Sunday, March 27
5:00-6:00 pm Conference Pre-Registration
Monday, March 28
7:30-8:30 am Conference Registration and Morning Coffee
8:30-8:40 Welcoming Remarks from Conference Director
Julia Boguslavsky, Executive Director, Conferences, Cambridge Healthtech Institute
microRNA in Biomarker and
Diagnostic Development
8:40-8:45 Chairperson’s Opening Remarks
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
8:45-9:10 microRNAs as Diagnostics and Therapeutics in Cancer
Frank Slack, Ph.D., Professor, Department of Molecular, Cellular and Developmental Biology, Yale University
microRNAs are small non-coding RNAs that regulate gene expression to control important aspects of development and metabolism such as cell differentiation, apoptosis and lifespan. let-7 encodes a microRNA implicated in human cancer. Specifically, human let-7 is poorly expressed or deleted in lung cancer, and over-expression of let-7 in lung cancer cells inhibits their growth, demonstrating a role for let-7 as a tumor suppressor in lung tissue. let-7 is expressed in the developing mammalian lung and regulates the expression of important oncogenes implicated in lung cancer, suggesting a mechanism for let-7’s involvement in cancer. We are focused on the role of let-7 and other oncomiRs in regulating proto-oncogene expression during development and cancer, and on using miRNAs to suppress tumorigenesis.
9:10-9:35 microRNAs: Biomarkers for Cancer Therapy
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
A single microRNA can impact hundreds of targets and can affect pathways controlling oncogenic processes. Data will be presented illustrating how using microRNA can impact cancer treatment decision making, the validation of microRNAs associated with resistance and/or sensitivity to chemotherapy and targeted therapy and how microRNAs could be used as therapeutics.
9:35-10:00 Developing miRNA Mimics and Biomarkers
Lee P. Lim, Ph.D., Research Fellow, Sirna Therapeutics, Merck Research Labs
Progress in understanding the biology of microRNAs has opened up a new area for oligonucleotide therapeutics, where working with ~22nt RNAs that can regulate hundreds of genes presents novel challenges and opportunities. I will describe our work exploring structures and chemistries for miRNA mimetics, as well as work on the use of miRNAs as plasma biomarkers.
10:00-10:25 Multiplexing microRNA and Protein Expression Analysis for Cancer Diagnostics
Lorenzo F. Sempere, Ph.D., Research Assistant Professor of Medicine, Department of Medicine, Dartmouth-Hitchcock Norris Cotton Cancer Center
Visualization of microRNA expression within individual cells by in situ hybridization provides an independent tool to clinically validate results of high-throughput expression profiling experiments. Here we describe a rapid and sensitive fluorescence-based assay with multiplexing capability for co-detection of microRNA and clinically relevant protein markers on formalin-fixed paraffin-embedded specimens. We provide several examples in which the cancer cells, and supportive and/or reactive microenvironment elements, are the principal source of microRNA deregulation in solid tumors. We discuss implementation of a fully automated platform from detection to expression analysis of selected biomarkers for high-throughput microRNA-based diagnostic applications.
10:25-11:00 Networking Coffee Break
Technology Showcase
Sponsored by
 11:00-11:15 A Comprehensive 3’UTR Reporter System for High-Throughput miRNA Target Validation and Screening
Patrick Collins, Ph.D., Director, R&D, SwitchGear Genomics
microRNAs are important regulators of gene expression. To study miRNA-UTR interactions, we have created a genome-wide collection of human 3’UTR luciferase reporter vectors along with synthetic biosensor reporter vectors for every miRNA in the human genome. The 3’UTR reporters are available both in plasmids and lentivirus format for optimal delivery into many different cell lines. In this presentation we demonstrate how these vectors can be used to validate miRNA targets identified by prediction algorithms or other experimental methodologies.
Sponsored by
 11:15 -11:45 The nCounter System: A Truly Digital, Amplification-Free Platform for miRNA Quantification
Stephen Jackson, Ph.D., Principal Field Application Scientist, NanoString Technologies
The nCounter platform provides a novel method for quantifying miRNAs. Briefly, miRNAs are tagged, hybridized with fluorescent sequence-specific barcodes, imaged and then counted. Complete human or mouse miRNAomes are analyzed with 100ng total RNA in a single tube-assay. This method produces results that are extremely reproducible, allowing detection over a wide dynamic range and sensitive determination of small-fold changes.
Sponsored by
 11:45 am-12:00 pm Using IPA to Explore microRNA Impacts on Molecular Mechanisms of Disease
Dana L. Abramovitz, Ph.D., Product Manager, Ingenuity Systems, Inc.
In the field of microRNA research, identifying biologically relevant targets is a challenge. We prioritize mRNA targets and understand their contribution to disease progression by applying biological information using IPA®’s new microRNA Target Filter.
Sponsored by
 12:00-12:15 MicroRNA Expression Profiling using TaqMan® qPCR Technologies
James Hurley, Ph.D., Staff Scientist, Life Technologies Corporation
Expression profiling across large sample sets is a key method for discovering biomarkers associated with disease states. TaqMan® MicroRNA Assays, the gold standard for characterizing miRNA expression, are available in a variety of formats to meet the needs of differing study designs. To meet the needs of these large study sets, Life Technologies is launching a new format addressing the practicality of interrogating large miRNA panels seamlessly across many samples. Utilizing the OpenArray® platform, we present data from this new approach which includes all 758 TaqMan® assays currently available on two TaqMan® Array MicroRNA Cards and places them on a single OpenArray® plate in triplicate. Using this high density platform, it becomes practical to screen the full panel of miRNAs on up to 36 samples per day. This enables genuine high throughput profiling using qPCR. The workflow makes use of the existing Megaplex™ Primer Pools and assay designs are identical to those available on the TaqMan® Array MicroRNA Cards and in individual tubes. When considering the next step of validation and eventual biomarker signature utilization, this greatly simplifies the transfer of biomarker panels discovered using this profiling approach to more traditional 96- and 384-well plates or custom TaqMan® Array Cards. We present performance data for this new profiling platform and discuss its potential uses, including profiling using blood plasma samples.
Sponsored by
 12:15-12:30 Screening 1200 miRNAs with a Single Real-Time PCR Run with the SmartChip System
David Ginzinger, Ph.D., VP Genomics Research and Applications, Wafergen
The SmartChip System combines the high-throughput of microarrays with the power of real-time PCR to provide the unique flexibility to perform gene expression discovery, validation and screening on a single platform. The SmartChip Cycler can process a SmartChip Panel to perform >1200 assays in quadruplicate on one sample in just over 2 hours, or the same system can profile tens to hundreds of genes and from hundreds to several samples, respectively. The SmartChip Human microRNA Panel assesses the expression of 1200 human microRNA species, based on miRBase 16, in quadruplicate. The pre-optimized primer pairs have been selected using strict bioinformatics criteria to provide single base discrimination, high sensitivity and reproducible amplification.
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12:30-2:00 Lunch on Your Own
microRNA in Biomarker and Diagnostic
Development (continued)
2:00-2:05 Chairperson’s Opening Remarks
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
2:05-2:30 Prognostic Value of miRNAs in Colorectal Cancer
Upender Manne, Ph.D., Associate Professor, Pathology, University of Alabama at Birmingham
Although promising results from experimental models are available, the utility of miRNAs should be validated in order to develop a miRNA-based therapy for colorectal cancers (CRCs). We have demonstrated that miRNAs are stable in archival CRC samples stored for up to 28 years, and analyses of a panel of six miRNAs suggest that, after treatment for CRC, patients with higher levels, specifically miRNA-21 and miR-106a, had an increased risk of death. However, for African-American patients, but not for Caucasians, the presence of higher levels of miR-181b and miR-203 indicated a poorer prognosis. Further prospective validation is required prior to application in oncologic practice.
2:30-2:55 Nanopore-Facilitated Single Molecule Detection of Circulating microRNAs in Lung Cancer Patients
Li-Qun Andrew Gu, Ph.D., Associate Professor, Biological Engineering and Dalton Cardiovascular Research Center, University of Missouri
Developing new methods for lung cancer screening and early diagnosis is a critical issue for saving lung cancer patients’ lives. microRNAs (miRNAs) are small regulating RNA molecules that have been recognized as cancer biomarkers. We developed a nanopore sensor that is combined with a programmable oligonucleotide probe for selective and sensitive single molecule detection of miRNAs in lung cancer patient plasma samples. The sensor also demonstrated ability to discriminate miRNAs containing single nucleotide differences. This simple, sensitive, label-free technique requiring no amplification for miRNA detection has the potential for noninvasive and cost-effective early diagnosis of lung cancer.
2:55-3:20 microRNA Signatures and Roles in Prostate Cancer Progression
Cassandra Belair, Ph.D., Researcher, Urology, University of California, San Francisco
To test the global role of miRNAs in prostate cancer progression, we have crossed a prostate specific cre to PTEN- and DGCR8-conditional knockout mice. The loss of DGCR8 alone had no phenotype, while the loss of PTEN resulted in progression through hyperplasia, dysplasia, and microinvasion, which was blocked with their simultaneous loss. Expansion of basal-like cells was also blocked in the PTEN-DGCR8 double knockouts. An analysis of miRNAs in the plasma of human prostate cancer patients identified miRNA signatures associated with risk for progression. We are evaluating the functional roles of these miRNAs in progression using our in vivo model.
3:20-4:20 Networking Refreshment Break in the Exhibit Hall with Poster Viewing
4:20-4:45 Extracellular microRNA: A New Source of Biomarkers
Kai Wang, Ph.D., DABT, Senior Research Scientist, Institute for Systems Biology
microRNAs are small, non-coding RNAs that play an important role in regulating various biological processes in cells. Recently, some miRNAs have also been found in extracellular space. We examined the presence of miRNAs in a variety of normal human body fluids, from tears to breast milk, with the goal of assessing the distribution of miRNAs and examining the potential use of miRNAs as biomarkers. Our results indicate that miRNAs are present in all fluids tested and show distinct compositions in different fluid types. As an example, with a limited number of urine samples from individuals with several physiopathological conditions, we demonstrated the potential for using changes in the urine miRNA spectrum as biomarkers. This finding suggests the possibility of using the levels of specific miRNAs in body fluids to detect various pathological conditions.
4:45-5:10 microRNA and Thyroid Cancer
Honey Reddi, Ph.D., Assistant Professor, Medicine, Mayo Clinic
Thyroid cancer accounts for 96% of endocrine malignancies affecting about 3 million individuals in the U.S. Pre-operative assessment of thyroid nodules by currently used cytological methods poses a significant clinical challenge due to a 20% non-diagnostic rate. This results in unnecessary surgical intervention, wherein only 8-17% of cases are malignant, thereby prompting the need for additional methods of detection. We have identified a panel of miRs that is currently being tested for its potential to be used as a robust clinical assay for pre-operative diagnosis of malignancy and non-invasive follow-up of thyroid cancer patients. Also, some of the mechanisms by which these individual miRs are differently regulated will be discussed.
5:10-5:35 Towards Enhancing the Shelf-Life of ex vivo Stored Therapeutic Blood Cells: Study of microRNA-Target mRNA Interactions in Platelets
C.D. Atreya, Ph.D., Associate Director for Research, Office of Blood Research and Review, CBER, FDA
Recently we have shown that miRNAs do exist, and their profiles change in platelets during ex vivo storage. Here we demonstrate selected miRNA-mRNA interactions that have relevance to the apoptotic pathway. Understanding these interactions would help facilitate pathways for developing strategies to enhance the shelf-life of the platelets, the most sought-after therapeutics in transfusion medicine.
5:35-6:30 Networking Reception in the Exhibit Hall with Poster Viewing