Epigenetic dysregulation is now a hallmark of several complex pathologies, including cancer, metabolic disorders, cardiovascular and neurological diseases. Disease-specific epigenetic signatures such as DNA methylation, hydroxymethylation, and non-coding RNAs are now being utilized clinically for prognostics and diagnostics, while an expanding collection of genetically aberrant, abnormally expressed or chromatin-interacting epigenetic enzymes are positioned as promising targets for therapeutic intervention. The Clinical Epigenetics conference is designed to explore the complete landscape of clinical epigenetics - from diagnostic to therapeutic advances - highlighting the unprecedented impact of epigenetics on precision treatment and medicine.
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Monday, February 10
10:30 am Conference Program Registration
KEYNOTE SESSION: CANCER (EPI)GENOMICS
11:50 Chairperson’s Opening Remarks
Babak Alizadeh, Ph.D., Co-founder & COO, PrognosDx Health, Inc.
12:00 pm The Cancer Epigenome
Peter A. Jones, Ph.D., D.Sc., Director, USC Norris Comprehensive Cancer Center; Distinguished Professor, Urology, Biochemistry & Molecular Biology, Keck School of Medicine, University of Southern California
Recent genome sequencing projects have revealed a surprising number of unanticipated mutations in genes which modify the epigenome. These studies have revealed a much closer interaction between the genetic and epigenetic basis of human cancer. We have begun to explore the potential effects of these mutations on the epigenome, paying particular attention to the existence and roles of chromatin accessibility in carcinogenesis. There is also excitement at the potential to use drugs to target these changes and I will discuss the effects of DNA methylation inhibitors.
12:30 Crosstalk between 5-Methylcytosine, 5-Hydroxymethylcytosine and Histone Modifications in Cancer
Gerd Pfeifer, Ph.D., Lester M. and Irene C. Finkelstein Endowed Chair, Biology & Professor, Epigenetics and Genetics of Cancer, Cancer Biology, City of Hope
Although changes of the epigenome, such as perturbation of DNA methylation patterns, are common events in human cancer, their contribution to the initiation and progression of malignant tumors has remained unclear. We have analyzed histone and DNA cytosine modifications in human cancer and normal tissue. The relationship between chromatin marks and cytosine modifications will be discussed. We propose a model in which specific epigenetic changes are shown to be important for the selection of tumor-driving events and thus may play a major role in cancer progression.
1:00 Session Break
1:15 Luncheon Presentation I: Accelerating Large Scale Genomics and Translational Research Using an Integrated High Performance Computing Solution
Kathy Tzeng, Ph.D., Team Lead, Life Sciences Solution Enablement, IBM
Scott Markel, Ph.D., Principal Bioinformatics Architect, Accelrys
Advancements in life science research and translational medicine drive the need for new technologies and computing approaches. These approaches pose challenges for IT leaders, researchers and developers to manage, share and store higher data volumes with greater efficiency at lower cost. Life sciences industry experts will discuss compute- and data-intensive challenges, the latest IBM genomic medicine solutions and real-world strategies adopted by leading genomic research institutes for large-scale data projects.
1:45 Luncheon Presentation II: Beyond Known microRNAs: Exploring the Rest of the Small RNA Transcriptome
Todd M. Lowe, Ph.D., CSO, Maverix Biomics, Inc.
Within the human transcriptome, microRNAs have proven to be the most dynamic, functionally important class of small non-coding RNAs, influencing the regulation of the majority of protein coding genes. However, largely unexplored small RNA transcriptome data sets, both public (ENCODE, TCGA, SRA) and private, have revealed a very wide range of novel small RNA transcripts with potential to be new biomarkers or uncharacterized regulators. To enable hands-on exploration of RNA-seq data sets by a much larger community of biologists, we have developed the Maverix Analytic Platform, integrating tools and data at the command of any researcher. We show examples of these overlooked classes of small RNAs to illustrate the untapped opportunities for discovery.
2:15 Session Break
KEYNOTE SESSION: BIOTECHS FUELING EPIGENETIC DRUG DEVELOPMENT
2:30 Chairperson’s Remarks
Jonathan D. Licht, M.D., Johanna Dobe Professor & Chief, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University
2:35 Targeting Wnt and Hh Pathway with 4SC-202, a New Epigenetic Therapy in Clinical Phase I
Daniel Vitt, Ph.D., CSO, 4SC AG
4SC-202 is a new epigenetic therapy targeting cancer stem cells and is currently evaluated in a clinical phase I trial (TOPAS). The molecule is an oral drug targeting LSD1 and HDAC isoforms 1,2 and 3. Interestingly, 4SC-202 is a potent modulator of the Wnt and Hedgehog signaling pathway, which was demonstrated in pre-clinical and clinical biomarker work. Primary endpoints comprise safety, tolerability and pharmacokinetics. As secondary objective several PD/biomarker readouts are evaluated including ex vivo assays to determine the extent of enzyme inhibition, protein acetylation and gene regulation in blood cells, and the modulation of cytokine levels and free circulating miRNA in patients’ plasma. So far, first very promising hints of anti-cancer efficacy could be determined by response of two patients and long term stabilization of numerous heavily pre-treated patients.
3:05 Small Molecule Inhibition of BET Protein Bromodomains: Mechanisms of Action and Potential Therapeutic Applications
Michael R. Cooper, M.D., CMO, Constellation Pharmaceuticals
Constellation and others are now developing small molecule inhibitors of BET protein bromodomains that have pharmaceutical properties suitable for clinical application. Given that the anti-tumor activity of BET inhibitors may arise from the suppression of a number of different cancer-relevant genes, the challenge will be to identify the most important determinants of anti-tumor activity in different malignancies. The presentation will review mechanistic studies of BET inhibitors and discuss potential molecularly defined disease subsets for clinical evaluation.
3:35 Early Clinical Development of OTX015, a Potent BET Bromodomain Inhibitor
Esteban Cvitkovic, M.D., Co-Founder and CSO, OncoEthix
I will present key information on the molecule and clinical formulations of OTX015, providing results from randomized, placebo-controlled trials in healthy volunteers. Also, preliminary results from ongoing dose-range finding studies in patients with relapsed/refractory hematologic malignancies will be discussed.
4:05 Chromatin Remodeling - A Novel Strategy to Control Harmful Alcohol Drinking
Dorit Ron, Ph.D., Professor, Neurology and Endowed Chair, Cell Biology, University of California, San Francisco
4:35 Refreshment Break and Transition to Plenary Keynote
6:15 Grand Opening Reception in the Exhibit Hall with Poster Viewing
7:45 Close of Day
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