Projects

IDH1/2 mutation inhibition in lower grade gliomas: from preclinical models to clinical applications
2024-2026 | Next Generation EU PNRR 2023

Ferdinando Di Cunto, Operative Unit Leader
Prof. Roberta Rudà, Division of Neuro-Oncology, Department of Neuroscience “Rita Levi Montalcini”, University of Turin,  Italy
Our group participates in this project by virtue of the expertise acquired in the analysis of brain tumors using in vitro and in vivo models. The project is coordinated by Prof. Roberta Rudà (Department of Neuroscience – University of Turin) and thanks to a collaborative network that includes the Federico II University of Naples, the potential efficacy of the combination of the drug vorasidenib and pharmacological compounds that influence DNA and histone methylation in the therapy of brain tumors is explored.

Dissection of common mechanisms in genetic primary microcephaly.
2023-2025 | Project PRIN 2022, funded by MIUR through the Next Generation EU program

Ferdinando Di Cunto, Principal Investigator
Primary microcephaly (MCPH) is a disabling condition characterized by a reduced number of neurons, resulting from the alteration of the delicate balance between proliferation, differentiation and death that characterizes brain development. This condition can be due to the mutation of at least thirty different genes, and many more genes are involved in clinical forms in which microcephaly represents only one of the main features of more complex syndromes. In this project, based on a close collaboration with the research groups of PatriziaSomma (CNR-Rome) and Laura Ciapponi (University of Rome – Sapienza) we are exploring the possible common mechanisms of MCPH, using Drosophila and mammalian mutants, as well as in vitro models, including human cerebral organoids. Our working hypothesis is that, in the developing brain, the proteins encoded by MCPH genes are necessary for interconnected functions, such as maintaining genome stability, ensuring a precise temporal order of gene expression and maintaining a correct balance in cell fate. The final aim of the project is to identify new prognostic markers and highlight possible therapeutic strategies.

Development of Citron Kinase as a therapeutic target for brain tumors.
2019-2024 | Italian Association for Cancer Research (AIRC)

Ferdinando Di Cunto, Principal Investigator
Citron Kinase (CITK) protein is the product of a gene implicated in a severe form of microcephaly (MCPH17). During normal development, its absence severely damages nerve cell progenitors, altering their proliferation and leading to the activation of programmed cell death processes. Starting from this basis, thanks to gene inactivation studies conducted in mouse models and human cell lines, we discovered that CITK is also essential for the proliferation of tumor cells, particularly in medulloblastomas, aggressive brain tumors that mainly affect the cerebellum and children. On this basis, in collaboration with the Experimental Therapy Group of the IFOM Institute in Milan (Dr. Ciro Mercurio) and with the company AXXAM, we have developed a project for the identification of molecules capable of determining an inhibition of the enzymatic activity of CITK and for the evaluation of their antitumor activity.

The IFOM ETS group contributed to the project by providing a library of 10.000 compounds characterized by a high probability of being protein kinase inhibitors. The collaborators are also involved in lead optimization, through synthesis of compounds derived from the structure of the most promising hits.