Cambridge Healthtech Institute’s Inaugural
Targeting Non-Coding RNA
The Long and the Short of It
March 5-7, 2012| Hilton San Diego Resort | San Diego, California

RNA has traditionally been thought of as a molecule that imparts information, structure or catalytic activities. The role of a subset of RNA known as non-coding RNA (ncRNA) – including small non-coding RNAs (siRNAs, piRNAs, and miRNAs) and long non-coding RNAs (lncRNA) – has increasingly come under scientific scrutiny. Recent progress suggests that the involvement of ncRNAs in human diseases could be far more prevalent than previously appreciated. Multiple lines of evidence increasingly link mutations and dysregulations of ncRNAs to diverse human diseases, ranging from neurodegeneration to cancer.

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MONDAY, MARCH 5

8:30 am Pre-Conference Short Course Registration


9:00 am-12:00 pm Recommended Pre-Conference Short Courses*

SC1: Epigenetics Toolbox

SC2: Sequencing 101

*Separate registration required.

12:00 - 2:00 pm Main Conference Registration

 

RNA: FROM TARGETS TO THERAPIES

2:00 Chairperson's Remarks

Jeff Falk, Ph.D., Director, Technical Services and Business Applications, Ribomed Biotechnologies, Inc. 


» 2:10 FEATURED SPEAKER:

Identification of Cellular Targets of Kaposi's Sarcoma-Associated Herpesvirus (KSHV) miRNAs by Ago HITS-CLIP

Rolf RenneRolf Renne, Ph.D., Professor, Molecular Genetics & Microbiology, University of Florida

KSHV is the etiological agent of Kaposi's Sarcoma, Primary Effusion Lymphoma and some types of Multicentric Castleman's disease. With the increasing evidence for the involvement of miRNAs in cancer, the fact that herpesviruses including KSHV and EBV express multiple miRNAs suggests a potential role for these miRNAs in viral tumorigenesis. Gene ontology analysis revealed that KSHV miRNAs directly regulate genes involved in cell cycle regulation, apoptosis, tumor suppression, immune evasion, and chromatin remodeling, suggesting a role in KSHV pathogenesis and potentially tumorigenesis.

2:45 RNAi as a Research and Therapeutic Tool: A Genome-Scale Lentiviral-RNAi Screen Identifies Novel Targets for Neratinib Sensitivity Leading to Neratinib and Paclitaxel Combination Drug Treatments

Attila Seyhan, Ph.D., Translational Immunology, Inflammation and Immunology, Pfizer, Inc.

I will discuss the identification of candidate genes that, when silenced, cause resistance to lethal concentrations of neratinib through a functional genetic screen.  To achieve this we used a pooled genome-wide lentiviral-shRNA library approach and microarray deconvolution and identified 128 novel chemoresistance genes that are involved in a variety of cellular functions. The identification of novel mediators of cellular resistance to neratinib, an experimental drug for cancer treatment, has profound implications for both basic and translational research.  It will greatly expand the knowledge on tumorigenesis and the mechanism of drug resistance in cancers dependent on ErbB2 signaling. It may also lead to the identification of novel targets and drug resistance markers.

3:20 Selected Poster Presentation: Silencing the Drugable Genome: Target Discovery Using Arrayed shRNA Adenoviral Libraries

André van Marle, Ph.D., Group Leader, Virus Production and Screening, Galapagos B.V.

3:35 Networking Refreshment Break

4:00 Developing Miravirsen:  Moving from the Lab to the Clinic

Bernard King, M.D., President and CEO, Macnas Consulting International; Senior Medical and Regulatory Consultant, Santaris Pharma AS

Miravirsen is the first microRNA-targeting agent to be administered to patients. Miravirsen is an LNA- modified phosphorothioate anti-sense oligonucleotide targeting and blocking liver-specific miR-122, a microRNA that is critical for hepatitis C virus (HCV) accumulation in the liver. In patients with HCV infection, miravirsen treatment is associated with prolonged dose-dependent anti-viral activity without evidence of viral resistance. Miravirsen has been safe and well tolerated with no dose-limiting toxicities. Miravirsen has the potential to eradicate chronic HCV infection as part of non-IFN regimens or as monotherapy. Further trials in all HCV genotypes, with longer duration of miravirsen therapy, alone and in combination with direct-acting antiviral agents, are planned.

4:35 The Discovery of Small Molecule miRNA Regulators for Therapeutic Applications

Douglas D. Young, Ph.D., Assistant Professor, Chemistry, College of William & Mary

The prevalence of miRNA misregulation in a variety of diseases and disorders suggests that they are prime targets for therapeutic intervention. Specifically, the development of high-throughput assays which target miRNAs represents a novel mechanism for the discovery of small molecule miRNA regulators that can be employed as cancer therapeutics. Utilizing this approach, small molecule activators and inhibitors of specific miRNAs have been discovered and their applications as therapeutic agents are currently being assessed.

 

» 5:10 FEATURED SPEAKER:

Deep Sequencing of Small RNAs from Human Skin Reveals Major Alterations in the Psoriasis miRNAome

Anne Bowcock, Ph.D., Professor, Genetics, Washington University School of Medicine

Psoriasis is a chronic and complex inflammatory skin disease with lesions displaying dramatically altered mRNA expression profiles, however, much less is known about the expression of small RNAs. We have performed a comprehensive analysis of the normal and psoriatic skin miRNAome with next-generation sequencing in a large patient cohort. Eighty known and 18 novel miRNAs were 2-42-fold differentially expressed in psoriatic skin. We also observed widespread expression of isomiRs and miRNA's derived from known and novel miRNA loci, and a low frequency of miRNA editing in normal and psoriatic skin. This study lays a critical framework for functional characterization of miRNAs in healthy and diseased skin.

5:45 Close of Day



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