World Epigenetics Summit 2012

Hanson Wade

Highlights

The 3rd World Epigenetics Summit took place on July 24th, 2012 in the scientific hub of Boston, Mass. We recruited Arun Kannanganat from the University of Maryland Baltimore County to take a few days out of his summer to help fill us in on everything that happened. Dive into his report below to get more meeting details:

World Epigenetics Summit Overview

The importance of “Epigenetics” / “Environment” could not have been better experienced in any other city. While interacting with leaders from industry and academia, it was an enriching experience to take a peek into the new exhibitions at the Broad institute, apart from the multitude of things that Boston has to offer. This conference stands apart from others in a sense that it was predominantly attended by Chief Scientific Officers (CSO) and Vice Presidents (VP) from the Industry. It indeed was a delight to see the enthusiasm and infectious vibe among them to tackle the most important challenges in translational research.

Apart from the presence of leaders representing companies like PerkinElmer, Pfizer, Epizyme, Celgene, Syndax Pharmaceuticals, Agilent Technologies, Astex Pharmaceuticals, Repligen, 4SC etc, the meeting was also graced by presentations by stalwarts in epigenetics from academia like Dr. Stephan Baylin (Johns Hopkins university). The mixture of discussions on clinical trial data, propelled by emerging concepts / results from academia is what made this event unique. The idea of learning in a “melting pot” environment was truly realized at this conference.

The speed networking session on day one was an ideal event to swap business cards and also paved the path for future conversations. Everyone had about 40 seconds to talk to a set of 5 people around a table after which 3 from each table would keep shifting tables while the other three stayed. The organizers (Hansonwade) did a great job of ensuring that everyone interacted with at least 75% of the crowd in that session. The elegant pyramid shaped tea bags from Tea Forte for breaks and the drinks reception sponsored by PerkinElmer was yet another enticing opportunity to listen in on some great conversations. The poster presentations and “mastermind groups” (small groups of 6 – 8) to discuss key challenges and share experiences were also interesting avenues to interact and build bridges. Though most of the talks were truly engaging below are some of select ideas / people from the event.

 

The Evolving Story of Epigenetic Collaboration

Mark Bunnage, Pfizer

Dr. Bunnage highlighted the importance of collaboration and exchange of ideas in fostering innovation by detailing the partnership of Pfizer with Structural genomics consortium (SGC – http://www.thesgc.org/). The goal of this significant public-private collaboration which also has other industry leaders like Novartis, Eli Lilly, GlaxoSmithKline etc, is to explore new small molecule probes to target various epigenetic targets and sharing this information in the public domain to drive research in key areas.

A very strong argument for the importance of Bromodomains was made by Jim Audia (Constellation Pharmaceuticals) in an earlier talk and was further stressed upon by Mark. The relevance of protein methyl transferases (PMT’s) was emphasized by the discussion of a potent small molecule inhibitor for SETD7. The talk was a treat of beautiful images of enzyme-inhibitor interactions and some physiological assays (GFP tagged FRET assay) demonstrating the effects of BET (Bromodomain and extra-terminal domain) inhibition.

MYC Targeting Through Epigenetics

Jay Bradner, Dana-Farber Cancer Institute

Dr. Bradner put forth a very engaging argument emphasizing MYC’s role in cancer and how it could be targeted through epigenetic perturbations. As part of his opening remarks, he discussed a hypothesis put forth by Richard A. Young that the Bromodomain family acts as co-factors in facilitating MYC dependent transcriptional elongation. BET protein inhibition with JQ1 to down regulate myc-dependent target genes was elaborated upon. Also, since HDAC6 is implied in multiple myeloma (MM), development of a HDAC6 inhibitor was discussed in detail.

It was very interesting to hear the story of collaboration and support of investors / partners in propelling the drug into Phase 1 clinical trials. The myriad post-translational modifications of these enzymes were discussed as potential opportunities for drug discovery. Bradner called for industry to re-validate work done in academia on these small molecules in order to hasten the process of taking the drug from laboratory to bedside.

Histone Methyl Transferases

Robert Copeland, Epizyme

Dr. Copeland’s talk was concentrated on Histone methyl transferases (HMT’s). He discussed the role of DOT1L inhibitor in selectively targeting mixed lineage leukemia (MLL) rearranged B cells and the importance of only H3K79me1 and H3K79me2 being affected.  The strategy of developing inhibitors by studying the structure of S-Adenosyl methionine (SAM) which is a common factor in any HMT reaction and also screening known inhibitors at various concentrations for other protein methyl transferases was put forth as a model of “engineered serendipity”.

Revolution In Epigenetic Drug Discovery Strategies

Nessa Carey, Pfizer

Describing herself as a “scout” in the industry who facilitates collaboration, Nessa highlighted the challenges in epigenetics and affirmed that the industry has been making considerable progress in this new field. Along the lines of arguments made by Rajesh Chopra (Celgene) and Peter Ordentlich (Syndax Pharmaceuticals), she emphasized the importance of changing the way drug discovery is pursued currently. A point that was consistently argued upon was the idea of low dosage combinatorial approach of current chemotherapeutic drugs along with epigenetic drugs.

The need to revamp strategies for testing the toxic effects of a drug was pointed out, as many of the current processes are archaic and may be not suitable to study epigenetic drugs, even though current FDA requirements are along those lines. Also, the need to re-evaluate the use of xenograft models for studying efficacy of a drug and possibly to come out with better methods was touched upon. She urged that target identification is a space where companies can collaborate on and reduce duplication of efforts. With a slide on many famous orphans like Frodo Baggins (Lord of the Rings), she emphasized the importance of considering orphan diseases as a potential area for epigenetic drugs. Her amazing talk concluded with a brief description of the bustling enthusiasm in this field with the examples of the exponential growth of publications, conferences dedicated to epigenetics and even the appearance of an epigenetic mark in the recent Spiderman movie!

Re-programming the Epigenome

Stephen Baylin, Johns Hopkins University

Along with Alexander Meissner’s (Harvard Stem Cell Institute) intriguing talk on DNA methylation and its role in cell fate specification, Stephan Baylin’s talk was yet another treat for anyone curious about the cutting edge research in academia. An exemplary story of collaboration (Stand up to cancer – http://standup2cancer.org/), in which currently used drugs (5-Azacitidine) along with epigenetic drugs (Entinostat) in cancer therapy was discussed in detail, including the clinical trial data from this combinatorial approach. During one of the “Tea Forte” breaks, he commented on my inquiry about higher order chromatin organization by saying that the area of research was “critical, critical and critical”.  To listen in on his enthusiasm about filtering out and analyzing data in a “post-doc” mode with those who surrounded him soon after his talk was indeed an inspiring moment. A very important idea of reprogramming the epigenome to make cancer cells sensitive to chemotherapy was also put forth.

Sasha Tarakhovsky (Rockefeller University) had also elegantly argued along similar lines in his talk about the importance of studying the “analogue” (secondary response genes) signal and modulating it through epigenetic perturbations. The example of a BET inhibitor being capable of affecting only 5 genes was really intriguing. The importance of the development of “histone mimics” was conveyed by discussing about NS1 (A natural histone mimic found in Influenza).

Interesting New Epigenetic Techniques

RapidFire – Agilent Technologies

William Lamarr

The RapidFire High-throughput mass spectrometry system with the power of reading a single 384 well plate in under 40 minutes was discussed as a label-free method for extracting high quality drug discovery data, studying histone modifications and for screening biochemical assays.

Combinatorial Domain Hunting (CDH) in Drug Discovery – Domainex Ltd.      

Philip Fallon

Philip explained the combinatorial domain hunting (CDH) approach of Domainex Ltd. to accelerate drug discovery and talked about the application of bio-layer interferometry in studying protein-protein interactions in this area.

On the Horizon

Daniel Vitt (4SC) in his talk on HDAC inhibitors, while describing two key drugs in their respective clinical trials, called for collaboration to propel one of those drugs into the second clinical trial stage. Robert Copeland (Epizyme) assured the audience that there will be much more interesting results from their ongoing clinical trials to be discussed at the 4th World Epigenetics Summit to be held in London (4th – 6th December,2012). Also the next EpiCongress will be held in Boston (23rd – 25th July, 2013), which having been inspired by this infectious vibe at Boston, I am personally looking forward to attend.

**EpiGenie thanks Arun Kannanganat, who is pursuing his master’s thesis under the guidance of Dr. Farabaugh (Biology Department) at University of Maryland Baltimore County (UMBC) for providing this conference coverage.