Signalling and Molecular Interactions in Life Events (SMILE) Lab
Keywords: Breast cancer biology, PARP enzymes, mono-ADP-ribosylation, viral infection, innate immune signalling, patient-derived organoids, spheroids, targeted therapies
Group leader: Giovanna Grimaldi
Contacts:
Phone: +39 0816132578
Email:giovanna-grimaldi@cnr.it
Our group is interested in how mono-ADP-ribosylation (MARylation) regulates cellular adaptation in health and disease, with a focus on its roles in breast cancer progression and in host antiviral defence in collaboration with virology experts. Our research program is organized around two main lines of investigation.
The first line, within our AIRC-funded project, examines how MARylation and PARP12 modulate pathways involved in cell survival, proliferation, DNA damage repair, response to endocrine therapies, and activation of innate-immune programs that sustain tumour aggressiveness. We aim to elucidate how PARP12-driven MARylation reshapes cancer cell behaviour and to uncover vulnerabilities that can be targeted to overcome hormone therapy resistance, integrating molecular studies, advanced imaging, functional assays, and 3D models.
The second line, as part of the PNRR-funded INF-ACT project, explores the role of MARylation in host antiviral immunity, investigating how it influences viral entry, modifies cellular and viral substrates, and contributes to virus-induced cytopathogenicity, with the goal of identifying mechanisms to limit infection or mitigate disease severity.
To achieve these objectives, we combine advanced imaging, RNA profiling, proteomics, and bioinformatics with classical biochemical and cell-based assays, CRISPR-based genetic engineering, and 3D culture systems.
Our long-term vision is to map MARylation-dependent pathways and develop selective small-molecule inhibitors and complementary molecular tools, bridging fundamental insights with therapeutic innovation in both cancer and antiviral research.
- Pavithran A, Morone B, Filograna A, Matarese M, Lo Monte M, Dathan NA, Corda D, Grimaldi G. PARP12-mediated ADP-ribosylation contributes to breast cancer cell fate by regulating Akt activation and DNA-damage response. Cell Mol Life Sci. 2025 Jan 23;82(1):58. doi: 10.1007/s00018-025-05586-z.
- Morone B, Grimaldi G. PARP enzymes and mono-ADP-ribosylation: advancing the connection from interferon-signalling to cancer biology. Expert Rev Mol Med. 2024 Aug 27;26:e17. doi: 10.1017/erm.2024.13.
- Di Paola S, Matarese M, Barretta ML, Dathan N, Colanzi A, Corda D, Grimaldi G. PARP10 Mediates Mono-ADP-Ribosylation of Aurora-A Regulating G2/M Transition of the Cell Cycle. Cancers (Basel), 2022, 14(21):5210. doi: 10.3390/cancers14215210
- Grimaldi G, Filograna A, Schembri L, Lo Monte M, Di Martino R, Pirozzi M, Spano D, Beccari AR, Parashuraman S, Luini A, Valente C, Corda D. PKD-dependent PARP12-catalyzed mono-ADP ribosylation of Golgin-97 is required for E-cadherin transport from Golgi to plasma membrane. Proc Natl Acad Sci U S A. 2022; 119(1).
- Grimaldi G, Catara G, Palazzo L, Corteggio A, Valente C, Corda D. PARPs and PAR as novel pharmacological targets for the treatment of stress granule-associated disorders. Biochem Pharmacology. 2019; 167: 64-75.
- Grimaldi G and Corda D. ADP-ribosylation and intracellular traffic: an emerging role for PARP enzymes. Biochem Soc Trans. 2019 Feb 28;47(1):357-370.
- Catara G*, Grimaldi G*, Schembri L, Spano D, Turacchio G, Lo Monte M, Beccari AR, Valente C, Corda D. PARP1-produced poly-ADP-ribose causes the PARP12 translocation to stress granules and impairment of Golgi complex functions. Sci Rep. 2017 Oct 25;7(1):14035. *These authors contributed equally to this work.
- Colanzi A*, Grimaldi G*, Catara G, Valente C, Cericola C, Liberali P, Ronci M, Lalioti VS, Bruno A, Beccari A, Urbani A, DeFlora A, Nardini M, BolognesiM, Luini A, Corda D. Molecular mechanism and functional role of brefeldin-A-mediated ADP-ribosylation of CtBP1/BARS. Proc Natl Acad Sci U S A. 2013; 110(24): 9794-9. *These authors contributed equally to this work.
Research group
Post-doc fellow: Nadia Badolati (nadiabadolati@cnr.it)
PhD Student(s): Ludovica Serpieri (ludovicaserpieri@cnr.it)
Currently recruiting: 1 post-doctoral researcher and 1 post-graduate research fellow.
Jul 2023 – Present: Principal Investigator of the project “Overcoming Breast Cancer Resistance to Hormone-Based Therapy by Targeting the PARP12 Enzyme,” funded by the Italian Association for Cancer Research (AIRC). SIS IG_28688, 5-year grant (Jul 2023 – Jun 2028).
Nov 2022 – Present: Head of the Research Unit and CNR Representative for Spoke 1-affiliated Institutes within the PNRR project “One Health Basic and Translational Research Actions Addressing Unmet Needs on Emerging Infectious Diseases,” funded by the European Community. This is a 3-year multicenter project (Nov 2022 – Oct 2025).
Jun 2018 – Oct 2024: Co-coordinator of the Second Unit: Progetto Ricerca Finalizzata (under 40) from Ministry of Health GR-2018-12367517_Pharmacological targeting of CtBP1/BARS in cancer.
Scientific Coordinator of the following projects (Departmental Funds):
Jul 2022-present: Scientfic Coordinator of the project: “PARP12-dependent mono-ADP-ribosylation controls specific membrane transport routes: a functional and morphological analysis.” (DSB.AD001.242; Prot. IEOS: 3225/2022; 3226/2022).
Jun 2022-present: Scientfic Coordinator of the project “Mechanisms of the Enhanced Inflammatory Responses in Ageing Individuals: INFLAMMAGEING.” (DSB.AD001.239; Prot. 2531/2022; 2532/2022).
Invited Speaker at the AIRC event “AIRC’s Strength in the Territory: The Impact on Cancer Treatment” (June 3, 2024, Teatro Comunale Gerardo Guerrieri, Matera) as a researcher selected for the AIRC SIS grant, in recognition of scientific excellence. Among the other speakers: Andrea Sironi (President of the AIRC Foundation), Federico Caligaris Cappio (Scientific Director of the AIRC Foundation), and Alberto Mantovani (Scientific Director of Humanitas, Emeritus Professor at Humanitas University, and President of the Humanitas Research Foundation).
Invited Speaker at a TED Talk (2024) – Recognition for contributions to scientific dissemination and innovation in the field of biomedicine, with a particular focus on cancer research. (https://www.facebook.com/photo.php?fbid=914144320863155&id=100068027855471&set=a.511532657790992).
https://www.corriere.it/cronache/24_febbraio_13/seno-indaghiamo-sull-enzima-che-sabota-terapie-ormonali-a24d0d42-ca8d-11ee-b875-b42893f88392.shtml
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https://www.medicinaintegratanews.it/e-caderina-manca-il-contatto-ed-e-patologia/
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https://www.medicinaintegratanews.it/e-caderina-manca-il-contatto-ed-e-patologia/
https://www.italpress.com/unalterazione-causa-la-perdita-dei-contatti-tra-cellule/
