- Research project: Identification of new drug targets and therapeutic RNA based strategies for cancer therapy
- Thematic area: molecular, cell biology and biochemistry
- SSD: BIO/11
- Brief resume:
Current position: Second year PhD student in Life Sciences, XXXVIII cycle. Department of Biochemical Sciences "A. Rossi Fanelli", University of Rome, La Sapienza
Previous experiences
June- Oct 2022: Pre-doctoral research scholarship, Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome
TUTOR: Prof.ssa Francesca Cutruzzolà
PROJECT: Design and implementation of RNA aptamers for inhibition of metabolic enzymes
2020-2021: Epigenetics Didactic Laboratories Assistant, Sapienza University of Rome
COURSE: Epigenetics, LM Genetics and Molecular Biology
PROF: Lucia Piacentini
March 2019- Jan 2022: Bachelor' and Master's Trainee internship at Department of Biology and Biotechnology "Charles Darwin", Sapienza
University of Rome
TUTOR: Prof.ssa Lucia Piacentini - Laboratory of Epigenetics
THESIS TITLE: "Genetic and functional characterization of the Drosophila melanogaster endoribonuclease CG2145 in glial tissue"
Education
Oct 2019 - Jan 2022: M.Sc degree in Genetics and Molecular Biology - Sapienza University of Rome
Grade: 110/110 cum laude
Sept 2016 - Oct 2019: B.Sc degree in Biological Sciences - Sapienza University of Rome - Genetics and Molecular curriculum
Grade: 110/110 cum laude
- PhD project description: The PhD project is focused on the identification of new therapeutic strategies and new drug targets for tumors, by exploiting the interactions between RNA and proteins and their importance in tumorigenesis. In this regard, we identified as therapeutic target the metabolic enzyme Serine Hydroxmethyltransferase (SHMT) that catalyzes the reversible conversion of serine and tetrahydrofolate into glycine and 5, 10 methylenetetrahydrofolate. SHMT plays a key role in one carbon metabolism, a complex network fueling factors fundamental for highly proliferating cells. It’s no surprise that both cytosolic and mitochondrial isoforms (SHMT1/2) are found overexpressed in different types of tumors, with the SHMT2 isoform related to tumor progression and poor patient prognosis. These observation highlights the potential application of
targeting SHMTs in tumor-targeted therapy, thus providing a novel strategy for cancer treatment. Several attempts have been recently made to develop small molecule inhibitors that target both SHMT1 and SHMT2 due to their high sequence identity, such as 2.12 and SHIN, but no inhibitor successfully used in vivo is currently available suggesting that a completely new approach is needed.
Starting from the demonstration that RNA molecules can efficiently inhibit in vitro both SHMT1 and SHMT2, the aim of this pHD project consists in designing and testing novel small inhibitory RNAs that can target SHMT proteins and optimizing delivery strategies to be employed in an RNA-based therapeutic strategy to treat cancer patients. Through in vitro RNA-protein affinity binding assays different small RNA sequences were selected to be tested for cytotoxic effect analysis on lung adenocarcinoma tumor cells. This involved conducting cell viability assays on six out of the eight 25-50 nucleotide sequences tested for in vitro affinity with the SHMT2 protein. Specifically, the focus was on the sequences that demonstrated binding with the protein in vitro. For the evaluation of tumor cells' inflammatory response: using real-time PCR, an initial assessment was made of how the direct transfection of different RNA sequences affects the activation of the inflammatory response in tumor cells.
Seminars
03/03/23: Engineering Proteins To Boost LTP And Memory - Prof. Cristian Ripoli Department of Neuroscience of Università Cattolica del Sacro Cuore - Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
09/03/23: Application of deep learning to the protein structure prediction: the tale of a “gigantic leap” - Prof. Anna Marabotti, Department of Chemistry and Biology "A. Zambelli" University of Salerno.
17/03/23: Deciphering self-renewal traits in epidermal stem cells - Dott. Elena Enzo Centre for Regenerative Medicine ‘‘Stefano Ferrari’’, University of Modena and Reggio Emilia.
23/03/23: Insulin Signaling in Alzheimer’s Disease Brain and Models Thereof- Prof. Eugenio Barone Department of Biochemical Sciences -Sapienza University.
30/03/23: Educating tutor-associate macrophages under metabolic stress - Dr. Ping-Chih Ho Department of Fundamental Oncology & Ludwig Institute for Cancer Research University of Lausanne, Switzerland
14/04/23: Synthetic Biology: what, why and how - Dott.ssa Velia Siciliano, Synthetic and Systems Biology for Biomedicine Istituto Italiano di Tecnologia-IIT
21/04/23: Protecting our genome: mechanisms to maintain DNA repeats stability in human cells - Prof. Simona Giunta Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Italy
27/04/23: Regulation of enzymatic activity mediated by liquid-liquid phase separation - Dott. Mirco Dindo Department of Medicine and Surgery, Section of Physiology and Biochemistry University of Perugia, 06132 Perugia, Italy
12/05/23: The chaperonin GroEL nano-machine: allostery and function - Prof. Amnon Horowitz Department of Chemical and Structural Biology Weizmann Institute of Science Rehovot, Israel
19/05/23: The axonal transport machinery and its dysfunctions in neurodegenerative diseases - Prof. Giampietro Schiavo Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology Dementia Research Institute, University College London, London
Congresses:
29/03/23: Aptamers 2023 Oxford
05/06/23: 2nd Scientific MOSBRI Conference, Zaragoza (Spain)
21/06/23: Riboregulation from bacteria to eukaryotes: mechanisms and challenges - Sapienza, University of Rome. Invited Speakers: MATTHIAS HENTZE (EMBL, DE), BEN LUISI (UNIVERSITY OF CAMBRIDGE, UK), INA HUPPERTZ (MAX PLANCK, COLOGNE, DE), GIAN GAETANO TARTAGLIA (IIT, IT)
Courses:
30-31/01/2023: From Ramon y Cajal to cryoem course for adavanced microscopy - Silvia d’angelantonio, Egle De Stefano, Giorgio Giardina.
4-11/05/23: Preparing artwork for scientific papers - Prof. Giorgio Giardina (from the Department of Biochemical Sciences “Alessandro Rossi Fanelli”)
16-18/05/23: Biotechnology and Laboratory Safety - Elena Sturchio - Inail, dott.ssa Priscilla Boccia - Inail, dott.ssa Miriam Zanellato - Inail, Technological Innovations department