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microRNA: Targets and Tools for Therapeutic Development - Day 1


2013 Archived Content

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Sunday, March 3

1:30 pm Registration for Pre-Conference Short Course

2:00 – 5:00 pm Pre-Conference Short Course Computational Aspects of microRNA

Computational Analysis of Noncoding RNA

Tutor: Stefan Washietl, Ph.D., Scientist, Computational Biology, Massachusetts Institute of Technology

Using a Bioinformatics Resource Manager

Susan C. Tilton, Ph.D., Scientist, Computational Biology & Bioinformatics, Pacific Northwest National Laboratory

BioVLAB-MMIA: a Cloud Environment for microRNA and mRNA Integrated Analysis (MMIA) on Amazon EC2

Hyungro Lee, Ph.D., Pervasive Technology Institute, School of Informatics and Computing, Indiana University


 


*Separate Registration Required




Monday, March 4

7:30 am Registration & Morning Coffee

8:10 Chairperson’s Opening Remarks

Steffen Gay, M.D., Professor, Experimental Rheumatology, University of Zurich 

  

Therapeutic Potential  

8:15 microRNA Polymorphisms and the Future of Personalized Medicine

Prasun Mishra, Ph.D., Earl Stadtman Investigator Candidate, Center for Cancer Research, National Cancer Institute, NIH

Cumulative evidence now suggests that specific miRNAs and genetic variations interfering with miRNA function (miRNA polymorphisms) are involved in the prognosis and progression of a variety of diseases and can serve as biomarkers to predict drug response. Over expression or down regulation of a miRNA, and loss or gain of miRNA function due to miRNA polymorphisms can potentially affect expression of hundreds of genes and related pathways contributing to a drug resistant phenotype. Detection of prognostic-miRNAs and miRNA polymorphisms can potentially improve diagnosis, treatment and prognosis in patients and has profound implications in the fields of pharmacogenomics and personalized medicine.

Inflammation 

8:45 MiR-181b-Mediated Control of NF-kB in Acute and Chronic Inflammation

Mark W. Feinberg, M.D., Assistant Professor of Medicine, Cardiology, Brigham and Women’s Hospital

Endothelial activation and dysfunction have been linked to a variety of vascular inflammatory disease states including sepsis, atherosclerosis, diabetes, and rheumatoid arthritis, among others. Activation of NF-kB signaling has been implicated in physiological and pathological processes. This talk will highlight both published and unpublished findings on the role of a microRNA, miR-181b, that we identified as a critical regulator of NF-kB signaling in acute (sepsis) and chronic (atherosclerosis and asthma) inflammation disease models and in human subjects. Mechanistic studies will reveal how we uncovered miR-181b target gene, importin-alpha3 that regulates NF-kB nuclear accumulation. Innovative in vivo delivery strategies for miR-181b mimetics will be highlighted to target the vascular endothelium.

9:15 microRNAs in Diagnostics and Targeting Rheumatic Disease

Steffen Gay, M.D., Professor, Experimental Rheumatology, University of Zurich

By studying the pivotal role of synovial fibroblasts (SF) in rheumatoid arthritis (RA), we detected miR- 145 and 155 to be expressed in RASF and monocytes and eventually to be used with miR 223 for diagnostics in very early disease. In related work we could not induce arthritis in miR 155 ko mice. We reported also that mir-203 is a strong regulator of IL-6. Most interesting was that IL-6 was neither regulated by TLR-signaling nor proinflammatory cytokines such as IL-1 and TNFa, but by methylation in the promoter of the miR-203. Moreover, we further found that miR 18a enhances the IL-6 mediated production of the acute-phase proteins fibrinogen and haptoglobin in human hepatocytes. However, most promising is the targeting of miR 323 for the induction of TIMP-3 as an inhibitor of MMPs as well as IL-6 and TNFa.

9:45 Coffee Break in the Exhibit Hall with Poster Viewing

Firefly10:15 Streamlined microRNA Profiling for the Clinical Setting

Daniel C. Pregibon, Ph.D., CTO, Firefly BioWorks

Clinical adoption of microRNA biomarkers necessitates a robust method to profile large sample cohorts. Firefly BioWorks has developed FirePlex™, a high-throughput method of microRNA analysis for research and clinical settings. We use FirePlex™ to demonstrate extraction-free microRNA detection in crude cell lystates, fresh tissues, FFPE, and blood-based specimens.

NanoString 10:45 Digital Multiplexed miRNA Quantitation for Translational Research Studies Using nCounter TechnologyJoseph M. Beechem, Senior Vice President, Research & Development, NanoString TechnologiesNanoString’s miRNA expression tools allow researchers to digitally count hundreds of miRNAs from Human, Mouse, Rat and Drosophila genomes. Compatible with challenging sample types (e.g., FFPE, plasma, serum) nCounter miRNA Expression Assays can be utilized for biomarker discovery, validation, and retrospective-prospective studies. NanoString’s miRGE-technology, enables highly-multiplexed detection of both mRNAs and miRNAs simultaneously: a single tube expression assay for small RNAs and their regulated targets. Translational research studies with miRNAs will be highlighted.

11:15 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own


Cancer 

12:55 pm Chairperson’s Remarks

Alexander Pertsemlidis, Ph.D., Associate Professor, Pediatrics and Cellular & Structural Biology, UT Health Science Center at San Antonio

1:00 Creating Unique Mass Signatures for Label-Free and Quantitative Analysis of MicroRNA Biomarkers

Norman Chiu, Ph.D., Associate Professor, Chemistry and Biochemistry, University of North Carolina at Greensboro

With microRNA’s unique ability to post-transcriptionally regulate gene expression, microRNAs have been clinically associated with cancer and many other diseases. More than 1,700 human microRNAs have been reported. With their relative small sizes (19-25 nt), the analysis of specific microRNA poses a big challenge to the current methods for measuring nucleic acids. In this presentation, the development of a new mass spectrometric method that improves the accuracy for measuring specific microRNA biomarkers for glioblastoma is discussed.

1:30 P63/P73-Regulated microRNAs Control the Metastatic Dissemination

Benjamin Ory, Ph.D., Associate Professor, Therapy Primary Bone Tumor, Nantes Medical School, INSERM U957

Expression profiling allowed us to identify p63-regulated miRs potentially targeting the TGFβ pathway. These miRs repress TGFβRII and Smad4 principally and thereby interfere with metastasis dissemination. Preliminary data demonstrate that these miRs are regulated by both p63 and p73, and that they are able to repress the activation of the TGFβ pathway in vitro, and to regulate tumor cells dissemination in vivo. Taken together, these findings support the hypothesis that a p63/p73-regulated miR program mediates metastasis dissemination, in different type of cancer, through the regulation of the TGFβ pathway.

2:00 Causes and Consequences of microRNA Dysregulation in Cancer

Carlo M. Croce, M.D., Professor and Chair, Department of Molecular Virology, Immunology and Medical Genetics; Director, Institute of Genetics, Ohio State University

2:30 Refreshment Break in the Exhibit Hall with Poster Viewing

3:10 microRNA Regulation of Cell Viability and Drug Sensitivity in Lung Cancer

Alexander Pertsemlidis, Ph.D., Associate Professor, Pediatrics and Cellular & Structural Biology, UT Health Science Center at San Antonio

Lung cancer is the leading cause of cancer-related deaths, with the majority of deaths due to failed therapy from tumor drug resistance. Third-generation chemotherapeutic agents represent the standard first-line treatment for advanced small cell (SCLC) and non-small cell (NSCLC) lung cancer patients. Response rates are poor (20-40%) with a median survival of 8–10 months. In an unbiased and comprehensive approach, we have combined a high-throughput screening platform with a library of chemically synthesized microRNA mimics and inhibitors. We have used this platform to identify mimics and inhibitors that reduce cell viability in general, and those that specifically sensitize cells to taxanes, which add novel therapeutic tools for the treatment of lung cancer.

3:40 miRNAs Modulating Anticancer Drug Sensitivity in Ovarian Cancer Cells: Possible Therapeutic Applications

Erik Wiemer, Ph.D., Associate Professor, Medical Oncology, Erasmus University Medical Center/Daniel den Hoed Cancer Center

Initially epithelial ovarian cancer is responsive to chemotherapy, however, eventually patients relapse because of the development of drug resistance. We identified and functionally characterized miRNAs that affect the sensitivity for cisplatin. By modulating the expression levels of these miRNAs in epithelial ovarian cancer cells present in the ascites fluid of chemoresistant ovarian cancer patients, we re-sensitize tumor cells to cis/carboplatin.

4:10 A miR-371-3/367 Serum Test for the Diagnosis and Follow-Up of (Testicular) Germ Cell Cancer Patients

Leendert Looijenga, Ph.D., Head, Research Lab, Pathology, Erasmus University

A complete quality-controlled pipeline for detection of miR-371-3 and miR-302/367 in serum of germ cell cancer patients has been developed, based on magnetic bead-based purification and qPCR quantification. This Targeted Serum miRNA (TSmiR) test was applied to four independent serum sample series. TSmiR demonstrated a consistent and significant increase for miR-371-3 and 367 in serum of seminoma and nonseminoma patients. Compared to AFP and hCG, the TSmiR test performed better. Application of a combined AFP/hCG-TSmiR test correctly identified all patient serum samples with GCC, with only one false-negative case based on the TSmiR-test alone. In conclusion, a highly reproducible and informative serum test for patients with a GCC is described, suitable to be prospectively tested for diagnosis and follow-up of GCC patients.

4:45 Selected Oral Poster Presentations

5:15 Moderated Breakout Discussion Groups

Topic 1: microRNA Analysis in Tissue Specimens

Moderator: Lorenzo F. Sempere, PhD., Department of Medicine, Dartmouth University

Topic 2: Detection of Circulating microRNAs

Moderator: Sumedha Jayasena, Ph.D., Vice President, Technology & Therapeutic Development, Therapeutics, SomaGenics

Topic 3: microRNA Polymorphism

Moderator: Prasun Mishra, Ph.D., Earl Stadtman Investigator Candidate, Center for Cancer Research, National Cancer
Institute, NIH
                Discussion points: Mechanism of action, classification, miRNA-pharmacogenomics, promises to individualized medicine
 

Topic 4: microRNAs as Modulators of Anticancer Drug Sensitivity and Their Use in the Clinic

Moderator: Erik Wiemer, Ph.D., Associate Professor, Medical Oncology, Erasmus University Medical Center/Daniel den Hoed Cancer Center

6:15 Welcome Reception in the Exhibit Hall with Poster Viewing

7:15 End of Day



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