Ricerc@Sapienza

Our lab is interested in how genetic and epigenetic alterations impinge on cancer development and progression.

Research projects currently running in the laboratory include:

1. Innovative strategies to target MYC(N)-driven tumors

MYC-driven tumors are aggressive and poorly treatable tumors. Focusing on MYCN-dependent replication stress, we highlighted the relevance of specific DNA repair pathways as vulnerabilities suitable for therapeutic intervention. We are currently investigating on the role of the ATM kinase in coordinating the cellular responses to PARPi-induced replication stress in MYCN-driven environment.

Since oncogenic deregulation of MYC family appears to be associated with severe immune suppression and often with a cold phenotype, additional efforts are dedicated to investigating the molecular mechanisms driving the cold phenotype of MYC(N)-driven tumors, searching for strategies to convert them into hot and more immunogenic tumors.

2. Uncovering non-canonical roles of the Nijmegen Breakage Syndrome protein 1 (NBS1) in cerebellar development and tumorigenesis

While NBS1 is classically recognized as a key player in the DNA damage response, emerging evidence suggests that DNA repair proteins may have unexpected roles in cellular architecture and signaling. Our research focuses on a newly discovered role of NBS1 on primary cilia morphology and function impacting on the Sonic Hedgehog signaling, with critical implications for cerebellar development and tumorigenesis. We currently aim to dissect how NBS1 regulates cytoskeletal organization and primary cilia dynamics and how this eventually impacts on medulloblastoma development.

Additionally, we are interested in deciphering whether the more aggressive behavior of specific subsets of SHH-type medulloblastoma might be dependent on dysfunctions of the primary cilia.

3. Dissecting the epigenetic landscape in neuroblastoma and colorectal cancer to identify druggable epigenetic alterations

Drug discovery targeting epigenetic regulators is a dynamic area of research, however the epigenetic modifiers with a critical role in promoting neuroblastoma and colorectal cancer tumorigenesis are largely unknown. Our study is aimed to identify druggable epigenetic alterations with particular focus on protein lysine methyltransferases (PKMTs) such as SETD8 and its histone/non-histone targets.

SETD8 is a PKMT that beyond its histone target H4, also mono-methylates p53 on lysine 382 (p53K382me1), thus leading to the inhibition of p53 pro-apoptotic and growth arresting functions. We aim to investigate the post-translational mechanisms of p53 regulation and its functional inactivation in colorectal cancer stem cells and tumor-associated macrophages during tumor initiation and progression.