WEDNESDAY, MARCH 25
Breakfast Roundtable Discussions & Technology Showcase
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8:00-9:00 Breakfast Roundtable Discussions
microRNA Profiling (Moderator: Francois Vigneault, Ph.D., Harvard Medical School) microRNA in Cancer (Moderator: Frank Slack, Ph.D., Yale University) microRNA in Development (Moderator: Richard Gregory, Ph.D., Harvard Medical School) microRNA in Disease (Moderator: Elena Vigorito, Ph.D., The Babraham Institute) microRNA for Diagnostics (Moderator: Søren Møller, Ph.D., Exiqon A/S) microRNA for Therapeutics (Moderator: To be Announced)
9:00-9:30 Discovery of miRNA-Based Biomarkers for Cancer
Søren Møller, Ph.D., Vice President, Research & Development, Exiqon A/S
Abnormal expression of microRNAs (miRNAs) in cancer implies that these small ~22-nucleotide molecules play a role in oncogenesis. Therefore miRNAs may comprise a novel class of diagnostic and prognostic signatures. This talk will focus on examples of using microRNA for cancer classification, prognosis and treatment selection.
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9:30-10:15 Coffee Break with Exhibit and Poster Viewing
microRNA Biomarkers for Diagnostics
10:15-10:20 Chairperson’s Opening Remarks
Søren Møller, Ph.D., Vice President, Research & Development, Exiqon A/S
10:20-10:45 microRNA and the Prognosis and Diagnosis for Age-dependent Frailty
Eugenia Wang, Ph.D., Gheens Endowed Chair in Aging, University of Louisville
The functional impact of microRNA in determining our systemic well-being, from individual signaling pathways to the operation of tissue systems, provides us the key such that we can use their presence or absence to assess a physiological state before changes of their target genes’ expression sets in. To this end, we have identified key up-regulated microRNAs in the replicatively senescent fibroblasts, aging mouse liver, and the peripheral blood mononucleocytes (PBMC) of Alzheimer’s disease patients. Through bioinformatic data mining and complementary global proteomic profiling, we find that the up-regulated microRNAs affect target genes primarily in signaling pathways of DNA repair, oxidative defense, and intermediate metabolism, among others. In particular, our results show two up-regulated microRNAs in the middle-aged mouse liver, thus presenting themselves as candidate pre-symptomatic biomarkers for aging. In brief, our results so far have shown that key up-regulated microRNAs can be used as: 1. prognostic/diagnostic epigenetic biomarkers for age-dependent frailty and diseases; and 2. therapeutic leads to modulate the expression of genes key to maintaining the signaling actions of oxidative defense, DNA repair, and intermediate metabolism.
10:45-11:10 microRNAs as Novel Prognostic Biomarkers in Colorectal Cancer
Jingfang Ju, Ph.D., Associate Professor and Co-Director, Translational Research Laboratory, Department of Pathology, Stony Brook University Medical Center
Our group first reported that a number of miRNAs were potentially regulated by p53 tumor suppressor gene. The expression of miRNAs was systematically analyzed in archived FFPE colorectal specimens and we showed that miRNAs are stable and can be used for biomarker discovery. We also reported that several miRNAs were closely associated with clinical prognosis of colorectal cancer.
11:10-11:35 microRNA Expression Profiles Associated with Prognosis and Therapeutic Outcome in Colon Adenocarcinoma
Aaron J. Schetter, Ph.D., M.P.H., Postdoctoral Fellow, Laboratory of Human Carcinogenesis, National Cancer Institute
We examined microRNA expression levels in colon adenocarcinoma and paired noncancerous tissue in two independent cohorts. High expression of miR-21 in colon tumors predicts poor cancer-specific mortality in both the NCI-Maryland and Hong Kong cohorts, independent of other clinical covariates. This association was also observed when the analysis was restricted to stage II cases, indicating that miR-21 expression may be a useful biomarker for early stage colon cancer. High miR-21 expressional predicted a poor therapeutic outcome to fluorouracil-based chemotherapy. These results were found and validated using two independent cohorts from different geographic and cultural areas demonstrating that these associations are likely representative of the majority of sporadic colon adenocarcinomas. If altered miR-21 expression is in part causal to carcinogenesis, miR-21 has potential as both a biomarker and therapeutic target for colon cancer.
11:35-12:00 microRNA for Diagnostics and Therapeutics
Dalia Cohen, Ph.D., Chief Scientific Officer, Rosetta Genomics, Inc.
In cancer, different microRNA expression patterns have been shown to be associated with different tumor types. Due to their high tissue specificity and their involvement in different biological processes, microRNA can lead to the development of diagnostic tools and a novel class of therapeutic targets. Hepatocellular cancinomoma (HCC) is the fifth most common type of liver cancer in the world and new therapeutic interventions are of highly unmet medical need. To identify potential microRNA-based drug targets for the treatment of this tumor, microRNAs that were found to be differentially and highly expressed in HCC samples were chosen as candidate drug targets. Specific antisense oligonucleotides that targeted these microRNAs and that were shown to be involved in the oncogenesis of HCC cells are being pursued as potential novel therapeutic agents for the treatment of HCC. In addition to the potential of microRNAs as novel drug targets, microRNAs can also serve as diagnostic and prognostic biomarkers. Currently, diagnostics tests are crucial in the era of targeted therapies and the need for the identification of the right patient population that will benefit from a specific treatment. microRNA can be used for differential diagnosis, prognosis, early detection, companion diagnostic and drug monitoring. Rosetta Genomics is developing diagnostic tests that are directed to answer highly unmet medical needs in identifying tumor types and aid in choosing treatment modalities.
12:00-1:30 Lunch on your own
microRNA for Therapeutics
1:30-1:35 Chairperson’s Opening Remarks
Muthiah Manoharan, Ph.D., Vice President, Drug Discovery, Alnylam Pharmaceuticals, Inc.
1:35-2:00 Discovery of Antagomirs
Muthiah Manoharan, Ph.D., Vice President, Drug Discovery, Alnylam Pharmaceuticals, Inc.
Abstract unavailable at the time of printing.
2:00-2:25 Therapeutic Modulation of microRNAs
Juergen Soutschek, Ph.D., Senior Director, Scientific Development, Regulus Therapeutics
Abstract unavailable at the time of printing.
2:25-2:50 Targeting of Disease-Associated microRNAs with LNA-antimiRs
Morten Lindow, Ph.D., Group Leader, Bioinformatics, MicroRNA Research, 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 program and discuss different design options for potent LNA-antimiR compounds.
2:50-3:10 Networking Refreshment Break
3:10-3:35 Tumor Suppressor miRNAs: A New Therapeutic Opportunity
Andreas G. Bader, Ph.D., Senior Scientist, Mirna Therapeutics, Inc.
MicroRNAs (miRNAs) are small, naturally occurring molecules that regulate multiple genes and pathways that are critical in tumorigenesis and hence, can be exploited as drug targets in the intervention of cancer signaling. Expression profiling of human tumor samples, functional studies and pathway analyses has led to the identification of tumor suppressor miRNAs with broad activity in various cancer types and cancer models. We have validated the concept of “miRNA Replacement Therapy” which involves delivery of synthetic miRNAs into diseased tissues in an effort to reactivate pathways that drive a therapeutic response. Examples of miRNA therapeutics in mouse models will be discussed.
3:35-4:00 Development of Small Molecule Inhibitors of microRNAs
Qihong Huang, M.D., Ph.D., Assistant Professor, Systems Biology, Molecular and Cellular Oncogenesis Program, Wistar Institute
MicroRNAs (miRNAs) have recently emerged as an important class of gene regulators, and their misregulation has been linked to a variety of diseases. Small molecule inhibitors of miRNAs are important tools to elucidate the detailed mechanisms of miRNA function and provide lead structures for the development of new therapeutics. We developed a cell-based screen for miRNA pathway modifiers and identified the first small molecule inhibitors of oncogenic microRNA miR-21 function. This approach can be used for the development of suppressors or activators of microRNA functions that are involved in diseases.
4:00 Close of Conference