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Lee Wong Lab research

CollaborationsStudent research projects | Publications

About Associate Professor Lee Wong

Lee did her PhD at Monash University. Her post-doctoral work at Murdoch Childrens Research Institute marked the beginning of her chromosome biology studies. In 2012, she established her own lab, the Epigenetics and Chromatin (EpiC) Research Laboratory, in the Department of Biochemistry and Molecular Biology at Monash.


Our research

Current projects

1.  Investigate chromatin defects associated with Alternative Lengthening of Telomeres, a mechanism used for telomere elongation in cancers

2.  Define the roles of genome regulators - ATRX and histone H3.3 in tumorigenesis

Visit A/Prof Wong’s Monash research profile to see a full listing of current projects.

Research activities

Recent studies have identified the frequent mutations of histone variant H3.3 and its chaperone ATRX in human cancers including childhood brain cancers. The current aim of our team is to define the normal function of H3.3 and ATRX in controlling transcription silencing at the telomeres and at other repetitive DNA sequences in the global genome. We also investigate genome-wide epigenetic defects associated with H3.3 and ATRX mutations in cancers.

Project 1
Investigate chromatin defects associated with Alternative Lengthening of Telomeres, a mechanism used for telomere elongation in cancers

Telomeres are tandem arrays of DNA repeat found at the chromosome ends and are protected by a multi-protein “Shelterin complex”. The ability to maintain telomere length is crucial for continual cellular proliferation. Human cancers achieve the capacity for unlimited cellular proliferation by either aberrant reactivation of telomerase or activation of a DNA recombination-based mechanism known as Alternative Lengthening of Telomeres (ALT). ALT activation is common in tumours of the bone, soft tissue, and nervous system. ALT cancers have poor prognosis and therapeutic outlooks, and this is in part due to our lack of understanding of ALT process, particularly, the factors that suppress ALT activation and initial events that drive ALT. Recent DNA sequencing studies have identified the links of ATRX (Alpha Thalassemia Mental Retardation X-linked) mutations with the activation of the ALT pathway in cancers. Our aim is to determine the roles of ATRX and histone H3.3 in directing the formation of a transcriptionally silenced heterochromatin structure at the telomeres, and how ALT is initiated when the function of ATRX or H3.3 is lost in cells.

Split images of staining of repressive histone mark-trimethylated H4K20 at the centromeres and telomeres in mouse embryonic stem cells

Project 2
Define the roles of genome regulators - ATRX and histone H3.3 in tumorigenesis

Paediatric glioblastoma multiforme (pGBM) is a devastating disease with a 2-year median survival rate. Despite advances in treatments of other cancers, the outcomes for pGBM have remained unchanged for the past 40 years. The lack of effective treatments can be attributed to a poor understanding of the fundamental molecular changes, which underlie these tumours. Recent studies have identified frequent mutations in chromatin factor ATRX (α-thalassemia/mental retardation syndrome-X-linked) and histone H3.3 in pGBM, implicating them as major mediators in the pathogenesis of pGBM. Our aim is to characterise chromatin and transcriptional abnormalities associated with ATRX and H3.3 mutations and to determine how these abnormalities work in concert to promote gliomagenesis. This knowledge will be instrumental for the development of effective and targeted therapies for these cancers, which are refractory to standard chemotherapeutic interventions.

Techniques/expertise

Molecular and cell biology, chromatin analyses, CRISPR/Cas9 DNA editing.

Disease models

Mouse and human cell models.


Collaborations

We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

  • Prof Ross Hannan (John Curtin School of Medical Research)
  • Prof Philippe Collas (University of Oslo)
  • A/Prof Jeffrey Mann (Monash University)
  • Dr Elaine Sanij (Peter MacCallum Cancer Institute)

Student Research Projects

The Lee Wong Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short-term research opportunities available. You are encouraged to contact A/Prof Lee Wong regarding potential projects that align with the presented research themes.