Invetech Scientist, Rebecca Newman, has a background in biotechnology and epigenetics (DNA methylation assay development). Her passion for the latest in epigenetics research is a constant, in addition to what its impact may be on the future of diagnostic technology.

Given this passion, Rebecca was drawn to a recent event in Melbourne, Convergence Science Network’s Spotlight on Couples in Biomedical Science, where husband and wife Sarah-Jane and Mark Dawson discussed their latest work in liquid biopsies and epigenetics research.

Below are a few of Rebecca’s personal highlights from the talk. You can also watch the full presentation on YouTube.

Liquid Biopsies: Monitoring the cancer genome in blood

Sarah-Jane is both a medical oncologist and clinician scientist. She has a focus in breast cancer treatment and management, and from a research perspective, developing improved molecular biomarkers for early detection and disease monitoring of cancer. For Sarah-Jane, this specifically means exploring and developing non-invasive blood-based biomarkers (liquid biopsies) for clinical applications in breast cancer.

The research she presented showed that the information obtained through sampling blood for ctDNA (circulating tumor DNA) is highly concordant with the information from tissue and bone marrow biopsies. Liquid biopsy as a clinical tool is very powerful as it is non-invasive and you can take regular blood samples to aid early detection, monitor disease progress, and perform risk stratification in cancer management.

Sarah-Jane ended her presentation with data showing high concordance between liquid biopsies and bone marrow biopsies which was a nice segue into Professor Mark Dawson’s presentation on his research into epigenetic regulation in normal and malignant hematopoiesis (the process that leads to the formation of all blood cells).

Epigenetics: Providing a table of contents for our DNA

To facilitate the understanding of his research, Mark provided an explanation of Epigenetics to the audience (a mix of scientists and non-scientists) in what I thought was an elegant analogy to introduce such a complex concept. The example was of the caterpillar that encloses itself in a cocoon and through metamorphosis emerges as a butterfly. The caterpillar and butterfly are genetically identical, but drastically different looking. Epigenetics can be explained as the mechanisms that dictate different genes being expressed at different times in the life of the caterpillar.

So how does epigenetics factor into regulation in normal and malignant hematopoiesis? It has been known for a while that cell fate is not a one-way path and Mark recounted a moment many years ago at a pub in the UK where he was sharing a drink with Sir John B. Gurdon (who jointly was awarded The Nobel Prize in Physiology or Medicine 2012, together with Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent).

Mark asked Sir John why he did the nuclear transfer experiment that led to his Nobel award many years later. Sir John responded that he wanted to challenge the dogma that cells are irreversibly committed to their fate. He was referring to the experiment where Gurdon removed the immature cell nucleus in an egg cell of a frog, and took the nucleus from a mature frog intestinal cell, and placed it into the nucleus-free egg. The experiment ultimately resulted in living tadpoles!

The results of these experiments showed that DNA of a mature cell still have all the information needed to develop all cells in the frog, and that cell fate is reversible. This early discovery of cell fate is highly relevant for blood cancers, especially Acute Myeloid Leukemia (AML) which genetically is a simple disease (one translocation on a chromosome causes the disease).  However, identifying which patient will suffer a recurrence of the disease is dependent on assessing the epigenetic regulators.

Professor Mark’s research showed that AML could return to patients if they had a mutation on one of the Epigenetic protein regulators. This discovery led to Mark being able to target the epigenome with drugs that block defective proteins, and thus investigate therapeutic resistance in AML. However, three years ago they discovered that BET inhibitor (anti-cancer) drug resistance develops in the stem cells. This evolution from being sensitive to resistance showed no evidence of any mutation, instead, different pathways were triggered. To visualize these different protein pathways and how drugs blocked them, Mark cleverly employed a street map to show how the normal fastest routes are blocked by regular drugs and how epigenetic techniques “understand” the cells and predict the next route and subsequently block proteins there.

Final thoughts

My lasting impression of the presentations was not only how elegantly both Sarah-Jane and Mark made these very complex phenomena easy to understand, but how important these tools will be in the future of clinical diagnostics to improve outcomes for persons suffering from cancer and other illnesses. I recommend people find a moment and watch the video of the event.