Dr Gabriella Ficz

Dr Gabriella Ficz

BSc, PhD
Centre: Haemato-Oncology
Lecturer - Early Career Researcher
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My group is interested in how normal cells turn into cancer cells and what role aberrant epigenetic alterations and reprogramming events play in this process

Research Details

Epigenetic mechanisms (including DNA methylation, histone modifications and nucleosome positioning) allow genetically identical cells to functionally diversify and, whilst reversible, they are specific for each cell type and have essential roles in reinforcing cellular identity. Epigenetic analysis of human cancer DNA has revealed widespread aberrations where global hypomethylation of repetitive sequences is accompanied by selective promoter hypermethylation, but how these apparently opposing mechanisms are brought about is unknown. The latest concepts involving the existence of cancer stem cells indicate that the earliest events generating aberrant mutations might occur even in the adult stem cell niche from which clonal evolution occurs.

The challenge in the cancer epigenetics field is to identify the driver epigenetic changes in the genome that enable early steps in cellular transformation and to understand the downstream molecular events and signalling factors driving these processes. Having a detailed mechanistic insight of the signalling events causing aberrant targeting of the maintenance methylation machinery will lay the foundation for a novel design rationale for epigenetic therapies.

Relevance to cancer:

Understanding how the epigenome can contribute to cellular transformation is fundamental to cancer research. The cancer epigenetics literature offers abundant correlative data on epigenetic changes associated with various forms of cancer but very few studies focus on the early phases of transformation, and specifically on the mechanisms whereby changes in the epigenome can pave the way to cellular transformation. At present there is no in vitro model available to study how targeted epigenetic changes can lead to transformation. My ambition is therefore to understand the roles epigenetic marks play particularly on the DNA in early cellular transformation.

Specific aims of the research:

    1. Mechanistic link between signaling networks and DNA methyltransferases (DNMTs)
    2. Application of epigenetic editing technologies to investigate phenotypic consequences of epimutations in primary human cells
    3. Gain insight into the mechanism of aberrant methylation accumulation seen in cancer cells

Also in this group:

  • Ms Lily Hoa (Research Assistant)

Profile

I started my research career at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany as a masters student at the first International MSc/PhD Research School in Molecular Biology. Here I had the opportunity to work with exceptional people in various research areas and this inspired me in my work for the years to come.

I came across Epigenetics early on and was fascinated by the paradigms and the questions at that time, so in 2002 I decided to do my PhD with Donna Arndt-Jovin working on the Polycomb-group of genes (PcG), which control body patterning in the fruit fly model system. I found that the PcG proteins are extremely dynamic on the genes they control, presumably having the ability to quickly respond to environmental signals in development.

Later on, for my postdoctoral research, I joined the group of Prof. Wolf Reik at the Babraham Institute, University of Cambridge, in 2005 where I worked on Epigenetic reprogramming in the mammalian system. We were seeking to find the elusive mechanism capable of erasing the epigenetic memory in cells. This memory, in the form of a chemical methyl group on the 5’ position of cytosines in the DNA, is essential for normal mammalian development and for maintaining identity of adult cells. Such reprogramming happens at fertilization and in germ cells in order to re-establish totipotency in early embryogenesis. After the discovery of the TET (ten-eleven translocation) protein activity, which oxidises 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), we mapped for the first time the genomic positions where 5hmC is generated in mouse embryonic stem cells and found that indeed this mechanism is in part responsible for removing the repressive 5mC signal in DNA.

In 2013 my research indicated that epigenetic reprogramming is mediated as well by signalling networks, which control the genes involved in maintaining the methylation patterns in cells. This made me understand the relevance of such mechanisms in health and disease therefore I decided to investigate them in adult stem cells which regenerate our body and have direct impact on ageing and cancer. I have been appointed Lecturer and Early Career Researcher in September 2013 and will undertake this research at the Barts Cancer Institute, Centre for Haemato-Oncology.

Funding

  • 2015 - Medical Research Council, New Investigator Award: “Elucidating the molecular and epigenetic basis of cancer initiation”, £860,000

Key Publications

Gabriella Ficz, Timothy A. Hore, Fátima Santos, Heather J. Lee, Wendy Dean, Julia Arand, Felix Krueger, David Oxley, Yu-Lee Paul, Jörn Walter, Simon J. Cook, Simon Andrews, Miguel R. Branco, and Wolf Reik. FGF Signaling Inhibition in ESCs Drives Rapid Genome-wide Demethylation to the Epigenetic Ground State of Pluripotency. Cell Stem Cell, 2013 PMID: 23850245

Gabriella Ficz and Wolf Reik. Reprogramming by cell fusion: boosted by Tets. Mol Cell, 2013. PMID: 23541036

Michael J. Booth, Miguel R. Branco, Gabriella Ficz, David Oxley, Felix Krueger, Wolf Reik, Shankar Balasubramanian. Quantitative sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single nucleotide resolution in ES cells. Science, 2102. PMID: 22539555

Gabriella Ficz*, Miguel R. Branco*, Stefanie Seisenberger, Fátima Santos, Felix Krueger, Timothy A. Hore, C. Joana Marques, Simon Andrews & Wolf Reik. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature, 2011. PMID: 21460836


Further Publications

For additional publications, please click here


My group is interested in how normal cells turn into cancer cells and what role aberrant epigenetic alterations and reprogramming events play in this process

External Activities

  • Mentoring young researchers to excellence
    Invited to speak at the ICR/Wellcome Trust Sanger Institute “Pathway to Independence; Developing future scientific leaders” programme (March 1st 2016, The Royal Institution of Great Britain)
  • Contribute regularly to the Max Planck Institute/Göttingen University MSc/PhD Programme Alumni magazine, the latest article detailing personal experiences in my transition to academic independence, Title: "Living the dream I never dared to have" (Page 18)
  • Public engagement
    Presentation at the Pint of Science Festival, London 2014 “Will a bad memory kill you: Epigenetics at a glance”
  • Invited speaker at TEDx Bucharest on “Epigenetics and Stem cells”, 16th October 2009

News

See other researchers working on:

Blood cancers Cancer and Ageing Genetics Stem Cells
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