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Tuesday, March 5
7:45 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee
8:25 Chairperson’s Remarks
Seena K. Ajit, Ph.D., Assistant Professor, Pharmacology and Physiology, Drexel University College of Medicine
New Therapeutic and Technological Strategies
8:30 Exosome-Mediated miRNA Transfer and Its Role in Pain
To decipher the role of differentially expressed circulating miRNAs in blood samples from patients with Complex Regional Pain Syndrome, we investigated exosome-mediated information transfer. We characterized the exosomes obtained from cell culture media with and without inflammatory stimulus and extended the studies to patient samples to investigate changes in exosomal content in response to inflammation and chronic pain. In addition to miRNAs, alterations in exosomal mRNA and proteins were also studied.
9:00 Talk Title to be Announced
Henrik Ørum, Ph.D., MSc, CSO & Vice President, Business Development, Santaris Pharma A/S
9:30 Coffee Break in the Exhibit Hall with Poster Viewing
10:10 microRNAs: Novel Target Class for Small Molecule Drug Discovery?
Pramod Pandey, Ph.D., Senior Research Investigator, Center for Proteomic Chemistry, Integrated Lead Discovery, Novartis Institute for Biomedical Research, Inc.
MicroRNAs (miRNAs) act in post-transcriptional gene silencing agents and are proposed to function in a wide spectrum of pathologies, including cancers, inflammation, cardiovascular and viral diseases. This presentation describes strategies employed at NIBR for discovering small molecule modulators of disease relevant miRNAs in high-throughput screens. Data will be presented for a number of targets including primary assay development and HTS performance as well as downstream assays to elucidate mechanism of action.
10:40 Harnessing the Power of Small RNAs in Vector-Mediated Therapeutics
Benjamin tenOever, Ph.D., Fishberg Professor of Medicine, Microbiology, Mount Sinai School of Medicine
A remaining challenge in harnessing the potential of small RNA therapeutics is the ability to deliver robust levels of functional small RNAs specifically to a tissue of interest. In an effort to address this challenge, we exploit endogenous microRNAs to control the tropism of engineered RNA-based vectors and use the vectors themselves as vehicles to generate specific short interfering RNAs.
11:10 Pre-Clinical Development of a Tumor Suppressor miRNA
David Brown, Ph.D., Director, Research, Mirna Therapeutics
miR-34 is a small RNA that functions within the p53 pathway and suppresses tumor development by regulating the expression of more than twenty oncogenes. We have developed a mimic of miR-34 that when formulated with a liposomal delivery technology and injected into the tail veins of tumor-bearing mice causes complete regression of liver tumors and significant inhibition of other tumor types. IND-enabling toxicology studies have revealed that the miR-34-based therapeutic candidate is well-tolerated in non-human primates and rodents and a Phase I clinical trial is scheduled to begin in early 2013.
11:40 Implementing microRNA Biomarkers for Non-invasive Diagnoses of DiseasesThomas Brefort, Ph.D., Vice President, Biomarker Development & Services, Comprehensive Biomarker CenterImplementing microRNA Biomarkers for Non-invasive Diagnoses of Diseases microRNA biomarkers non-invasively measured from the circulation either in the cell-free serum/plasma or in the cellular fraction provide complementing information on the pathological condition at the site of disease and on the immune system´s responses to it, respectively. Teaming up with clinicians in various disease areas we have conducted broad screening studies. We successfully explored diagnostic, differential diagnostic, therapy monitoring and patient stratification scenarios. We will present case studies demonstrating the high potential of microRNA-biomarkers for non-invasive diagnosis of diseases.
12:10 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
microRNAs as Biomarkers and in Diagnostics
1:40 Chairperson’s Remarks
Lorenzo F. Sempere, Ph.D., Research Assistant Professor, Department of Medicine, Geisel School of Medicine at Dartmouth
1:45 Extracting Contextual microRNA Information for Cancer Diagnostics
Cancer cell clonal diversity, tissue heterogeneity and the tumor microenvironment influence the efficacy of current cancer treatments. Detailed cellular and molecular characterization of altered microRNA expression in tumor lesions provides a unique opportunity to translate scientific knowledge into accurate clinical information. Using tissue slide-based morphology-driven multiplex assays within a CLIA-certified environment, we have identified cell type-specific microRNA changes in breast, lung and pancreatic cancer. I will present examples in which this contextual information improves the interpretative power of microRNA-based diagnostic and prognostic applications.
2:15 miRNA-Target Site SNPs as Predictors of Cancer Risk and Treatment Response
David W. Salzman, Ph.D., Scientist, Department of Therapeutic Radiology, Yale School of Medicine
miRNAs inhibit gene expression by annealing to complementary elements in a target mRNA. Therefore, sequence variants can alter miRNA function by creating or destroying target sites, leading to a myriad of diseases. Here we will discuss miRNA-target site polymorphisms identified by our laboratory that associate with an increased risk for developing cancer and appear to govern tumor biology and confer altered response to therapy.
2:45 Presentation to be Announced
3:15 Refreshment Break in the Exhibit Hall with Poster Viewing
3:50 Direct Detection of Circulating miRNAs
Sumedha Jayasena, Ph.D., Vice President, Technology & Therapeutic Development, Therapeutics, SomaGenics
SomaGenics has developed a new method called miR-IDirect that allows the direct release, enrichment and detection of miRNAs from plasma without prior isolation of total RNA. This novel technology will have an impact on the development and implementation of circulating miRNA-based biomarkers in various disease settings, including cancer.
4:20 Circulating miRNAs as Biomarkers: How Far Have We Made It?
Igor Mikaelian, M.D., D.V.M., MSc, DACVP, Pathologist, Pharmacology, AbbVie, Inc.
Quantification of miRNAs in body fluids is the latest biomarker frontier in drug safety assessment. The presentation will review the microRNAs that have been proposed as biomarkers of organ toxicity, with a special emphasis on vascular, cardiac and hepatic toxicity. The discussion will focus on biomarker identification strategies and the pre-clinical validation plans for clinical implementation.
4:50 Enzymatic and Non-Enzymatic Quantitation of Circulating MicroRNAs
Dominik M. Duelli, Ph.D., Assistant Professor, Department of Cellular and Molecular Pharmacology, Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science
Accurate enzyme-based quantitation of miRNAs is compromised by inhibitors that copurify with RNA. We evaluated approaches for blood collection, extraction, and enzyme choice to promote exact quantitation. Alternatively, we introduce the use of a non-enzymatic method that employs SmartFlareTM RNA Detection probes for the specific and sensitive quantitation of plasma miRNAs requiring minimal processing within an hour of venipuncture.
5:20 End of Conference
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