Genomics Research 2012
The Genomics Research conference series may have a new name (it was formerly the Epigenetics World Congress), but it still has the same goal of bringing together representatives from every side of the epigenetic research sphere – from academia to corporate interests, and basic research to the clinic – to interact for a few days. This time, Brigham and Women’s Hospital and Harvard ‘s Rebecca Rancourt was on hand to capture what went down for the rest of us who couldn’t make it. Take a look at her report below:
Start Line – Genomics Research Overview
Just days after the Boston Marathon, the temperatures cooled for two days of talks taking place at the Genomics Research conference April 19-20, 2012. The meeting, organized by Select Biosciences, had sessions concentrating on RNAi and miRNA, Advances in qPCR, Genomic Biomarkers, Next-Gen Sequencing, and Epigenetics. The venue was the historic Boston Park Plaza, centrally located next to the beautiful Boston Public Gardens and just down the street from 100 year old Fenway Park (pronounced “Pahk”). Here is a brief overview of the topics and themes discussed in the Epigenetics sessions.
Future of Epigenetic Therapy
Epigenetic research in the cancer field has been normally considered in the way of biomarkers or predictors of disease, but many talks in the Processes in Disease section discussed treatment, and in particular the recently FDA-approved epigenetic therapy of 5-azacytidine (AZA) and 5-aza-2′-deoxycytidine. The recurring theme throughout the session focused on how using epigenetic modifying medicines in combination with conventional cancer therapy could be the ideal blend in the fight against cancer.
Malcolm Brock, Johns Hopkins Hospital
Dr. Brock illustrated the use of combination epigenetic therapy as a new way of treating solid tumors. Low dose treatments of DNA demethylation agents (such as AZA) followed by additional cancer therapy appear to be beneficial in studies with lung cancer patients showing a gradual decrease in tumor size.
Steven Smith, City of Hope
Dr. Smith continued the topic of 5-aza-2′-deoxycytidine, focusing on the possible roles of its primary degradation product of 2’deoxyriboguanylurea with intricate nucleic acid chemistry. He described how the degradation product could be causing the de-methylation activity, and that most effects may be due to DNA damage.
Peter Jones, University of Southern California
‘Lower is better’ in respect to 5’aza dose treatments for epigenetic therapy, and this was echoed in Dr. Jones’ keystone presentation on the cancer epigenome. After giving a great overview on the epigenetic components DNA methylation, histone modifications, and nucleosome positioning, he suggested that future research needs to step back from solely examining promoters and look into insulators, transcription factors, repetitive DNA, and enhancer elements.
Epigenetics of Enhancer Elements
Peter Scacheri, Case Western Reserve University
Dr Scacheri discussed the exciting ‘hot off the press’ work on Variant Enhancer Loci (VEL) in cancer, which was published in the April issue of Science. Little is known about the roles enhancer elements have in cancers and other diseases and even less about the epigenetic profiles of these elements. This research focused on colon cancer, using the ChipSeq technology to investigate histone marks in normal colonic crypt cells versus malignant ones. These analyses showed differences involving VELs leading to the question of whether VELs could be predictive of colon cancer. This work has enhanced interest for extending epigenetic research past promoters and identifying epigenetic profiles and roles that enhancer elements have in various diseases.
Letting Food Be the Best Epigenetic Medicine
Trygve Tollefsbol, University of Alabama at Birmingham
Dr. Tollefsbol continued the dialog on the Epigenetic diet, leaving us looking for green tea and broccoli at the coffee break. ‘What’ and importantly ‘how much’ we eat can aid in cancer prevention and may increase lifespan. Various studies have indicated that epigenetic-modifying compounds found in items such as cruciferous veggies, soybean products, and green tea can change DNA methylation and histone modification activity, and subsequently influencing gene expression. As portion control remains at the forefront of the war on obesity, the question of ‘how much?’ (caloric restriction) may also help with living longer. This was illustrated with in vitro experiments with human diploid cell line under glucose restriction, which extended the cells lifespan and reduced survival of precancerous cells. Further evidence of this has been observed in animal models, so perhaps controlled fasting can slow the aging process. At the core, the Epigenetic diet tells the long told story of eating more veggies (especially cruciferous ones), and limiting caloric intake such as reducing the amount of high sugar foods. Perhaps this new avenue may reach more of those interested in exercising their epigenomes.
Advances in Future Epigenetic Technology
Paul Hurd, Queen Mary University of London
The morning session of day two at the Next-Gen Sequencing meeting had epigenetic-themed talks starting with Dr. Hurd showing genome-wide mapping of chromatin modifications performed with ChipSeq. This analysis focused on 6 histone trimethylation marks and was performed in parallel with gene expression assays to investigate the modification landscape at active and inactive genes. This mapping experiment showed that some families of genes are epigenetically marked with particular combinations of histone marks.
Paul Soloway, Cornell University
Dr. Soloway presented the Single Chromatin Analysis at the Nanoscale technology (SCAN) as a top option for high-throughput single molecule analysis for epigenomic research. Some advantages to this technology over the ChIP assays are the rapid run time, ability to assess multiple epigenetic marks simultaneously, and the fact that this SCAN offers quantitative data.
This conference had a nice blend of research presentations covering various model systems including human, mouse, Arabodopsis, C. elgans, and flies….Oh my! The Select Biosciences conferences also incorporate the technological aspect by having a vendor presence. This conference offered frequent opportunities to network and have insightful scientific discussion. Deciphering how or when the genome interacts with the epigenome (and vice versa) could help us understand disease etiology and create personalized medicines. There are exciting new days ahead in this field, especially if we expand our attention to look beyond CpG islands and promoters.
**EpiGenie would like to offer many thanks to Rebecca C. Rancourt, Ph.D. who is a Research Fellow at the Harvard School of Public Health and the Obstetrics and Gynecology Epidemiology Center at Brigham and Women's Hospital, in Boston for her work providing this conference coverage.