMID: 23994600; PubMed Central PMCID: PMC3898931.
  20. Sanna-Cherchi S, Sampogna RV, Papeta N, Burgess KE, Nees SN, Perry BJ, Choi M, Bodria M, Liu Y, Weng PL, Lozanovski VJ, Verbitsky M, Lugani F, Sterken R, Paragas N, Caridi G, Carrea A, Dagnino M, Materna-Kiryluk A, Santamaria G, Murtas C, Ristoska-Bojkovska N, Izzi C, Kacak N, Bianco B, Giberti S, Gigante M, Piaggio G, Gesualdo L, Kosuljandic Vukic D, Vukojevic K, Saraga-Babic M, Saraga M, Gucev Z, Allegri L, Latos-Bielenska A, Casu D, State M, Scolari F, Ravazzolo R, Kiryluk K, Al-Awqati Q, D'Agati VD, Drummond IA, Tasic V, Lifton RP, Ghiggeri GM, Gharavi AG. Mutations in DSTYK and dominant urinary tract malformations. N Engl J Med. 2013 Aug 15;369(7):621-9. doi: 10.1056/NEJMoa1214479. Epub 2013 Jul 17. PubMed PMID: 23862974; PubMed Central PMCID: PMC3846391.

Principali linee di ricerca

  • Molecular Genetic studies of rare genetic disorders
  • High throughput screening of chemical compounds

Settore ERC del gruppo

LS2 Genetics, Genomics, Bioinformatics and Systems Biology

Componenti

Cognome Nome Dipartimento di afferenza Qualifica Settore
Ravazzolo Roberto DINOGMI Professore Ordinario MED 03
Puliti Aldamaria DINOGMI Ricercatore MED 03

Altro personale

  • Bocciardi Renata, ricercatore DINOGMI
  • Francesca Giacopelli, assegnista DINOGMI
  • Laura Tonachini, assegnista DINOGMI
  • Serena Cappato, assegnista DINOGMI

Collaborazioni

  • Prof. Peter ten Dijke, Leiden University Medical Center, The Netherlands
  • D. Riccardi: School of Biosciences, University, Cardiff, UK
  • Prof Eileen M. Shore, University of Pennsylvania, Philadelphia, USA
  • Prof. Silvia Brunelli: University of Milano-Bicocca
  • Prof. Giorgio Casari: San Raffaele Scientific Institute, Milano

Finanziamenti

TELETHON Grant to Roberto Ravazzolo: New treatment strategies for Fibrodysplasia Ossificans Progressiva