Key words: Genomic/Genetic instability; ATM Gene therapy; Animal models;

Genomic instability is a key event of cancer. To preserve genomic stability cells have developped systems to detect and repair DNA double strand breaks (DSBs).DSBs occur in response to exogenous agents, such as chemoterpeutics and during physiological processes as during normal DNA replication, meiotic recombination and lymphocytes maturation. If DSBs are not promptly repaired can be substrates for aberrant chromosomal translocations, which promote cancer.The focus of our research is to restore the function of ATM (Ataxia Telangiectasia Mutated) kinase that through an elaborate signal transduction system, has been established as a central player in DNA DSBs repair and genomic integrity preservation.

Ataxia Telangiectasia (A-T) is an inherited disease caused by a fault in the ATM gene that ultimately leads to death before the forties. The disease affects several body systems and causes neurodegeneration, immunodeficiency, sterility, radiosensitivity, lymphomas and leukemia predisposition. Moreover, missense mutations in ATM kinase domain are also found in many type of cancers, such as leukemia, lymphomas, breast, pancreas and gastric cancers but their impact on ATM function and implications for cancer therapy are largely unknown.

We aim to insert a correct version of ATM gene by lentiviral transduction and to edit ATM point mutations by the CRISPR/CAS9 strategy in human A-T cell lines and hematopoietic progenitor cells of ATM defective mouse models. Re-establishing ATM expression, we expect the rescue of immunological defects and the delay/prevention of thymoma in ATM deficient mice. Moreover, we expect to understand the specific role of ATM kinase activity and its essential targets indispensable for genomic stability maintenance.

Education

• Oct 2011-Sep 2012 postdoctoral position –in cardiovascular field at Sapienza University, Rome, Italy.
• Jun 2007-Jun 2011 postdoctoral position –in Microgravity, germ cells, DNA damage field at Sapienza University, Rome, Italy.
• Jun 2004-May 2007 visiting fellowship Post doc position – in genomic stability and DNA repair field at NCI-NIH, Bethesda, MD, USA.
• Nov 2003-May 2004 Assegno di ricerca –spermatogenesis at Tor Vergata University, Rome, Italy.
• Nov 1999-Oct 2003 PhD in Medical Embriology –Spermatogenesis field at Tor Vergata University, Rome, Italy.
• May 1999-Oct 1999 fellowship – cellular biology, toxicology field at Tor Vergata University, Rome, Italy.
• Dec 1996-Mar 1997 fellowship – molecular biology field at Imperial College School, St. Mary’s hospital, London, UK.
• Oct 1991-Oct 1996 Doctor degree in Biological Sciences – Biochemistry field at University of Perugia, Italy.

Positions

• Apr 2015-Today Researcher with permanent position (Ricercatore III livello) at IBBC-CNR, Monterotondo Scalo, Rome, Italy
• Feb 2014-Feb 2017 PI for a Unit PRIN2012 prot 2012227FLF at University of Molise, Campobasso, Italy
• Oct 2012-Mar 2015 Fixed-term researcher at University of Molise, Campobasso, Italy
• Nov 2009-Nov 2012 PI MFG8904 at Tor Vergata University, Rome, Italy.
• Oct 2011-Oct 2012 Teaching Histology and Embriology as Expert of the subject at University of Molise, Campobasso, Italy

Honours/Awards:

• 01 Sep 2006 NIH FARE Award” “Autophosphorylation at Serine 1987 is dispensable for murine Atm activation in vivo”.
• Dec 1996: Leonardo da Vinci Award for working on the ornitine transcarbamilase gene in Cystic Fibrosis.
• Matriculation with Honour in Biological Sciences at the University of Perugia with a thesis title: “A zinc ion-dependent p-nitrophenylphosphatase from bovine liver: purification, characterization and preparation of an antiserum”. 

Researchers:

• Sabrina Putti 
  06-90091-333 |  sabrina.putti@cnr.it
• Tiziana Orsini
  06-90091-334 | tiziana.orsini@cnr.it    

Post doc

• Matilde Merolle

Fellows

• Martina Giangreco

2021 Fondo Europeo per lo Sviluppo Regionale- Regione Lazio- Lazioinnova-POR 2014-2020- A0375-2020-36524 SITeG. Strategies to Implement Glioblastoma Therapy”

2019 ANAT (PI). Title: Gene therapy for Ataxia Telangiectasia syndrome. https://www.associazione-at.it/associazione-nazionale-at/ 

2019 IG grant of AIRC, Project Code: 23329 (PI). Title: Gene therapy for Ataxia Telangiectasia syndrome and for cancer-associated ATM kinase mutations. https://www.airc.it/

2012 PRIN MIUR, Project code: 2012227FLF (Unit). Title: MUSKENDO https://prin.miur.it

2009 MFG grant of AIRC, Project code: 8904 (PI). Title: Relationship between DNA damage and signalling revealed in mouse model of Ataxia Telangiectasia. https://www.airc.it/