Ah, so many great meetings, so little time. Trying to attend all the epigenetics, stem cell, and synthetic biology oriented meetings nowadays would require Rolling Stones-like touring superpowers.
Lucky for us Aoife Ward from Cellzome, was able to step in and tackle this beauty. Here’s her take…
A stimulating three day meeting organised by the SGC (Structural Genomics Consortium) took place at the University of Oxford, UK. A unique blend of basic researchers, industry members and chemists gathered to focus on novel epigenetic targets in cancer and other diseases.
The focus on Day 1 was inflammation, where we heard a number of great talks linked to the immune system and disease. The role of the epigenetic reader class of bromodomain proteins as novel targets was the spotlight of the day as they appear to have important functions across a range of diseases. A lively poster session coincided with lunch, with a number of the posters being presented as short talks over the three days.
Day 2 was centered around epigenetics where we heard about a range of epigenetic target classes, including non-coding RNAs, and their impact on disease.
A medicinal chemistry workshop was organised for the final day. Here we heard about the design of target molecules for epigenetic proteins and some promising candidates.
It was a very exciting conference with a general theme of making research more open through sharing of chemical structures and molecules between both academia and industry to bring the science forward. Here are some highlights I chose:
Sensitivity and Resistance to Bromodomain Inhibition
Jay Bradner, Harvard Medical School
Jay’s opening plenary lecture was a personal highlight, as my research is built on his pioneering studies with the BET inhibitor JQ1. Since the synthesis of the selective small molecule, Jay has sent JQ1 to more than 500 labs around the world, paving the way for open source drug discovery. He nicely summarized some of the recent findings around JQ1.
He explained the tight regulation between BET proteins and MYC, the notoriously undruggable oncogene. Through targeting BETs, MYC dependant cancer can be blocked.
The Bradner group are devising a range of assays to better understand the BET proteins including an innovative method, Chem-seq, to map genomic binding sites of JQ1. Using such methods, they have shown that while BETs are primarily associated with gene promoters, a small fraction bind “super-enhancers” which may be even more important for disease pathogenesis. They are currently gearing towards animal studies with JQ1 as well as investigating resistance mechanisms to the small molecule.
Epigenetics: Progression of Pharmacological Tools for the Understanding and Treatment of Disease
Rab Prinjha, GlaxoSmithKline
Another very exciting update on bromodomain proteins, this time from an industry perspective. Rab talked about the role of BET proteins in inflammation and other diseases, highlighting their clinical potential. Aside from the BETs, he presented an overview of current bromodomain targets such as BRD9, which has also been linked to disease and inflammation.
Comprehensive Epigenome Maps of Innate Immune Cells: Identifying Therapeutic Targets
Henk Stunnenberg, Radboud University Nijmegen
Henk gave us an update from his work in the Blueprint Epigenome consortium, an effort to map the epigenome of immune cells. Using ChIP-seq and transcriptomics, they study monocyte to macrophage differentiation, looking closely on enhancers and promoters which are activated during the process. Interestingly, inflammatory and metabolic pathways functionally implicated in trained immunity were modulated, providing new insights into the innate immune system.
Towards a Chemical Probe Set Targeting the Human Bromodomain Family of Epigenetic Reader Domains
Stefan Knapp, University of Frankfurt
SGC member Stefan Knapp continued on the bromodomain theme. He and collaborators have used a screening approach to develop highly selective bromodomain inhibitors. He showed compelling data that long term treatment with bromodomain inhibitors affected cell differentiation, rather than proliferation.
From Hit to Phenotype: The SGC-Pfizer Chemical Probes
Dafydd Owen, Pfizer
Dafydd presented a couple of stories around novel bromodomain inhibitors, which are on the way to being published. They are dedicated to identifying phenotypes for new molecules. He again, highlighted the the availability of chemical probes to the scientific community, as a Pharma partner of SGC.
Discovery of Chemical Probes for Histone Methyltransferases
Jian Jin, Icahn School of Medicine, Mount Sinai
Jian gave us an overview of recent advancements on histone methyltransferases (HMTs) as epigenetic targets. His lab has taken a systematic approach by targeting the HMT substrate binding groove to inhibit a range of HMTs including SETD8 and PRMT3. The molecules are showing potent activity in both in vitro and in vivo models. He also described a potent and selective EZH1/2 inhibitor which he has shared with over 100 labs to date.
**EpiGenie would like to extend big thanks to Aoife Ward for hooking us up with this great summary.