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Greg Ngo

Dr Greg Ngo

Research Fellow

School of Medicine

Email
NgoG@cardiff.ac.uk
Campuses
Cancer Genetics Building, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
Users
Available for postgraduate supervision

Overview

DNA-RNA Hybrids & Genome Stability Lab

My current research focuses on understanding the formation of R-loops, enigmatic structures containing DNA-RNA hybrids, at DNA double strand breaks, and how this process affects genome stability and the risk of developing neurodevelopmental disorders such as intellectual disability, autism spectrum disorder (ASD) and attention deficit hyperactive disorder (ADHD).

Publication

2022

2021

2018

2017

2015

2014

2011

2010

2009

2008

2007

2004

2003

Articles

Research

I have a long-standing interest in DNA repair and its contribution to genome stability, focussing 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 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 are associated with inherited risk for developing neurodevelopmental disorders.

My research goals are to establish the molecular mechanism 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, bioinformatic and neurosciences. Key techniques we use include CRISPR gene editing,  quantitative amplification of single-stranded DNA (QAOS), 2-dimensional DNA gel, single molecule PCR amplicon analysis, next generation sequencing (NGS), long-read nanopore sequencing, DSB mapping (INDUCE-seq) and induced pluripotent stem cell technologies.

Biography

I became interested in genome stability when I was involved, as an undergraduate project student, in studying DNA repair mutants in E.coli (laboratory of Prof. Robert Lloyd, University of Nottingham). As a research assistant for Dr. Thorsten Allers (University of Nottingham), I then worked on the archaeon H.volcanii, where I helped to develop genetic tools to study homologous recombination (HR).

During my D.Phil. study with Prof. Ian Hickson (University of Oxford), I characterised genes that genetically interact with the Bloom helicase (Sgs1) in budding yeast, and successfully identified Esc2 as a novel factor required for HR at stalled replication forks.

Following my D.Phil. study, I joined the laboratory of Prof. David Lydall (Newcastle University) to investigate the mechanism of DNA repair at uncapped telomeres in budding yeast. My work provided novel insights into the important role of DNA resection in cellular senescence and revealed that this process is finely tuned by various DNA damage checkpoint proteins.

I then joined the laboratory of Prof. Duncan Baird (Cardiff University) to work on telomeric DNA repair in human cells. I showed that PARP inhibitors selectively eliminate cells during telomere crisis, thus preventing cell immortalisation. This proof-of-concept study shows that ‘telomeric lethality’ could be exploited to prevent cancer progression. Recently, I successfully detected R-loops directly at DSBs for the first time and showed that these structures are generated 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

Angelos Damo

Research student