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Wednesday, March 26

7:00am Registration (Open until 5:30pm)

8:00 Plenary Keynote Introduction
Edward G. Heidig, General Counsel and Deputy Secretary, Business, Transportation and Housing Agency

8:10 Risk Diagnosis for Disease Prevention
C. Thomas Caskey, M.D., F.A.C.P., Director and Chief Executive Officer, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center 
There are an increasing number of presymtomatic diagnostic options which 
include: genetic, imaging, and analyte technology. Examples of linking a specific diagnostic to a therapeutic decision and FDA approval have fueled the activity for personalized medicine. It must be appreciated that diagnostic capacity emerges far more rapidly than an approved safe therapeutic. Thus the personalized medicine goal has a bottle neck for broad utility. A strategy of studying approved drugs for maximal efficacy is realistic and reasonable toward that goal since it is estimated that many approved drugs are effective in less than 50% of patients. These approaches will be discussed.

8:55 Disruption of the Pharmaceutical Industry: Moving from Products to Solutions
Theodore J. Torphy, Ph.D., Corporate Vice President & Head, Science & Technology, Johnson & Johnson
The pharmaceutical industry is bracing itself for a period of unprecedented challenges. This new era for our industry is being brought on by the confluence of several environmental factors, both internal and external to the industry, including; 1) non-sustainable increases in healthcare expenditures, 2) spiraling costs and decreasing productivity of R&D, 3) reimbursement driven by medical and economic outcomes, and 4) the proliferation and redistribution of healthcare outcomes information. Although all of these factors threaten to disrupt our industry, it is the evolving transparency in healthcare outcomes information that represents the most unsettling threat to our current business model, as well as the largest opportunity to transform our industry. For this transformation to take place, it is imperative that we change from an industry in which the sole mission is to provide products to one that provides broader, cost-effective solutions to areas of major healthcare needs.

9:40 Grand Opening Refreshment Break in the Exhibit Hall

11:00 Chairperson's Remarks
Dalia Cohen, Ph.D., Executive Vice President, Head, Research and Development, Rosetta Genomics

11:10 microRNA Regulation in Normal and Neoplastic Mature B-Cells
Andrea Califano, Ph.D., Professor and Director, Genome Center Bioinformatics, Columbia University 
In order to further our understanding of the interplay between microRNA (miRNAs) and cellular networks in mature B cell function and lymphomagenesis, we analyzed the miRNA and mRNA expression profile of B cells at different stages of differentiation by cloning short RNA and by array-based miRNA expression studies. We generated libraries representative of miRNAs expressed in normal germinal center (GC), na・e and memory B cells isolated from human tonsils and in a Burkitt lymphoma cell line (Ramos). These were sequenced to identify short RNAs, which were further processed computationally to identify flanking regions whose folding characteristics would be consistent with a precursor miR structure. The analysis identified 201 mature miRNA that were cloned from normal B cells and Ramos cell line and were computationally validated. Comparison with current miRNA database (miRBase v10.0) showed that 109/201 miRNAs were previously reported. Overall, this analysis led to the discovery of 92 not previously reported miRNAs, several of which were confirmed by Northern assays, and allowed us to identify the complete miRNA expression profile of B cells at different stages of development. This data shows that there is still an abundance of tissue and tumor specific miRs that are yet to be discovered and functionally classified. 

11:40 A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing
Pablo Landgraf, M.D., Ph.D. Group Leader, Department of Pediatric Oncology, Hematology and Clinical Immunology, Children's Hospital of the Heinrich-Heine University D・seldorf
microRNAs (miRNAs) are small noncoding RNAs that reduce stability and/or translation of fully or partially sequence-complementary target mRNAs. In order to identify the pre-dominantly present miRNA sequence, investigate miRNA expression patterns and modifications we cloned and sequenced over 260 small RNA libraries from 26 different organ systems and cell types of human and rodents with emphasis on the hematopoietic and neuronal system. I will present results from this study giving account for the numbers of miRNAs present in mammalian cells, the degree of editing and outlining that, astonishingly, a fairly small set of miRNAs, most of them ubiquitously expressed, account for most differences between different lineages in hematopoiesis.

12:10pm A Role for microRNA Alterations in Melanoma Progression
Eva M. Hernando, Ph.D., B.S., Assistant Professor, Pathology, New York University
We have found consistently altered in metastatic melanoma cell lines the expression of miRNAs located in the 7q locus, which is frequently amplified in melanoma and contains the B-RAF oncogene. Moreover, stable transduction of mela-noma cell lines with specific miRNAs was able to significantly enhance their in vitro oncogenic potential and in vivo metastatic behavior. Overall, our data revealed a novel role for microRNAs in melanoma progression. Direct targets of these miRNAs are currently been analyzed in order to understand the mechanism by which they promote melanoma aggressiveness. Finally, evaluation of miRNA levels in human specimens is also underway to determine the value of these miRNAs as prognostic biomarkers.

12:40 Technology Spotlight Emerging Technologies for RNAi-based High-throughput Genomic Research

Sponsored by Thermo Scientific

Thomas J. Murphy, Ph.D.m Field Applications Scientist, Research and Development, Thermo Fisher Scientific, Dharmacon Products Gene silencing by small interfering RNA (siRNA) has emerged as a critical technology to assess biological function. However, delivery and functionality in hard-to-transfect cells remains a challenge. We have developed innovative technologies for delivery in lipid-independent scenarios. The integration of these emerging technologies with high-throughput screening accelerates drug discovery programs.

1:10 Walk & Talk Luncheon in the Exhibit Hall

2:15 Chairperson's Remarks
Tara M. Love, Ph.D., Cancer Immunology and AIDS, Dana-Farber Cancer Institute 

 

2:20 Non Coding RNAs Involvement in Cancer Predisposition and Tumor Development George A. Calin, M.D., Ph.D., Associate Professor, Department of Experimental Therapeutics, University of Texas, MD Anderson Cancer Centre  microRNAs were linked to the progression of all types of human tumors that  were investigated to date. The main molecular alterations are represented by variations in gene expression, usually mild and with consequences for a vast number of target protein coding genes. Recent studies proved that miRNAs are main candidates for the elusive class of cancer predisposing genes and that other types of non-coding RNAs participate in the genetic puzzle giving rise to the malignant phenotype. These discoveries could be exploited for the development of useful markers for diagnosis and prognosis, as well as for the development of new RNA-based cancer therapies.

2:50 Therapeutic Potential of Targeting microRNAs in Chronic Myeloid Leukemia 
Tara M. Love, Ph.D. 
microRNAs (miRs) are small, endogenous, non-coding RNAs that silence largenumbers of genes and are also useful in the sensitive classification of cancers. We discovered a complement of miRs whose expression is differentially regulated in normal lymphoid versus myeloid development. Several of these miRs are also differentially expressed in lymphoid versus myeloid blast phases of chronic myeloid leukemia (CML), suggesting that the natural function of these miRs is dysregulated in CML. This talk will outline evidence that modulation of specific miR activities in CML cells affects the transition to blast phase and/or lineage determination in blast phase, thus laying the foundation for therapeutic silencing by miRs and antagomiRs in CML.

3:20 Evidence of a More Pronounced Role for Animal microRNA Activity
Isidore Rigoutsos, Ph.D., Manager, Bioinformatics & Pattern Discovery Group, Computational Biology Center, IBM Thomas J. Watson Research Center 
microRNAs are short RNAs that have been shown to either direct mRNA degradation or disrupt mRNA translation in a sequence-dependent manner. Studies so far on naturally occurring binding sites have supported a model by which animal microRNAs act through the 3・untranslated regions of targeted transcripts. In this talk, I will present results from our recent studies with a number of different microRNAs and biologically significant transcripts. Our work provides evidence that, in addition to 3旦TRs, animal mi-croRNAs can also target extensively sites which occur naturally in the 5旦TRs and the CDSs of transcripts, and that disruption of these interactions can lead to significant, meas-urable changes in specific cell types.

3:50 microRNA Pathway and Human Diseases
Peng Jin, Ph.D., Department of Human Genetics, Emory University 
Small RNAs (18-28nt), including microRNAs (miRNAs), have been increasingly recognized to play critical roles in many forms of gene regulation and diverse cellular pathways, including stem cell maintenance and differentiation. Although major components in the RNAi pathway have been identified, regulatory mechanisms for this pathway remain largely unknown. In my presentation, I will discuss our most recent work on understanding the role of microRNA pathway in different inherited disorders and how the misregulation could contribute to disease pathogenesis.

4:20 Reception in the Exhibit Hall (Sponsorship Available)

5:00 - 6:00pm Break-out Discussions in the Exhibit Hall