WEDNESDAY, MARCH 24
8:00-8:45 am Breakfast Presentation (Opportunity Available) or Morning Coffee
Contact Jon Stroup, Manager, Business Development, at jstroup@healthtech.com or 781-972-5483.
9:00-9:05 Chairperson’s Opening Remarks
9:05-9:30 Impact of miRNA in Cancer Stem Cell Chemoresistance
Jingfang Ju, Ph.D., Co-Director, Translational Research Laboratory, Department of Pathology, Stony Brook University Medical Center
Resistance to chemotherapy is one of the major reasons for the failure of anti-cancer therapy. Our group has focused on the roles of miRNAs in chemoresistance. We have recently discovered several miRNAs that are directly responsible for colon cancer stem cell resistance to chemotherapy. Our study provides new insights and potential novel strategies to sensitize tumor stem cells to chemotherapeutic treatment.
9:30-9:55 microRNA Regulation of Cancer Stem Cells and Therapeutic Implications
Liang Xu, M.D., Ph.D., Department of Radiation Oncology, Division of Cancer Biology, University of Michigan
Emerging evidence demonstrates that miRNAs are involved in cancer stem cell dysregulation. miRNAs play a critical role in carcinogenesis by regulating cell proliferation and apoptosis as oncogenes or tumor suppressors, respectively. Therefore, molecularly targeted miRNA therapy could be a powerful tool to correct the cancer stem cell dysregulation.
9:55-10:20 Do microRNAs Promote the Diversion from a “Luminal A” Lineage to a “Basal-like” Phenotype in Breast Cancer?
Bruce A. White, Ph.D., Professor, Department of Cell Biology, University of Connecticut Health Center
Luminal A is the most common subtype of breast cancer, displays robust expression of ERa, and confers a favorable prognosis. In contrast, Basal-like cancers represent a subtype of “triple-negative” (TN) breast cancer that is more aggressive, of higher grade and confers a poorer prognosis. We have shown that miR-206, which is overexpressed TN tumors, coherently targets mRNAs encoding ERa, GATA3 and the coactivators, SRC1 and SRC3. EGFR is frequently overexpressed in Basal-like cancer, and we find that EGF promotes the loss of a Luminal phenotype in MCF7 cells, in part, through the upregulation of miR-206 expression. We are currently examining other microRNAs whose expression is stimulated by EGFR signaling and which promote a diversion of the Luminal lineage towards a more stem-like and mesenchymal-like Basal phenotype.
10:20-11:20 Coffee Break with Exhibit and Poster Viewing
Sponsored by 11:20-11:50 miRNA Profiling in Context: miRNA and mRNA Profiling of the NCI-60 on the Agilent Microarray Platform
Stephanie Fulmer-Smentek, Ph.D., RNA Applications, R&D Group Manager, Biological Systems Division, Agilent Technologies
Profiling of mRNAs and miRNAs in cancer can help elucidate regulatory influences and determine potential interactions with cancer attributes such as cell growth and drug response. The NCI-60, a set of cancerous cell lines derived from nine different tissues, provides a model system for these analyses. I will present new NCI-60 profiling data, using the Agilent Gene Expression and miRNA microarray platforms. The data demonstrate high reproducibility across replicates for both platforms and generally similar profiles across the cell lines. I will also discuss a few of the lessons learned from this study.
Sponsored by 11:50 am-12:20 pm nCounter™ Analysis System: A Complete Solution for Detecting and Counting Large Sets of Target miRNA, mRNA, and DNA Molecules in Biological Samples Using Color Coded Tags Stephen Jackson Ph.D., Field Application Scientist, NanoString Technologies, Inc. The nCounter Analysis System detects and counts individual nucleic acid molecules. Over 500 different nucleic acid species can be measured in a single hybridization reaction without the need for amplification. The novel molecular barcoding system provides digital counting of nucleic acid molecules in a variety of input materials including formalin-fixed paraffin-embedded (FFPE) tissues, cell lysates, and blood. These features make the nCounter Analysis System well suited to measure multi-gene expression signatures, validate transcriptional networks and detect mRNA fusion-transcript biomarkers. Current efforts to expand the platform to other applications, such as miRNA expression profiling and detecting variations in genomic copy number, will be presented.
Sponsored by
12:20-12:35 High-Throughput Functional Screening for miRNA Targets Patrick Collins, Ph.D., Director of Research and Development, Switchgear Genomics An increasing number of studies have highlighted the importance of microRNAs in normal and pathological processes. We have created a genome-wide collection of 12,000 3’ UTR luciferase reporters to study the functional role of microRNAs. We will demonstrate how this collection can be used to validate miRNA targets identified by prediction algorithms or other experimental methodologies by performing an extensive screen of putative miR-122 targets as a model. In addition to identifying several novel targets, our assay proved to be specific, dose-responsive and correlative with other methodologies.
Sponsored by 12:35-12:50 Seq-Array - miRNA Discovery and Profiling Using a Customizable Workflow Christoph Eicken, Ph.D., Head of Technical Services - Microarrays, LC Sciences
Current miRNA profiling methods rely on the limited sequence information available, hence the focus on a few model species. Seq-Array is a customized solution high-throughput genome-wide miRNA profiling to overcome these limitations. It combines and leverages three technologies: the latest deep sequencing technology, advanced bioinformatics, and μParaflo™ custom microarrays. This talk will present the workflow and a case study with 777 newly discovered miRNAs.
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12:50-2:00 Lunch on your own
2:00-2:05 Chairperson’s Opening Remarks
2:05-2:30 Tapping into the microRNA Network: Engineering Target Sites for Experimental and Therapeutic Applications
Brian D. Brown, Ph.D., Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine
In recent years progress has been made to uncover the factors that influence microRNA:target interactions. We are now applying this information to develop strategies for exploiting as well as modulating endogenous microRNAs. By modifying gene transfer vectors to encode synthetic microRNA target sites, we can design systems that are subject to microRNA control, or, conversely, can inhibit the activity of a microRNA. This approach is being used to improve vector targeting for gene therapy, or to provide a means for studying microRNA function.
2:30-2:55 microRNA Manipulation as a Therapeutic Strategy for Cardiovascular Disease
William S. Marshall, Ph.D., President and Chief Executive Officer, miRagen Therapeutics
Cardiovascular disease is the number one global killer and represents a major area of unmet medical need. Alterations in specific microRNAs have been observed in several cardiovascular disease models and human clinical samples, providing an exciting potential for therapeutic intervention. An update on relevant microRNA identification and efforts toward therapeutic development will be presented.
2:55-3:20 Therapeutic microRNA Strategies for Breast and Ovarian Cancers
Lin Zhang, M.D., Research Assistant Professor, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine
3:20-3:45 Development of LNA-antimiRs to Target Pathogenesis-Associated microRNAs
Morten Lindow, Ph.D., Group Leader, Integrative Systems Biology, Santaris Pharma A/S
microRNAs have emerged as promising molecular targets for intervention in a wide variety of diseases. This talk will focus on the utility of Locked Nucleic Acid (LNA)-modified oligonucleotides in microRNA silencing in vitro and in vivo. We will report on the progress of our microRNA therapeutics programmes and technology platform in general. Specifically we will report on the efficacy of antimiR-122 in the treatment of chronically HCV-infected primates.
3:45 Close of Conference