TUESDAY, MARCH 23
7:30-8:00 am Morning Coffee
8:00-8:05 Chairperson’s Opening Remarks
8:05-8:30 Title to be Announced
Hannele Ruohola-Baker, Ph.D., Professor, Biochemistry, University of Washington
8:30-8:55 microRNAs Control Gene Expression during Astrocyte Activation
Noam Shomron, Ph.D., Head, Tel Aviv University Genome High-Throughput Sequencing Center; Principal Investigator, Cell and Developmental Biology, Tel Aviv University
Astrocytes are a sub-type of glial cells in the central nervous system which commonly envelope synapses made by neurons. Lipopolysaccharides (LPS) are large molecules found in the outer membrane of Gram-negative bacteria that act as endotoxins and elicit strong immune responses in animals. We performed high-throughput analysis of microRNAs expressed during astrocyte exposure to LPS. We identified critical microRNAs dominantly controlling the astrocytic response, their unique gene targets and novel cellular pathways affected by this process. Our results lead to better understanding of the mechanisms governing asctocyte activation upon particular bacterial infection and will lead to improved therapeutics.
8:55-9:20 Deregulated mRNA/miRNA Expression Networks in Dopamine Neurons and Parkinson’s Disease
Kai-Christian Sonntag, M.D., Ph.D., Assistant Professor, Psychiatry (Neuroscience), Harvard Medical School
In late-stage sporadic Parkinson’s disease (PD) dopamine (DA) neurons display a profound dysregulation of genes that are part of signaling pathways in PD pathogenesis. Here, we determined if this dysregulation was associated with deregulated miRNAs. miRNA profiling on laser-microdissected DA neurons from normal individuals and PD patients revealed distinct miRNA expression patterns with predominant upregulation in PD. Furthermore, correlation analysis using mRNA arrays and computational target prediction delineated a set of “PD-specific” miRNAs that were associated with the dysregulated gene expression network in PD DA neurons. These results imply that miRNAs might play a role in regulatory gene expression processes associated with PD.
9:20-9:45 Herpes Simplex Virus miRNAs in Productive and Latent Infections
Donald M. Coen, Ph.D., Biological Chemistry & Molecular Pharmacology, Harvard Medical School
Herpes simplex viruses (HSV) 1 and 2 infect a very large proportion of the human population, and cause diseases including cold sores, corneal keratitis, and genital lesions and rarer life-threatening conditions such as encephalitis. HSV-1 and -2 establish latent infections in sensory neurons from which the viruses can reactivate to cause recurrent disease and transmit to new hosts. During latency, expression of viral genes active during productive infection is repressed. Currently available drugs such as acyclovir can treat or suppress recurrent disease, but do not cure latent infections. HSV-1 and -2 encode a score or more of microRNAs, some of which are expressed more abundantly during productive infection, and others that are expressed more abundantly during latent infection. Certain of these microRNAs can target mRNAs encoding proteins important for regulation of viral gene expression, which may help explain both the high activity of viral gene expression during productive infection and its repression during latent infection. The results have raised the possibility that latent HSV infections can be addressed by targeting HSV microRNAs.
9:45-10:45 Coffee Break with Exhibit and Poster Viewing
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 10:45-11:15 Discovery of miRNA-Based Biomarkers for Colon Cancer
Søren Møller, Ph.D., Vice President, Product Development, Exiqon A/S
Abnormal expression of microRNAs (miRNAs) in cancer implies that these small ~22-nucleotide molecules play a role in oncogenesis, and miRNAs may comprise a novel class of diagnostic and prognostic biomarkers. This talk will focus on use of microRNAs detected in FFPE tissue and plasma as novel biomarkers for colon cancer.
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Thomas Schmittgen, Ph.D., Associate Professor, Division of Pharmaceutics, College of Pharmacy, Ohio State University
Sponsored by
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11:45 am-12:00 pm miRNA Biomarker Profiling from Blood: A Promising Approach for Non-Invasive Diagnostic Testing
Peer Staehler, VP Marketing and CSO, febit, Inc.
Automated miRNA biomarker profiling using febit’s microfluidic microarray technology is a promising approach for blood-based diagnostic tests. Requiring minimal sample amounts, this sensitive high-throughput Biochip technology makes it possible to measure marker miRNAs and develop predictive miRNA signatures from limited clinical sample material, such as blood or other body fluids, FFPE samples, fresh or frozen tissue. Our studies show that miRNA expression patterns, rather than single miRNAs, serve as biomarker signatures for the detection and classification of human diseases such as cancer.
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 12:00-12:30 Sustained Overexpression of miRNA Mimics using a Lentiviral Delivery System
Emily Anderson, Research Scientist, Thermo Scientific Genomics
miRNA mimics and inhibitors are frequently employed to better understand the contributions of these noncoding RNAs to cell physiology. Currently, the predominant method for overexpressing miRNAs involves transfecting synthetic mimics into target cells. To further expand the collection of tools available to researchers, we have recently developed a new lentiviral-based miRNA expression platform. Strategies used to optimize robust miRNA expression will be presented along with data describing their overall performance in mammalian cell culture models.
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12:30-2:00 Lunch on your own
2:00-2:05 Chairperson’s Opening Remarks
2:05-2:30 Developing miRNA Biomarkers and Therapeutics
Lee P. Lim, Ph.D., Research Fellow, Sirna Therapeutics, Merck Research Labs
2:30-2:55 Title to be Announced
Sterghios A. Moschos, Ph.D., Senior Scientist, Pfizer Global R&D
2:55-3:20 Mature miRNAs or Pre-miRNAs, Which is the Better Biomarker?
Dirk Dittmer, Ph.D., Associate Professor, Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, Center for AIDS Research, University of North Carolina at Chapel Hill
Mature miRNAs are derived from nuclear precursors. How are the levels of these two species correlated in human cancer, and would pre-miRNA detection perhaps be an easier biomarker from the point of assay development? Examples from lymphoma and sarcoma will be compared using real-time QPCR based and Illumina NextGen sequencing-based approaches.
3:20-3:45 microRNA Polymorphisms and the Future of Personalized Medicine
Prasun J. Mishra, Ph.D., Laboratory of Cancer Biology & Genetics, National Cancer Institute, National Institutes of Health
Referred to as the micromanagers of gene expression, microRNAs are evolutionarily conserved small non-coding RNAs. Polymorphisms in the microRNA pathway can influence gene regulation and are emerging as powerful tools to study the biology of diseases. Detection of microRNA-polymorphisms can potentially improve diagnosis, treatment and prognosis in patients and has profound implications in the fields of pharmacogenomics and
personalized medicine.
3:45-4:30 Refreshment Break with Exhibit and Poster Viewing
4:30-4:55 miRNA Biomarkers for Chemoresistance in Lung Cancer
Glen J. Weiss, M.D., Co-Head, Lung Cancer Unit, The Translational Genomics Research Institute (TGen); Director, Thoracic Oncology, TGen Clinical Research Services at Scottsdale Healthcare
Lung cancer is the most common cause of cancer-related deaths in the world. In the United States, over 90 million individuals are at risk for developing lung cancer and this disease is estimated to remain a major health problem for at least the next 50 years. For advanced disease, median survival is improved to roughly 12 months with systemic therapy. Efforts to improve outcomes for these patients have recently focused on enriching for clinical (e.g. histology) or molecular (e.g. tyrosine kinase mutation status) factors. Investigators are now applying microRNA (miRNA) expression profiling to samples with various clinical contexts in the search for theranostic biomarkers that may rapidly stratify patients to the appropriate treatment. In this presentation, data will be presented illustrating the potential of miRNAs to impact treatment decision making for lung cancer patients, including miRNAs associated with chemoresistance in non-small cell and small cell lung cancers.
4:55-5:20 miRNA and Array-Based DNA Methylation Profiles Associated with Clinical Response in Advanced Stage Ovarian Cancer Patients
Delia Mezzanzanica, Ph.D., Senior Researcher, Molecular Therapy Unit, Department of Experimental Oncology, National Tumor Institute, Italy
The still unfavorable statistics in epithelial ovarian cancer (EOC) patients reflects the largely unpredictable response to first-line treatment and the occurrence of relapse associated with broad cross-resistance to even structurally dissimilar drugs. In combination with genetic changes, epigenetics modifications may be involved in EOC initiation and progression; in particular, aberrant methylation at CpG-rich areas, such as hypermethylation in promoter regions, is a frequent inactivation mechanism also for miRNAs. To evaluate whether an imbalance of microRNAs expression could be involved in EOC chemoresistance we profiled a selected case material grouped on the basis of extent of debulking surgery, response to first-line treatment, and time to relapse for miRNA expression and quantitative methylation using Illumina platforms. Considering a fold change>5 and a FDR<0.01, 70 miRNA were identified, by class comparison analysis, as differentially expressed in normal surface epithelium versus EOC samples (miRNA involved in the epithelial to mesenchimal transition were among the most up-modulated in tumor samples), whereas 44 miRNAs differentially expressed at FDR <0.15 were identified in responder patients as compared to non responders (the majority of them localized on chromosome X and 14). We found patterns of DNA methylation able to distinguish tumors samples with different time to relapse. We also noticed that changes in methylation involve specific chromosome regions and might be associated with miRNA expression.
5:20-5:45 miRNA Profile as Biomarker in Colorectal Cancer
Manuel Valladares-Ayerbes, M.D., Medical Oncology, La Coruña University Hospital and Biomedical Research Institute
miRNAs have potential as diagnostic biomarkers and therapeutic targets in cancer. Our aim was to identify miRNAs with diagnostic value for circulating tumor cells (CTC) detection in periphereal blood from patients with colorectal cancer. In addition, different miRNA tumor profiles have been correlated with Kras status.
5:45-6:10 microRNA Profiling in Search of Product Biomarkers for Stored Blood Cells
C.D. Atreya, Ph.D., Associate Director for Research, Office of Blood Research and Review, Center for Biologics Research and Review, U.S. Food and Drug Administration
In transfusion medicine, ex vivo stored human packed red blood cells (PRBC) and Platelet Concentrates (PC) play a crucial role. To date there is no single in vitro biomarker for either stored PRBC or PC predictive of in vivo quality and function following their transfusion to human recipients. Here we report that microRNA profiling may provide some clues to address this issue.
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 6:15-7:30 Evening Cocktail Reception
Exiqon invites you to network with peers in a relaxed setting and enjoy hors d’oeuvres with light cocktails following the close of the conference programming. Open to conference delegates.
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