Dr Greg Ngo

Publication

• Date
• Type

Research

I have a long-standing interest in DNA repair and its contribution to genome stability, focusing on the repair of DNA double-strand breaks (DSBs) and dysfunctional telomeres. Over the past 20 years, I have developed unique expertise in the analysis of DNA repair intermediates/products and have contributed to the understanding of various DNA repair mechanisms in humans and model organisms (budding yeast, archaea, and bacteria).

More recently, I have become interested in the role of DNA-RNA hybrids in DNA repair, following my discovery that R loops accumulate at DSBs. Furthermore, I found that two genes, UPF1 and UPF3B, stimulate the formation of these enigmatic structures in human cells. Intriguingly, dysfunction in UPF1 and UPF3B is associated with an inherited risk for developing neurodevelopmental disorders.

My research goals are to establish the molecular mechanisms that promote R-loop formation at DSBs and understand how these structures affect genome stability and the development of neurodevelopmental disorders. To do this, we use a multidisciplinary approach that combines genetics, biochemistry, bioinformatics, and neuroscience. Key techniques we employ include CRISPR gene editing, quantitative amplification of single-stranded DNA (QAOS), two-dimensional DNA gel electrophoresis, single-molecule PCR amplicon analysis, next-generation sequencing (NGS), long-read nanopore sequencing, DSB mapping (INDUCE-seq), and induced pluripotent stem cell technologies.

Lab members

Dr Siamak Kamranvar

Dr Ashley Parkes

Biography

My interest in genome stability ignited during my undergraduate project, where I was studying DNA repair mutants in E. coli under the guidance of Prof. Robert Lloyd at the University of Nottingham. As a research assistant for Dr. Thorsten Allers, also at the University of Nottingham, I transitioned to working on the archaeon H. volcanii, contributing to the development of genetic tools to investigate homologous recombination (HR).

Subsequently, during my D.Phil. studies under the mentorship of Prof. Ian Hickson at the University of Oxford, I characterized genes that genetically interact with the Bloom helicase (Sgs1) in budding yeast. This research led to the identification of Esc2 as a novel factor essential for HR at stalled replication forks.

Following completion of my D.Phil., I joined the laboratory of Prof. David Lydall at Newcastle University to explore the mechanism of DNA repair at uncapped telomeres in budding yeast. My work shed light on the crucial role of DNA resection in cellular senescence, unveiling its intricate regulation by various DNA damage checkpoint proteins.

My research journey continued at Cardiff University, where I joined the laboratory of Prof. Duncan Baird to investigate telomeric DNA repair in human cells. Through my studies, I demonstrated that PARP inhibitors selectively eliminate cells during telomere crisis, presenting a promising avenue for preventing cell immortalization and impeding cancer progression. Recently, I made a ground breaking discovery by directly detecting R-loops at DNA double-strand breaks (DSBs) for the first time, revealing their generation by UPF1 to stimulate DNA repair.

In 2023, I was awarded a Wellcome Trust Career Development Award to investigate the roles of R-loops and mutations in the pathogenesis of neurodevelopmental disorders.

Supervisions

I am interested in supervising PhD students in the areas of:

• Genome stability
• DNA repair
• Neurodevelopmental disorders

Current supervision

Angelos Damo