Epigenetics, microRNAs and non Coding RNAs in Disease Agenda

Registration

Technology Spotlight:
Gene Expression Analysis in Live Cells Using Novel RNA Detection Technology: SmartFlare™ RNA Detection Reagent
Goffredo Guarino, Technical Sales Scientist, Merck Millipore Bioscience

We present SmartFlare™ RNA Detection Reagent, a novel technology for detecting specific mRNA and miRNA in living cells. SmartFlare™ Probes enter cells via carrier free cellular uptake and are non-toxic, preserving the same cell samples for further downstream analysis.

Coffee and Networking in Exhibiton Hall

A Novel RNA Oligonucleotide Improves Liver Function and Inhibits Liver Carcinogenesis in vivo
Nagy Habib, Chief of Service/Professor, Imperial College London, United Kingdom

Hepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Therapies to simultaneously reduced tumour burden and improve liver function are limited. We designed short-activating RNAs (saRNA) to enhance expression of CCAAT/enhancer-binding protein-a (C/EBPa), a transcriptional regulator and activator of albumin gene expression. Intravenous injection of C/EBPa-saRNA in a cirrhotic rat model with multifocal liver tumours increased circulating serum albumin by over 30% showing evidence of improved liver function whilst tumour burden decreased by 80%.

Technology Spotlight:
microRNA Biomarkers in Biofluids: Challenges and Solutions
Ditte Andreasen, Scientific Manager, Exiqon A/S

microRNA profiling in biofluids is a promising, but also challenging source of new biomarkers for disease and toxicology. We will present how our solutions for sample and data qualification and analysis can ensure robust results in biomarker discovery and validation projects.

Lunch and Networking in Exhibition Hall

Poster Viewing Session

Therapeutic Delivery of mIRNAs to Inhibit Tumor Angiogenesis
Raymond Schiffelers, Professor of Nanomedicine, University Medical Center Utrecht, Netherlands

From a lentiviral screen of >1000 miRNAs, we identified several miRNAs with pronounced activity in in vitro angiogenesis assays. When inhibitory miRNAs were delivered to tumor tissue via local injection and electroporation or intravenous injection via an integrin-targeted nanoparticle we observed pronounced inhibition of tumor growth and angiogenesis. Aanalysis of the transcriptome after miRNA treatment revealed that several molecular targets for angiogenesis inhibtion were simulatenously regulated by a single miRNA species.

Human CD4+CD25+ Regulatory T Lymphocytes (Tregs): MicroRNA Expression Profile and Effect of Valproate Treatment on microRNA Signature and FOXP3 Expression in their Negative Counterparts (CD4+CD25- T Lymphocytes)
Hussein Fayyad-Kazan, Researcher, University of Brussels, Belgium

Regulatory T cells (Tregs) are a subpopulation of T cells with suppressive properties. We investigated human natural Tregs and identified a signature composed of five miRs. Using lentiviral transduction, we demonstrated that miR-31 and miR-21 had negative and positive effects on FOXP3 expression levels repectively. We thereafter showed that valproate treatment of human non-Tregs confers on them a molecular profile similar to that of their regulatory counterpart.

Coffee and Networking in Exhibiton Hall

RNA Therapeutics - The Silent Revolution
Dirk Haussecker, Consultant, RNAi Therapeutics Consulting, Germany

After some trial and error, RNA Therapeutics are now emerging as a major therapeutic platform.  While the explosion of genetic information is providing an abundance of targets, it is therapeutic RNA chemistry and delivery technologies that will determine how this revolution will unfold. This presentation will provide a sense of what is to come over the next 5 years.

Long Non-coding RNA in Cancer
Sven Diederichs, Group Leader/Principal Investigator, German Cancer Research Center, Germany

The majority of the human genome is transcribed into non- coding RNA. We investigate the role of long ncRNAs in cancer by profiling the expression of 17000 ncRNAs in three major tumor entities - lung, liver and breast cancer.In addition, we identified the lncRNA MALAT1 as a marker, active player and potential therapeutic target in lung cancer metastasis using a novel approach to create human knockout cells.

End of Day One

Cancer Epigenetics: Shaping the Tumor Methylome
Frank Lyko, Group Leader, German Cancer Research Center, Germany

Altered DNA methylation plays a major role in cancer development. This presentation will discuss the use of next-generation sequencing approaches for the characterization of mouse tumor models.

Coffee and Networking in Exhibiton Hall

Clinical Applications of DNA Methylation Markers: Promises and Pitfalls
Manon Engeland, Professor, Maastricht University, Netherlands

DNA methylation alterations are promising biomarkers for early detection of cancer and prediction of prognosis and response to anti-cancer therapy. Here I present the most promising methylation markers and the pitfalls associated with the implementation in clinical practice.

Epigenetic Variation as a Driver of Breast Cancer Risk
James Flanagan, Research Fellow, Imperial College London, United States of America

Many factors influence an individual’s risk of developing cancer, including genetic variation, lifestyle and environmental factors, such as alcohol intake and smoking. We hypothesise that epigenetic variation may be a driver of cancer risk whether by inherent constitutional variation or as a mediator of other factors.

Lunch and Networking in Exhibition Hall

Poster Viewing Session

Transcription Factors and DNA Methylation Changes in Cell Differentiation
Esteban Ballestar, Leader, The Bellvitge Institute for Biomedical Research, Spain

This presentation focuses on the role and mechanisms by which transcription factors participate in the acquisition of DNA methylation during differentiation in the hematopoietic system.

Shaping the Epigenome by Chromatin Dynamics
Fred van Leeuwen, Group Leader, Netherlands Cancer Institute, Netherlands

Histone modifications can be very dynamic. However, histones themselves can also be moved or replaced. Using  genetic screening and pulse chase methods we are determining the patterns and mechanisms of histone turnover and inheritance to determine how they influence the epigenome.

Coffee and Networking in Exhibiton Hall

Chromatin Mechanisms in Epigenetics
Luciano Di Croce, Group Leader, Center for Genomic Regulation, Spain

Polycomb group proteins have long been linked to the occurrence of different forms of cancer. Polycomb proteins form at least two distinct complexes: the Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2). Some of the PRC complex subunits have been found to be over-expressed in a variety of different tumors. Epigenetic perturbations are likely to be the cause for transcriptional misregulation of certain cell fates and of tumor suppressor genes. It is especially critical for stem cells that their potential to self-renewal and to differentiate is tightly controlled and properly orchestrated. Misregulation of Polycomb protein levels often leads to either a block or an unscheduled activation of developmental pathways, and thus to an enhanced capability to proliferate. The consequences of this misregulation have been linked to the establishment of cancer stem cells, which can produce tumors through the combination of an increase in self-renewal with a lack of complete cellular differentiation. Cancer stem cells are believed to persist within tumors and to elicit relapse and metastasis. I will discuss how Polycomb proteins impact on cancer, and their role in stem cell biology.

Close of Conference