Highlights
**Big thanks to Christina Taubert, our favorite grad student at the Francis Crick Institute in London for providing this conference coverage.
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The 2nd Annual Epigenetics Discovery Congress organized by Markets and Markets conferences was held at the London Heathrow Marriott Hotel, London/UK from 8th to 9th of September. It brought together key experts from academia and industry exchanging ideas and latest research in epigenetics and discussing potential sources for new drug targets as well as interesting challenges from the developmental to translational phase.
In general the congress highlighted some emerging themes in the drug discovery approach with respect to evolving targets, inhibitors, biomarkers and clinical success of epigenetics across various diseases. The talks focused around inhibitors (e.g. HDACi) and biomarkers (e.g. NDRG4) in various cancers as well as DNA methylation and its correlation and impact on different developmental and behavioral phenotypes.
Along side these, industry suppliers got the opportunity to present advancement in technologies and solutions and discuss bottlenecks of current methods. Following this scheme, posters from both, industry & academia, were displayed along side.
Epigenetic regulation of the tumour microenvironment (TME) – immune-oncology meets epigenetics
Dr. Svetlana Hamn | 4SC AG, Germany
Dr. Svetlana Hamn presented recent data regarding 4SC-202, a new clinical stage epigenetic regulator of the TME. 4SC-202 is a LSD1 and HDAC class 1 inhibitor, which proofed to be safe and well-tolerated in the clinical Phase I TOPAS trial. This compound leads to up-regulation of tumour associated antigens as well as MHC class II, therefore increasing immunogenicity. Additionally, 4SC-202 treatment increases the influx of CD4+ and CD8+ T cells to the tumour site. To reduce immunosuppression a combination of 4SC-202 with PD-1/PD-L1 block proofed to increase the CD8+/Treg cell ratio and lead to a huge increase in survival compared to single use of the compounds in in vivo studies (mouse). 4SC-202 is therefore a very promising epigenetic compound that strengthens the endogenous immune response to cancer.
Stability and flux of DNA methylation patterns
Dr. Reinhard Stöger | University of Nottingham, UK
Large genetic regulatory networks can acquire novel epigenetic states in response to environmental challenges. DNA methylation/de-methylation is a very dynamic process. To identify the preferred state of a cell, the Stöger’s lab developed a new metric that allows the comparison of epigenetic dynamics – Ratio of concordance preference (RCP). In his talk, Dr. Reinhard Stöger explained how RCP quantifies and compares epigenetic flexibility and stability across loci, cell types and developmental stages.
Findings in DNA methylation measured across the life-course in a large well-characterized human cohort
Dr. Matthew Suderman | University of Bristol, UK
The Suderman’s lab is using a big longitudinal study (ALSPAC, Avon Longitudinal Study of Parents and Children) to see if there are correlations with various different developmental phenotypes and CpG methylation. This cohort study of children born in the former county of Avon, England during 1991 and 1992, includes data from mother, father, child and siblings and now also children of the participants have begun to be studied. By analysing this cohort, the Suderman’s lab was able to show that developmental phenotypes are only related to birth weight and not gestation, as this phenotype resolves. Furthermore they demonstrated a link between maternal depression and CpG methylation in offspring, to only name 2 of the main findings Dr. Matthew Suderman presented in his talk. Surprisingly he found published mouse data to be very much reproducible in this human data set.
DNA methylation markers for management of cancer: pitfalls and perspectives
Prof. Dr. Manon van Engeland | Maastricht University Medical Centre, Netherlands
DNA methylations are very suitable as markers as they are frequent, stable, easy to measure and highly abundant in cancer. The lab of Prof. Dr. Manon van Engeland focuses on promoter methylation and discovered N-Myc downstream-regulated gene 4 (NDRG4) as a diagnostic factor for colorectal cancer. NDRG4 is a tumour suppressor gene that is hypermethylated at the promoter in colorectal cancer and nowadays is used to screen for colorectal cancer in the UK. Despite this success, and although the field has advanced enormously in the last years, from Prof. Dr. van Engeland’s point of view, the field has not delivered what it promised in terms of biomarkers for cancer diagnostics. She highlights the importance of the location of where one should look for the methylation and pointed out that validations of already discovered biomarkers in big cohorts are of great importance to bring these into the clinic.
All in all, the 2nd Annual Epigenetics Discovery Congress was a great platform to bring academia and industry together and enable fruitful collaborations and discussions during the breaks and poster sessions.