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Giovanna Grimaldi

Research Focus: Endogenous ADP-ribosylation

Group  leader : Daniela Corda

Within Daniela Corda's laboratory, my specific interest is to understand the physiological and pathological role of mono-ADP-ribosylation, by investigating the enzymes and the substrates involved in this post-translational modification, along with their regulation. The main projects can be summarised as follow:

1. study of mono-ADP-ribosyltransferases of the PARP family (PARP6-16);

2. study of the BFA-mediated ADP-ribosylation of CtBP/BARS;

3. study of the mechanism of action of some bacterial toxins (e.g. NarE).

 

1. Study of mono-ADP-ribosyltransferases of the PARP family

We have started to characterize the localization and function of PARPs using antibody staining, RNAi and biochemical approches for the identification of their physiological substrates. The data obtained so far suggested that some of these PARPs are involved in diverse cellular functions, ranging from the regulation of small-GTPases to the control of RNA as well as to the regulation of cell cycle progression, with particular emphasis on mitosis.

 

2. Study of the BFA-mediated ADP-ribosylation of CtBP/BARS

In addition to this aspect, our laboratory has focused and defined a new mechansim of ADP-ribosylation catalysed by the ADP-ribosyl cyclase CD38 and the fungal toxin BFA; this reaction is exquisitely selective for the CtBP1/BARS protein and causes the inhibition of its activity required for mitotic progression, with important implications for treatment of tumors characterized by high levels of CD38.

 

3. Study of the mechanism of action of bacterial toxins

This project is based on the identification and study of ADP-ribosylated substrates by  the bacterial toxins that cause human disfunctions, with the aim to find druggable molecular targets.

 

Based on this information, we aim to determine pathways in which mono-ADP-ribosylation is involved and, if altered, how it can be connected to human diseases.

Curriculum

Personal data

Born : 03/02/1982 in Venosa (PZ), Italy
Citizenship : Italian 

Scientific carrier

2014 at present:               researcher position at the CNR Institute of Protein Biochemistry (CNR-IBP);
2012-May 2014:post-doc position at the CNR-IBP Institute;
2009-2011:fellowship from the Italian Federation for Cancer Research (FIRC, Milan, Italy);
Oct 2007- Dec 2008:doctoral fellowship at Mario Negri Sud Institute, Department of Cell Biology;
April 2007- Sept 2007:pre-Doctoral Fellowship Mario Negri Sud Institute, Department of cell  biology;
Sept 2006- March 2007:co-co-co contract at the University of Florence, Department of Clinical  Physiology.

 

Education

February 2012: Open University PhD. Project: Identification and roles of intracellular substrates of mono-ADP-ribosylation. Supervisor: Dr Daniela Corda.

July 2006: Masters in Medical Biotechnology, University of Florence, Italy Thesis: Role of the tyrosine kinase FAK in the repulsive response mediated by ephrinA1. (110/110, with honours).

Sept 2004: Degree in Biotechnology, University of Florence, Italy Thesis: Interaction between the Eph receptor and the low molecular weight tyrosine phosphatase LMW-PTP. Effects on the repulsive response. (110/110, with honours)


Awards 

  • 3 year Fellowship from the Italian Federation for Cancer Research (FIRC, Milan, Italy).
    Winners of several Young Travel Grants (YTG):
  • July 2009: YTG for the 34th FEBS Congress on Life’s Molecular Interaction, Prague.
  • September 2009: EMBO FEBS YTG for a Summer School on “Proteins and their Networks – from specific to global analysis”. Spetsai.
  • June 2010: YTG for the 10th Young Scientist Forum and 35th FEBS Congress on Molecules of Life, Gothenburg.

 

Publications 

  • From toxins to mammalian enzymes: the diversity of mono-ADP-ribosylation. Grimaldi G, Corda D., Catara G.  2015 Front Biosci (Landmark Ed). 20:389-404.
     
  • Colanzi A*Grimaldi G*, Catara G, Valente C, Cericola C, Liberali P, Ronci M, Lalioti VS, Bruno A, Beccari AR, Urbani A, De Flora A, Nardini M, Bolognesi M, Luini A, Corda D. Molecular mechanism and functional role of brefeldin A-mediated ADP-ribosylation of CtBP1/BARS. PNAS 2013, 110(24): 9794-99. * These authors contributed equally to the work.
     
  • Giannoni E, Buricchi F, Grimaldi G, Parri M, Cialdai F, Raugei G, Ramponi G, Chiarugi P.Redox regulation of anoikis: reactive oxygen species as essential mediators of cell survival. Cell Death Differ. 2008, 15, 867-78.
     
  •  Buricchi F, Giannoni E, Grimaldi G, Parri M, Raugei G, Ramponi G, Chiarugi P. Redox regulation of ephrin/integrin cross-talk. Cell Adhes. Migrat. 2007, 1, 33-42.
     
  • Parri M, Buricchi F, Giannoni E, Grimaldi G, Mello T, Raugei G, Ramponi G, Chiarugi P.Ephrina1 activates a Src/Fak-mediated motility response leading to disruption of cell-cell adhesion and to activation of actinomyosin contractility. J. Biol. Chem. 2007, 282, 19619-28.