BIOGRAPHICAL SKETCH NAME Fabrizio d`Adda di

BIOGRAPHICAL SKETCH
NAME
Fabrizio d’Adda di Fagagna
EDUCATION/TRAINING
INSTITUTION AND LOCATION
University of Trieste, Italy.
International School for Advanced Studies
(ISAS-SISSA), Trieste, Italy.
Gurdon Institute, Cambridge University, UK
(Steve Jackson Laboratory).
POSITION TITLE
Tenured Principal Investigator at IFOM Foundation,
Milan, Italy
Group leader (Primo ricercatore) at IGM (National
Research Council), Pavia, Italy
DEGREE
B.S.
Ph.D.
YEAR
1990
1995
Research
associate
2003
FIELD OF STUDY
Biology
Molecular Genetics (HIV-1
transcription)
DNA damage response
and telomere biology in
mammals
A. Personal Statement
I am a cell and molecular biologist that studies the involvement of the DNA damage response (DDR) pathways in
mammals in physiologically relevant processes, mainly aging and cancer.
As a Research Associate in Steve Jackson’s laboratory in Cambridge, UK, I established the involvement of the DDR
machinery in mammalian telomere maintenance (Nature Genetics 1999; Current Biology 2001). I also demonstrated that
replicative cellular senescence is the outcome of the direct recognition of critically-short telomeres by the DDR apparatus
(Nature 2003). Concomitantly, I discovered the evolutionary conservation of mammalian DNA repair factors in prokaryotes
(Science 2002; EMBO Reports 2003) and that DDR components are proteolytically inactivated in apoptosis (MCB 1999;
EMBO Reports 2002, NAR 2003).
As an independent PI at IFOM, Milan, Italy, with my group I demonstrated that oncogene activation is an intrinsically
genotoxic event that, by altering DNA replication, causes DDR activation and cellular senescence (Nature 2006). The
model proposed in this work and in other invited reviews (NRMCB 2007, TCB 2007, NRC 2008, COGD 2009) is generally
perceived as a valuable contribution to the understanding of the events associated with cancer initiation. We also probed
into the mechanisms of oncogene-induced chromatin changes and proposed they are the consequence of DNAreplication stress, they are maintained in cells bypassing cellular senescence including proliferating cancer-tissues, and
play DDR-suppressing functions (Nature Cell Biol 2011).
We also reported that the genomes are not uniformely repairable and, due to evolutionary constrains, telomeres, if
damaged, cannot be repaired, both in vitro and in aging primates (Nature Cell Biol 2012). This allowed to propose a
unifying model (COGD 2014) involving the generation of irreparable DNA damage at telomeres to explain the
establishment of different types of cellular senescence, including the oncogene-induced one (EMBO J. 2012).
Finally, we recently discoveed a previously unanticipated role of non coding RNAs in the direct activation of the DDR at
DNA damage sites (Nature 2012).
B. Qualifications, honors and awards
2014
National Scientific Qualification (Abilitazione) as “Full and Associate University Professor in Medical
Genetics, General Pathology, Clinical Pathology, Molecular Biology, Applied Biology, General and
Clinical Biochemistry, Histology, Genetics and Microbiology”.
2013
ERC Advanced Grant awardee
2012
Marsala Rodriquez Prize on Cancer Research.
2012
Faculty of 1000 (F1000) Faculty member
2012
EMBO member
2009
European Association for Cancer Research (EACR) Young Cancer Researcher Award
2009
Premio Sapio for research in Italy
2007
EMBO Young Investigator Award
1992
Winner of the SIBBM prize for the best graduate thesis in molecular biology of the year in Italy.
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Member of the Scientific Committee of Telethon.
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Member of the EMBO Long Term fellowships committee.
C. Publications
Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular
senescence and ageing. Rossiello F, Herbig U, Longhese MP, Fumagalli M, d'Adda di Fagagna F. Curr Opin Genet Dev.
2014 Aug 4;26C:89-95. doi: 10.1016/j.gde.2014.06.009.
http://www.sciencedirect.com/science/article/pii/S0959437X14000628
A direct role for small non coding RNAs in DNA damage response. d’Adda di Fagagna F. Trends in Cell Biology. 2013
Oct 21. pii: S0962-8924(13)00165-7. doi: 10.1016/j.tcb.2013.09.008.
http://www.cell.com/trends/cell-biology/abstract/S0962-8924(13)00165-7
DNA damage in mammalian neural stem cells leads to astrocytic differentiation mediated by BMP2 signaling through JAKSTAT. Leonid Schneider, Serena Pellegatta, Rebecca Favaro, Federica Pisati, Paola Roncaglia, Giuseppe Testa, Silvia
K. Nicolis, Gaetano Finocchiaro, and Fabrizio d’Adda di Fagagna. Stem Cell Reports, Volume 1, Issue 2, 123-138, 25
July 2013.
http://www.cell.com/stem-cell-reports/abstract/S2213-6711(13)00046-5
Site-specific DICER and DROSHA RNA products control the DNA-damage response. Francia S., Michelini F., Saxena A.,
Anelli V.,Tang D., Dobreva M., Mione M., Carninci P., and d'Adda di Fagagna F. Nature 2012 Aug 9; 488 (7410): 231-5.
http://www.nature.com/nature/journal/v488/n7410/full/nature11179.html
Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Fumagalli M., Rossiello
F., Clerici M., Barozzi S., Spath L., Dobreva M., Herbig U., Beausejour M. C., Longhese M. P., and d'Adda di Fagagna F.
Nature Cell Biology, 2012 Mar 18.
http://www.nature.com/ncb/journal/v14/n4/full/ncb2466.html
Crosstalk between chromatin state and DNA damage response in cellular senescence and cancer. Sulli G., Di Micco R.,
and d’Adda di Fagagna F. Nature Reviews Cancer. 2012 Oct;12(10):709-20.
http://www.nature.com/nrc/journal/v12/n10/full/nrc3344.html
Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer. Di Micco
R., Sulli G., Dobreva M., Liontos M., Botrugno O.A., dal Zuffo R., d’Ario G., Montani E., Mercurio C., Hahn W.C.,
Gorgoulis V., Minucci S. and d'Adda di Fagagna F., Nature Cell Biology, 13, 292–302 (2011).
http://www.nature.com/ncb/journal/v13/n3/full/ncb2170.html
Living on a break: cellular senescence as a DNA damage response. d’Adda di Fagagna F. Nature Reviews Cancer,
2008 Jul; 8(7):512-22.
http://www.nature.com/nrc/journal/v8/n7/full/nrc2440.html
Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Di Micco R., Fumagalli
M., Cicalese A., Piccinin S., Gasparini P., Luise C., Schurra C., Garré M., Nuciforo P., Bensimon A., Maestro R., Pelicci
P.G., and d'Adda di Fagagna F. Nature, 2006; 444: 638-642.
http://www.nature.com/nature/journal/v444/n7119/full/nature05327.html
A DNA damage checkpoint response in telomere-initiated senescence. d'Adda di Fagagna F., Reaper P.M., ClayFarrace L., Fiegler H., Carr P., von Zglinicki T., Saretzki G., Carter N.P. and Jackson S.P. Nature, 2003; 426: 194-198.
http://www.nature.com/nature/journal/v426/n6963/full/nature02118.html
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