2014 Archived Content

Cambridge Healthtech Institute’s Inaugural

Clinical Epigenetics

Interrogating Disease Epigenomes for Diagnostic, Prognostic & Therapeutic Utility

February 10-12, 2014 | Moscone North Convention Center | San Francisco, CA

 

Day 1 | Day 2 | Day 3 | Download Brochure 

Tuesday, February 11

7:00 am Registration and Morning Coffee


8:00 Plenary Keynote Session (Click Here For More Details) 


9:15 Refreshment Break in the Exhibit Hall with Poster Viewing 

 


NEXT-GENERATION EPIGENETIC TARGETS 

10:25 Chairperson’s Remarks

Dominique Verhelle, Ph.D., MBA, Director, Epigenetics, Tumor Cell Biology, Oncology Research Unit, Pfizer, Inc.

10:30 Disorders of Histone Methylation in Hematological Malignancy

Jonathan D. Licht, M.D., Johanna Dobe Professor & Chief, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University

I will discuss the recurrent mutations in epigenetic enemies affecting the pivotal change in hit one methylation between histone 3 lysine 4 ( H3K4me- activation) and H3K27me (repression). Among the proteins that will be discussed are EZH2, which is mutated in a substantial fraction of germinal center derived lymphomas; UTX, a histone demethylase for H3K27 that is deleted in multiple myeloma and other tumors; and WHSC1/MMSET, a gene over expressed in multiple myeloma as well as many solid tumors and mutated in a subset of acute lymphocytic leukemia.

11:00 Critical Roles of Histone Methyltransferases and Demethylases in Human Carcinogenesis

Ryuji Hamamoto, Ph.D., Associate Professor, Hematology & Oncology, The University of Chicago

It has become clear that methyl groups stand beside phosphate groups as major controlling elements in protein function. In this context, we have already identified a number of histone methyltransferases and demethylases, which are related to human cancer. According to our detailed functional analysis, these enzymes relevant to histone methylation are likely to play a crucial role in human carcinogenesis. Development of anti-cancer drugs targeting histone methyltransferases and demethylases appears to be an important approach in cancer treatment.

11:30 SWI/SNF ATP-Dependent Chromatin Remodeling: Novel Avenues for Therapeutic Targeting

Mariela Jaskelioff, Ph.D., Investigator, Oncology, Novartis Institutes for BioMedical Research, Inc.

Epigenetic alterations play a key role in cancer, and epigenetic pathways present new avenues for therapeutic targeting in cancer. Through large scale functional studies targeting the epigenome, we uncovered a robust synthetic lethal relationship involving members of the SWI/SNF chromatin remodeling complex. Cancer cells suffering loss of BRG1, an ATP-dependent subunit of the SWI/SNF complex, are exquisitely dependent on the closely related but distinct SWI/SNF catalytic subunit BRM. BRM is therefore an attractive therapeutic target in BRG1-mutant cancers.

12:00 pm Who Will Benefit from Epigenetic Drugs?

Dominique Verhelle, Ph.D., MBA, Director, Epigenetics, Tumor Cell Biology, Oncology Research Unit, Pfizer, Inc.

One of the problems the industry involved in epigenetic drug discovery currently faces is to identify and to expand the use of the specific inhibitors. Since tumor response to an epigenetic inhibitor may be independent of target expression, mutational status and substrate levels, different approaches may be required to identify responder patients. This presentation will focus on precision medicine approaches applied to epigenetic targets.

12:30 Session Break

 12:40 Luncheon Presentation: Creating Predictive Disease Models Using Knowledge Networks

Nikolai Daraselia, Ph.D., Director, Research, Elsevier

Drug induced cholestasis is a common liver toxicity resulting in reduced bile acid secretion – a potential adverse event in drug development.   A cholestasis disease model was developed predicting FGF 19/15 involvement in bile acid biosynthesis and regulation by FXR and PXR.  When FXR and PXR are up-regulated, bile acid biosynthesis is down-regulated resulting in drug-induced cholestasis.  Since this publication, FXR, PXR and FGF19/15 roles in drug-induced cholestasis have been clearly established. Discussion on the role of predictive molecular disease models in early discovery will be presented.

1:40 Refreshment Break in the Exhibit Hall with Poster Viewing


TARGETING NON-CODING RNA  

2:15 Chairperson’s Remarks

Leonard Lipovich, Ph.D., Associate Professor, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine

2:20 microRNA Dysregulation in Cancer

Carlo M. Croce, M.D., Professor and Chair, Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetic Program, The Ohio State University

2:50 Long Non-Coding RNA Genes Shift Human Breast Cancer Cells along the Apoptosis-Proliferation Axis

Leonard Lipovich, Ph.D., Associate Professor, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine

The ENCODE Consortium highlighted the extraordinary abundance of long non-coding RNA (lncRNA) genes in the human genome. We interrogated the estrogen-responsive lncRNA transcriptome of human estrogen receptor alpha positive breast cancer, pinpointing a set of estrogen-induced lncRNAs. Knockdown and overexpression of these lncRNAs, followed by five phenotypic assays indicated they have profound and reproducible phenotypic impacts on human breast cancer cell morphology and growth. These functional lncRNAs should be rationally targeted in cancer therapeutics.

3:20 The Impact of Rare Non-Coding Variants of Gene Expression and Disease

Stephen B. Montgomery, Ph.D., Assistant Professor, Pathology, Genetics & Computer Science, Stanford University School of Medicine

Recent and rapid human population expansion has led to an excess of rare genetic variants that are expected to contribute to an individual’s genetic burden of disease risk. Large-scale sequencing studies have highlighted an abundance of rare, deleterious variants within protein-coding sequences. However, in addition to rare protein-coding variants, rare non-coding variants are likely enriched for functional consequences. I will highlight investigations of individual, family and population transcriptomes to identify the extent and impact of rare non-coding variants.

3:50 Selected Poster Presentation: From Public Repositories to Molecular Biomarkers Using Cloud Computing: Prostate Cancer-Specific lncRNAs

Subha Srinivasan, Ph.D., Core Faculty Scientist, Bioinformatics, Institute of Bioinformatics and Applied biotechnology

4:20 Valentine’s Day Celebration in the Exhibit Hall with Poster Viewing

 

5:20 Breakout Discussions in the Exhibit Hall 

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Precision Medicine Approaches Applied to Epigenetic Targets 

Dominique Verhelle, Ph.D., MBA, Director, Epigenetics, Tumor Cell Biology, Oncology Research Unit, Pfizer, Inc.     

  • What are current strategies to expand indications for epigenetic therapies?
  • What are the pitfalls to avoid ?
  • When is target expression not the best indicator for predictive response?
  • When are target silencing experiments misleading the prediction for predictive response?

Challenges Surrounding Biomarker Discovery for Novel Epigenetic Inhibitors 

Helai Mohammad, Ph.D., Investigator, Cancer Epigenetics DPU, Oncology R&D, GlaxoSmithKline 

  • What are the critical limitations in identifying biomarkers for novel epigenetic inhibitors?
  • What measures are being taken to overcome these issues?
  • What are clear-cut and feasible opportunities?

Transcriptomics to Therapeutics: Bridging the lncRNA Divide 

Leonard Lipovich, Ph.D., Associate Professor, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine 

  • Have exomes and RNA-Seq hindered, rather than helped, lncRNA disease genomics?
  • How can we proceed from disease lncRNA discovery, in GWAS and functional studies, to translational therapeutics?
  • Which of the currently known lncRNA mechanisms present the best opportunities for therapeutic targeting?
  • What are the limitations of animal models for studying lncRNA function, in view of lncRNA evolutionary non-conservation?
  • In the absence of a "national institute of RNA" or lncRNA study sections at the NIH, can pharmaceutical companies drive clinical-translational work in this field through academic-industry partnerships?
 

6:30 Close of Day



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