Interview with Jorg Tost and Francesco Crea – Senior Editors of Epigenomics
Expert Medicine presents an interview with Jorg Tost and Francesco Crea, Senior Editors of Epigenomics. Read on to learn more about some of the key areas of research within the field, our Senior Editors’ work, and why authors should submit their work to Epigenomics.
Please describe your specific area of research and how it relates to Epigenomics.
JT: In the Laboratory for Epigenetics & Environment, which I am heading at the National Centre for Research in Human Genomics (CEA-CNRGH) in Evry, France, we are developing and implementing technologies and bioinformatic workflows for the analysis of epigenetic modifications. These can be applied to disease-related projects in the field of immunological disorders (inflammatory, autoimmune and allergic diseases), but also cancer and neurodegenerative diseases. The overarching aim of many of the projects is to develop epigenetic biomarker signatures that could be applied for individualized patient management such as the response to a specific treatment. The second focus of the laboratory is the analysis of epigenetic modifications in function of environmental exposure, which can be toxicants such as tobacco smoke, but also positive influences such as a farm environment.
FC: My lab works on developing precision epigenetic therapies for drug-resistant cancers. For example, we are currently leading an international project funded by Prostate Cancer UK to optimize the use of Polycomb inhibitors, in combination with other therapies, to develop effective therapies for incurable prostate cancers. For this type of project, we use lots of “omics” tools like ATAC-Seq and CUT&RUN, to look at the effects of epigenetic inhibitors on the whole epigenome.
What does the field of epigenomics try to address, or what are the significant questions that the field aims to answer?
JT: Epigenomics investigates the control of gene activity as well as the establishment and maintenance of cell identity, and how this is changed by environmental exposures or disease. Epigenomics is currently at the centre of many biomedical questions, promising to at least partly explain the missing heritability of genetic studies and provide a link between the genome and our environment.
Key questions include how epigenetic profiles are established and maintained during development, which exposures or molecules will have a long-lasting influence on our epigenome, including in very early life, and whether they relate to disease and aging. Can epigenetic changes be passed down to subsequent generations? Can we reverse these changes or prevent them from happening by changing our lifestyle or by therapeutic methods? Can we improve the diagnosis of complex diseases through epigenetic biomarkers in a way that is sustainable within the public health care system? Is the modulation of gene activity through epigenetic editing or therapeutic approaches targeting parts of the epigenetic machinery a potential therapeutic option for diseases?
Epitranscriptomics, which covers the epigenetic modifications on RNA, has recently been shown to play an important role in the regulation of gene activity and cellular function, but has not been thoroughly investigated compared to the DNA or protein-based epigenetic modifications.
FC: Phenotypic plasticity is the process by which cells or whole organisms can generate different phenotypes from the same set of genes. The mechanisms enabling this phenomenon have been a mystery for a long time. Now we know that this phenomenon is mediated by epigenetics (DNA methylation, histone modifications, etc). Epigenomics aims to investigate the whole-genome causes of phenotypic plasticity. Since Phenotypic plasticity is the root of many physiological and pathological processes (e.g. cancer, immune disorders, neurodegeneration), epigenomics may hold the keys to unlock new therapies for prevalent and rare diseases.
How can research in epigenomics be applied to benefit broader industries?
JT: Epigenetic biomarkers are currently being investigated in many clinical trials, with some having been approved by regulatory agencies for more than a decade. Most applications focus on early-detection assays for specific cancers or multi-cancers or predicting the response to a therapy. While many focus on cancer therapy, there is an enormous potential for epigenetic biomarkers in many complex diseases, particularly those with a strong environmental component.
Beyond providing biomarkers, the epigenome is also a drug target. DNA methylation inhibitors in some forms of leukaemia and HDAC inhibitors for psychiatric diseases have been used in routine treatment for a long time, and different epigenetic enzymes (readers, writers, or erasers) have been targeted in various disease contexts. Recent advances in epigenetic editing are likely to enable the targeted modulation of gene expression of specific genes, and a number of clinical trials led by different companies are currently ongoing.
Finally, due to its close correlation with aging, the wellness and cosmetics industries have also discovered the epigenome as an interesting surrogate marker for biological aging using different epigenetic clocks with the aim of developing products and therapies to slow down and/or reverse the aging process.
FC: I think that a multidisciplinary approach is key to achieving translational impact (not only for industries, but for health benefits, which are arguably more important). Over the years, I have learnt to collaborate closely with both clinical and industrial experts. It is also important to focus on problems that are relevant to patients. I regularly give talks to prostate cancer support groups, and I receive immensely helpful feedback from patients and families.
Is there any cutting-edge research coming out of the field that has caught your attention recently?
JT: I am deeply impressed by the recent developments of both new technologies and computational biology for epigenetic analyses. One recent example is spatially resolved DNA methylation and transcriptome profiling, which gives a new dimension to epigenetic analyses, as well as the correlation to the direct functional outcomes.
In general, the field is moving to epigenetic multi-omic analyses, allowing for better assessment of the functional complementarity and redundancy of epigenetic modifications, but also confers the required sensitivity and specificity for biomarkers. These multi-level datasets also benefit from the advances in machine learning and artificial intelligence, which can be used to extract relevant information from the epigenetic data and facilitate clinical implementation of epigenetic biomarkers for personalized disease management and ultimately achieve measurable benefits for the mechanistic understanding, diagnostics, and therapy of disease.
FC: I am particularly excited about epigenetic liquid biopsies. These are tools that allow researchers to read the epigenome from small amounts of biological fluids (e.g., plasma). This approach was used successfully to profile the transcriptomic activity and therapeutic response of cancers. We also did a bit of work on this, which was published on Epigenomics.
What does the role of Senior Editor entail?
JT: As a Senior Editor, I discuss the overall strategy for the journal with the commissioning/handling editor. This includes adjusting the scope of the journal and helping the editorial team to identify emerging topics of research that the journal could be interested in and discussing outreach activities to promote and increase the visibility of the journal. I also play a key role in the peer review process, in making decisions on manuscripts where peer reviewers have opposing reports, or when issues regarding scientific integrity are raised.
FC: As a Senior Editor, I have more of an advisory role on the overall direction of the journal. I am proud of the work we did to increase the diversity of our Editorial board, including, for example, some early-career researchers. I am also involved in strategic decisions. For example, we decided to focus Epigenomics on biomedical research because we think this discipline is particularly promising for new therapies and new diagnostic tools. Sometimes it takes a long time to achieve impact as a Senior Editor, but when you do, you feel you have helped the community. For example, we are now working with the Commissioning Editor to develop a system that rewards academics who provide accurate peer review reports. Peer review is a valuable but unfortunately traditionally unrecognised role. I hope we will soon be able to announce some positive changes that will reward our Reviewers appropriately.
Why should other researchers within your field consider submitting their work to Epigenomics?
JT:When we launched Epigenomics back in 2010, it was the first journal focusing on the epigenome related to human health questions, filling a gap in the publishing landscape, as epigenetic articles used to be published in disease-specific journals. While other publishers have adopted this focus, I still consider Epigenomics as the main platform to communicate results on epigenetic research with relevance to human health, report on major challenges and critical advances. This is also supported by the usage statistics for Epigenomics, with 223,000 annual downloads and views.
The journal is supported by a professional team of handling editors and support functions, making the entire publication process as smooth as possible, and of course, indexed in all major databases, making your research easily findable. As a traditional journal, Epigenomics does not request any fees from authors, although an open access option is available for those who would prefer to make their research freely available.
FC: Epigenomics implements an accurate, fair, timely and rigorous peer review process. We have a pool of experienced Editorial board members who cover all the aspects of the discipline (from traditional epigenetics to non-coding RNAs). We have a special focus on bio-medical applications of epigenetic research, so if you work in this field you should consider our journal. Plus, publishing is free (there is an open access option), which helps at times when funding for research is being restricted in many ways.
We hope this interview has provided you with an overview of Epigenomic’s Senior Editor’s work and the aims and scope of the journal. Learn more about the Epigenomics journal and submit your work here.