Dr Roberto Bellelli

MD, PhD
Lecturer
Group Leader
Research Focus

My lab aims to understand the basic mechanisms controlling DNA replication in mammalian cells and how disruption of this process leads to genomic instability and cancer.

Key Publications

POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication. Mol Cell (2018) 72(1):112-126.e5. PMID: 30217558

Polε Instability Drives Replication Stress, Abnormal Development, and Tumorigenesis. Mol Cell (2018) 70(4):707-721.e7. PMID: 29754823

NCOA4 Deficiency Impairs Systemic Iron Homeostasis. Cell Rep (2016) 14(3):411-421. PMID: 26776506

NCOA4 transcriptional coactivator inhibits activation of DNA replication origins. Mol Cell (2014) 55(1):123-37. PMID: 24910095

Major Funding
  • 2020-2023 - Barts Charity, Roles of DNA Polymerase Epsilon in the maintenance of genetic and epigenetic stability.
Research

The maintenance of genome stability relies on the accurate and processive replication of genomic DNA and its dysregulation triggers genomic instability, a major hallmark of cancer.

Cancer cells are indeed characterised by a constitutive defective DNA replication, also known as replication stress, whose nature is still poorly characterised. Understanding how cancer cells perturb their chromosomal DNA replication, while increasing our knowledge of the causes and consequences of genomic instability in cancer, might also pave the way to the identification of synthetic vulnerabilities of cancer cells and novel therapeutic approaches.

My lab is interested in understanding the basic mechanisms that coordinate initiation and progression of DNA replication in mammalian cells, the links with the machinery that assembles nucleosomes at the replication fork and how dysfunctional DNA replication triggers genomic and epigenomic instability in cancer.

Thus, we combine classical cell biology and biochemistry, with state-of-the-art genomic and proteomic approaches to identify and characterise new factors involved in the maintenance of genome and epigenome stability at the replication forks and to search for novel vulnerabilities of cancer cells.

Major Funding
  • 2020-2023 - Barts Charity, Roles of DNA Polymerase Epsilon in the maintenance of genetic and epigenetic stability.
Biography

I studied medicine and surgery at the University of Naples, Federico II (Italy), where I graduated with honours in 2008 with a thesis on the molecular pathology of thyroid cancer.

After entering the Italian medical board, I joined the PhD program in Molecular Oncology and Endocrinology at the same faculty, and obtained my PhD in 2012. My work has been focused on the role of the NCOA4 gene, which is rearranged in human cancer, in the control of DNA replication and iron metabolism (Bellelli et al., Mol. Cell, 2014; Bellelli et al., Cell Reports, 2016).

In 2015, for my post-doctoral studies, I moved to the laboratory of Prof. Simon Boulton at the Francis Crick Institute in London, where I studied the mechanisms that control genome stability during DNA replication.

Using a combination of approaches, ranging from mouse genetics to biochemistry and cell biology, I discovered an essential double function for the POLE3-POLE4 components of DNA Polymerase Epsilon in the control of initiation of DNA replication and replication-coupled nucleosome assembly, with important implications for both human genetic disease and cancer (Bellelli et al., Mol Cell 2018a; Bellelli et al., Mol Cell 2018b).

In February 2020, I joined the Barts Cancer Institute as a Group Leader. My lab will study the mechanisms that control genome and epigenome stability at the replication fork and how they are dysregulated in cancer.

Upcoming Events
  1. MSc Cancer Programmes Live Q&A Event

    July 27 @ 1:00 pm - 4:30 pm
  2. The London Pancreas Workshop 2020

    September 11 @ 9:30 am - 4:30 pm
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