Research: The autophagic process: investigating the role of microtubules and tubulin acetylation
FRANCESCA ROMANA PELLEGRINI
Title of the research project: “Exploring the role of Alpha-tubulin N-acetyltransferase 1 (ATAT1) in cancer autophagy: from molecular mechanism to therapeutic targets.”
Thematic area: Molecular Biology
SSD: BIO/11
Education:
• 2021 - Ongoing: PhD in Life Sciences at the University "La Sapienza" of Rome under the supervision of Dr. Daniela Trisciuoglio. Activity performed: Study of the role of the enzyme ATAT1 (Alpha-tubulin N-acetyltransferase 1) in lung cancer.
• Master's degree in Genetics and Molecular Biology, Italian curriculum (LM-06), Faculty of Mathematical, Physical and Natural Sciences at the University "La Sapienza" of Rome obtained on 20.10.2021 with a grade of 110/110 cum laude, discussing the experimental thesis entitled "Characterization of a molecule with antitumor activity: cellular mechanisms that promote autophagy and their role in cell death." Supervisor: Dr. Francesca Degrassi
• Bachelor's degree in Biological Sciences, from the University "La Sapienza" of Rome obtained on 03/21/2019 with a 95/110 grade, discussing the thesis entitled "Cryopreservation techniques for oocytes and embryos: implications in assisted reproduction techniques". External supervisor: Veronica Corsetti; Internal supervisor: Prof. Ada Maria Tata
• Classical high school diploma, from Liceo Classico "Dante Alighieri," Rome (RM), obtained in 2015.
Professional and research experience:
• June 2021 - ongoing: Fellowship at the Institute of Molecular Biology and Pathology (IBPM) of the CNR, on a project entitled "Exploring the role of Alpha-tubulin N-acetyltransferase 1 in cancer: from molecular mechanisms to therapeutic targets" - funded by AIRC (Italian Association for Cancer Research) - cod. IG 2020 #24942 - scientific head and fund holder Dr. Daniela Trisciuoglio.
• Occasional collaborative contract at the Institute of Molecular Biology and Pathology (IBPM) of CNR, on a project entitled "Dynamic signaling reciprocity shapes invadopodia function and metastatic process of ovarian cancer: role of endothelin-1" - funded by AIRC (Italian Association for Cancer Research) - IG code 2018 Id. 21372 3rd year 2021 - scientific responsible and fund holder Dr. Laura Rosanò. NOTICE NO. 4/2021. Activity performed: participation in experimental procedures based on the use of ovarian primary cell cultures, fluorescence microscopy and cytofluorimetry for the analysis of expression and activation of cytoskeleton proteins in relation to the interaction of signals between endothelin receptor and integrin beta1 in the metastatic process of ovarian carcinoma.
• September 2020 - October 2021: Training internship for the preparation of experimental thesis in Genetics and Molecular Biology at the Institute of Molecular Biology and Pathology (IBPM) of CNR, Rome, at the laboratory of Dr. Francesca Degrassi. Activity performed: Study of small molecules with possible antitumor activity, which induce cell death by inhibiting proper fusion between autophagosomes and lysosomes resulting in blockade of autophagic flux.
Brief description of PhD project:
A growing body of evidence suggests that actin cytoskeleton dynamics and microtubules play a key role in autophagy. Autophagy is a highly conserved mechanism in all eukaryotes, used to degrade and recycle various cellular constituents. In recent years, a direct involvement of post-translational modifications of tubulin, including tyrosination and acetylation, has been discovered in the regulation of the autophagic process. However, the role of ATAT1 enzyme, which is responsible for tubulin acetylation on lysine 40 residue on the alpha chain of tubulin, in this field is still completely unexplored. This project aims to investigate the role of ATAT1 acetyltransferase in the autophagic process and how its involvement may influence tumor progression and aggressiveness.
Abstracts and conference participations
• Francesca Romana Pellegrini, A. Iuzzolino, F. Ambrosio, M. Pierrettori, A. Paone, S. Rinaldo, F. Crutruzzolà, F. Degrassi, V. Stagni, D. Trisciuoglio. ATAT1, α-Tubulin N-acetyltransferase 1, promotes autophagy and oxidative stress in non-small cell lung cancer cell lines. The Biennial Congress of the Italian Association of Cell Biology and Differentiation, ABCD 2023. POSTER
• Pellegrini FR, Fianco G, De Martino S, Ventura I, Valente D, Fiore M, Trisciuoglio D, Degrassi F. Blockage of autophagosome-lysosome fusion through SNAP29 inhibition promotes apoptosis in cancer cells. 62nd annual Meeting of the Italian Cancer Society Venice, November 16-18, 2022. POSTER
• Pellegrini FR, De Martino S, Ventura I, Fiore M, Trisciuoglio D, Degrassi F. Blockage of autophagosome-lysosome fusion through SNAP29 inhibition promotes apoptosis via ROS production. 2021 CNR-DSB Conference on “Target discovery for unmet medical needs and precision/ personalized medicine” nella sessione Targets identification in oncology. POSTER
Courses attended:
• June 2021 - July 2021: Online training course "Seeing is believing: school of microscopy - Researcher's Edition" Fondazione Golinelli"
• Technical innovations in basic and translational research: applications to immunology-oncology – 11/2021
• Preparing artworks for scientific papers PhD Course – 05/2022
• Bioinformatic course PhD Life Sciences 01/2023
• Microscopy course PhD Life Sciences 01/2023
• Microscopy course PhD Genetics and Molecular Biology “Imaging 3D cellular models for biomedical applications” 10/2023
Other products of the research:
• Online published CellProfiler pipeline (https://cellprofiler.org/published-pipelines#:~:text=CellProfiler%20enables%20reproducible%20research%20because,CellProfiler%20used%20to%20create%20them.)
The list of publications:
• Fiorentino F; Sementilli S; Menna M; Turrisi F; Tomassi S; Pellegrin FR; Iuzzolino A; D'Acunzo F; Feoli A; Wapenaar H; Taraglio S; Fraschetti C; Del Bufalo D; Sbardella G; Dekker F; Paiardini A; Trisciuoglio D; Mai A; Rotili D. "First-in-Class Selective Inhibitors of the Lysine Acetyltransferase KAT8" Journal of Medicinal Chemistry. Accepted manuscript (Manuscript ID: jm-2022-01937g.R1)
• Pellegrini FR, De Martino S, Fianco G, Ventura I, Valente D, Fiore M, Trisciuoglio D, Degrassi F. Blockage of autophagosome-lysosome fusion through SNAP29 O-GlcNAcylation promotes apoptosis via ROS production. Autophagy. 2023;1-16. doi:10.1080/15548627.2023.2170962
• Nowak RP, Tumber A, Hendrix E, Ansari MSZ, Sabatino M, Antonini L, Andrijes R, Salah E, Mautone N, Pellegrini FR, Simelis K, Kawamura A, Johansson C, Passeri D, Pellicciari R, Ciogli A, Del Bufalo D, Ragno R, Coleman ML, Trisciuoglio D, Mai A, Oppermann U, Schofield CJ, Rotili D. First-in-Class Inhibitors of the Ribosomal Oxygenase MINA53. J Med Chem. 2021 Dec 9;64(23):17031-17050. doi: 10.1021/acs.jmedchem.1c00605. Epub 2021 Nov 29. PMID: 34843649; PMCID: PMC8667043.