Patrizia Zavattari

 

Department of Biomedical SciencesZavattari

Telephone: +39 0706754101

E-mail: pzavattari@unica.it

Personal web page: here

Principal areas of expertise: Genomic variability; Epigenetics

 

 


Identification of genetic and epigenetic alterations in cancer and genetic diseases and their relationship with environmental factors

Our laboratory has gained expertise in searching for disease genes alterations and environmental factors, both in multifactorial diseases, such as cancer and autoimmunity, and Mendelian genetic diseases. Understanding the molecular mechanisms of genetic and epigenetic disorders, from genome to transcriptome to proteome to epigenome, will result in an efficient diagnosis and better definition of prognostic and predictive markers. In carrying out our research projects we apply various methods of molecular biology and molecular genetics ranging from search for mutations by next generation sequencing, genotyping using fluorescence-based techniques, quantitation of nucleic acids using fluorescent probes, and the study of CpG loci methylation status. Furthermore, we have just begun to acquire the skills for genome and epigenome editing experiments using CRISPR CAS9 on 2D and organoid cell lines, which could lay the foundations for therapeutic interventions of epigenetic reprogramming. In the last decade, our laboratory has followed the rapid development of biotechnology and then exploited the availability of NGS and array-based platforms that allow the massive simultaneous genotyping of millions of polymorphic markers, the quantization of the entire transcriptome and the study of genetic and epigenetic alterations extended to the whole genome/methylome. This has also led to the growth of our staff in bioinformatics and biostatistics which are instrumental for a correct interpretation of the extensive data resulting from the analysis of the genome, transcriptome and epigenome.

Within this general line of research, specific projects are:

  1. Identification of epigenetic and genetic changes underlying pathways involved in the development of human cancer. Study of functional mechanisms and research of biomarkers using non-invasive techniques.
  2. Identification of molecular defects underlying Autism Spectrum Disorders and rare genetic diseases.
  3. Study of environmental factors possibly influencing the onset of complex multifactorial diseases.

Key publications:

A:

  1. Fadda A*, Gentilini D*, Moi L*, Barault L, Leoni VP, Sulas P, Zorcolo L, Restivo A, Cabras F, Fortunato F, Zavattari C, Varesco L, Gismondi V, De Miglio MR, Scanu AM, Colombi F, Lombardi P, Sarotto I, Loi E, Leone F, Giordano S, Di Nicolantonio F, Columbano A, Zavattari P*. Colorectal cancer early methylation alterations affect the crosstalk between cell and surrounding environment, tracing a biomarker signature specific for this tumor. Int J Cancer. 2018 Aug 15;143(4):907-920. doi: 10.1002/ijc.31380. Epub 2018 Apr 6.
  2. Barault L, Amatu A, Siravegna G, Ponzetti A, Moran S, Cassingena A, Mussolin B, Falcomatà C, Binder AM, Cristiano C, Oddo D, Guarrera S, Cancelliere C, Bustreo S, Bencardino K, Maden S, Vanzati A, Zavattari P, Matullo G, Truini M, Grady WM, Racca P, Michels KB, Siena S, Esteller M, Bardelli A, Sartore-Bianchi A, Di Nicolantonio F. Discovery of methylated circulating DNA biomarkers for comprehensive non-invasive monitoring of treatment response in metastatic colorectal cancer. Gut. 2018 Nov;67(11):1995-2005. doi: 10.1136/gutjnl-2016-313372. Epub 2017 Oct 5.
  3. Antonelli M*, Fadda A*, Loi E, Moi L, Zavattari C, Sulas P, Gentilini D, Cameli C, Bacchelli E, Badiali M, Arcella A, Morra I, Giangaspero F, Zavattari P*. Integrated DNA methylation analysis identifies topographical and tumoral biomarkers in pilocytic astrocytomas. Oncotarget. 2018 Feb 12;9(17):13807-13821. doi: 10.18632/oncotarget.24480. eCollection 2018 Mar 2.
  4. Vega-Benedetti AF*, Loi E*, Moi L, Blois S, Fadda A, Antonelli M, Arcella A, Badiali M, Giangaspero F, Morra I, Columbano A, Restivo A, Zorcolo L, Gismondi V, Varesco L, Bellomo SE, Giordano S, Canale M, Casadei-Gardini A, Faloppi L, Puzzoni M, Scartozzi M, Ziranu P, Cabras G, Cocco P, Ennas MG, Satta G, Zucca M, Canzio D, Zavattari P*. Clustered protocadherins methylation alterations in cancer. Clin Epigenetics. 2019 Jul 9;11(1):100. doi: 10.1186/s13148-019-0695-0.
  5. Saffari A, Silver MJ, Zavattari P, Moi L, Columbano A, Meaburn EL, Dudbridge F. Estimation of a significance threshold for epigenome-wide association studies. Genet Epidemiol. 2018 Feb;42(1):20-33. doi: 10.1002/gepi.22086. Epub 2017 Oct 15.
  6. Loi E, Moi L, Fadda A, Satta G, Zucca M, Sanna S, Amini Nia S, Cabras G, Padoan M, Magnani C, Miligi L, Piro S, Gentilini D, Ennas MG, Southey MC, Giles GG, Wong Doo N, Cocco P, Zavattari P*. Methylation alteration of SHANK1 as a predictive, diagnostic and prognostic biomarker for chronic lymphocytic leukemia. Oncotarget. 2019 in press.
  7. Zavattari P**, Perra A**, Menegon S*, Kowalik MA, Petrelli A, Angioni MM, Follenzi A, Quagliata L, Ledda-Columbano GM, Terracciano L, Giordano S, Columbano A. Nrf2, but not β-catenin, mutation represents an early event in rat hepatocarcinogenesis. 2015 Sep;62(3):851-62. doi: 10.1002/hep.27790. Epub 2015 Apr 22.

B:

  1. Bacchelli E*, Loi E*, Cameli C*, Moi L, Vega-Benedetti AF, Blois S, Fadda A, Bonora E, Mattu S, Fadda R, Chessa R, Maestrini E, Doneddu G, Zavattari P*. Analysis of a Sardinian Multiplex Family with Autism Spectrum Disorder Points to Post-Synaptic Density Gene Variants and Identifies CAPG as a Functionally Relevant Candidate Gene. J Clin Med. 2019 Feb 7;8(2). pii: E212. doi: 10.3390/jcm8020212.

C:

  1. Valera P*, Zavattari P*, Albanese S, Cicchella D, Dinelli E, Lima A, De Vivo B. A correlation study between multiple sclerosis and type 1 diabetes incidences and geochemical data in Europe. Environ Geochem Health. 2014 Feb;36(1):79-98. doi: 10.1007/s10653-013-9520-4. Epub 2013 Apr 9.
  2. Valera P**, Zavattari P**, Sanna A, Pretti S, Marcello A, Mannu C, Targhetta C, Bruno G, Songini M. Zinc and Other Metals Deficiencies and Risk of Type 1 Diabetes: An Ecological Study in the High Risk Sardinia Island. PLoS One. 2015 Nov 11;10(11):e0141262. doi: 10.1371/journal.pone.0141262. eCollection 2015.
  3. Sanna A, Firinu D, Zavattari P*, Valera P*. Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis. Nutrients. 2018 Jan 11;10(1). pii: E68. doi: 10.3390/nu10010068. Review.
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