GeneExpression Systems of USA and University of Cambridge of UK
Appasani Research Conferences (ARCEI.ORG)
Jointly Presents
Fifth International

MicroRNAs Europe 2010 Meeting

on
MicroRNAs: Biology to Development and Disease

November 1 - 2, 2010
Venue: Peterhouse, University of Cambridge, Cambridge, UK

A Unique Theme Conference & Exhibition in the MicroRNomics!

Meeting Place:

The Venue Peterhouse (middle) is the oldest College of the University of Cambridge, founded in 1284 and an institution dedicated to education and research. Throughout its history, Petreans have been at the heart of the political, social and religious controversies that have shaped today’s society. Some of the influential Petreans include: Henry Cavendish, Lord Kelvin, Sir Frank Whittle and Christopher Cockerill, and Nobel Laureates – Sir John Kendrew, Sir Aaron Klug, Archer Martin and Max Perutz , who gave a twentieth century lead in the field of Molecular Biology. Since many centuries it remained as a hub for innovation and successive generations of the brightest young people around the world.

Why do you wait to join for an intellectual gathering in the ‘microRNomics’ arena at the prestigious college Peterhouse in the Premier University campus!

(click here for meeting poster)

AGENDA/SPEAKERS

Monday, November 1, 2010

7:00 – 8:30 A.M: Registration Open
7:30 – 8:45 A.M: Continental breakfast
8:00 - 9:30 A.M: Technology Session I (consists of 3 lectures)

Tuesday, November 2, 2010

7:00 – 8:30 A.M: Registration Open
7:30 – 8:45 A.M: Continental breakfast

8:00 - 9:30 A.M: Technology Session II (consists of 3 lectures)
Scientific Sessions Start at 9:30 A.M and Ends at 6.00 P.M on all two days.

Organizers:

Krishnarao Appasani, PhD., MBA (Chair)
Founder & CEO
GeneExpression Systems, Inc. Waltham, MA USA

Sakari Kauppinen, Ph.D.
Associate Director
Santaris Pharma, Copenhagen, Denmark

Anton J. Enright, PhD.
Group Leader at European Bioinformatics Institute
Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom

Eric A. Miska, PhD.
Assistant Professor at the Wellcome Trust/Cancer Research UK/Gurdon Institute
University of Cambridge, Cambridge, United Kingdom


Keynote Speakers:

	Chris Boshoff, MD, PhD, MRCP            Professor & Director of Cancer Institute University College of London London, United Kingdom Title: Kaposi sarcoma: the role of viral and cellular miRNAs
	Arthur A. Levin, PhD. Industry Keynote Speaker Vice President & Chief Development Officer Sataris Pharma, US Operations San Diego, CA, USA Title: Non-clinical and clinical development of miravirsen, a microRNA-122 inhibitor

Other Speakers:

	Pavel Sumazin, Ph.D. Research Scientist Sulzberger Columbia Genome Center Columbia University, New York, NY, USA Title: Glioblastoma-related microRNA regulators and targets
	Anton J. Enright, PhD, Group Leader European Bioinformatics Institute Wellcome Trust Genome Campus, Hinxton, Cambridge, UK Title: Detection of microRNA binding and siRNA off-targets from expression data
	Marketing Manager Febit biomed, GmbH, Germany Title:miRNA biomarker profiling from blood – A promising approach for non-invasive diagnostic testing
	Laura Pazzaglia, PhD.                                  Laboratory of Experimental Oncology                        Itituto Ortopedico Rizzoli Bologna, Italy Title: miRNAs in Osteosarcoma
	Vincent O'Brien, PhD.                      Chief Scientific Officer Sistemic UK Glasgow, Scotland, United Kingdom Title: TBA
	Angelika Bonauer, PhD.                              Inst for Cardiovascular Regeneration Center for Molecular Medicine Goethe University of Frankfurt Frankfurt, Germany Title: miRNA-92 in ischemic recovery
	Dr. Mikhail Klenov                                        Institute of Molecular Genetics Russian Academy of Sciences Moscow, Russia Title: piRNA-mediated gene silencing
	Ykä (Yrjö) Helariutta, PhD. Professor of Botany & Plant Molecular Biology University of Helsinki-Institute of Biotechnology Helsinki, Finland Title: Cell signaling by miR-165/166 in plant pattern and organ development
	Cindy Horwedel                                            Graduate Student in the Lab. Of Dr. Ulrich Tschulena Division of Molecular Genome Analysis Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Germany Title:A novel large-scale screen to identify modulators of oncomir miR-21
	Matthew J.A. Wood, BM BCh., DPhil.         Lecturer in Biomedical Science University of Oxford Oxford, UK Title: Non coding RNAs in neurodegenerative diseases
	Alain Sewer, PhD.                                         Scientist - Disease Modeling & Simulation                 Phillip Morris International R&D Neuchatel, Switzerland Title: novel miRNA normalization methods
	Beate Niesler, PhD.                                     Scientist & Group Leader Institute of Human Genetics, University of Heidelberg Heidelberg, Germany Title: TBA
	Kyriacos N. Felekkis, PhD.                          Scientist in the Biological Sciences University of Cyprus Nicosia, Cyprus Title: TBA
	Michael J. Kerin, MCh., FRCSI.                  Professor and Head of Surgery National University of Ireland, School of Medicine & University Hospital, Galway, Ireland Title: microRNAs in breast cancer
	Pieter Mestdagh                                           Ph.D Student in the Center for Medical Genetics Ghent University Hospital, Ghent, Belgium Title: The microRNA body map: dissecting microRNA function through integrative genomics
	Maria Roubelakis, DPhil.                             Cell and Gene Therapy Laboratory                             Biomedical Research Foundation, Academy of Athens Athens, Greece Title: Identification and functional analysis of miRNAs expressed in human mesenchymal stem cells
	Francesca Ruberti, PhD.                             CNR-Institute of Neurobiology and Molecular Medicine Roma, Italy Title: microRNAs in neurodegenerative diseases
	Kenneth Lonvik PhD Student                                                   University of Northern Norway Title: Prognostic Impact of miRNAs in NSCLC Evaluated by High Throughput in Situ Hybridization and LNA Microarrays
	Nan Shen, MD.                                              Professor of Medicine &Director Shanghai Institute of Rheumatology Renji Hospital, JiaoTong University, Shanghai, China Title: microRNAs in autoimmune diseases, mainly on human lupus
	Iris Lavon PhD.                                             Professor & Head of Molecular Neuro-Oncology Hadassah Hebrew University Medical Center Jerusalem, Israel Title: Do microRNA clusters that share reminiscent expression profile between glioma and neural precursor cells have a role in tumorigenesis
	Muhammad I. Aslam, PhD.               Scientist in the Molecular Medicine University of Leicester & Leicester Royal Infirmary Leicester, UK Title: MicroRNAs are novel biomarkers of colorectal cancer
	Sakari Kauppinen, PhD. Director Santaris Pharma, Horshol, Denmark Title: Targeting of microRNAs for therapeutics
	Nagy Habib, MB Ch., PhD., FRCS.             Professor of Surgery & Director of HPB Services Imperial College London & Hammersmith Hospital, London, UK Title: Characterization of short RNAs that activate KLF4 expression
	Bassam Badran, PhD.                                  Professor of immunology Dept of Biochemistry                        Lebanese University, Faculty of Sciences Hadath Beirut, Lebanon Title: Valproate treatment of CD4+CD25- T cells transiently confers on them a Treg microRNA profile

Key Sessions:

The most-up-to-date developments will be addressed:
MicroRNAs Discovery and Biogenesis
MicroRNAs in Development
Bioinformatics of miRNAs
MicroRNAs in Virology & Diagnostics
MicroRNAs in Stem Cell Biology
MicroRNAs in Disease Biology

Exhibitors are welcome to reserve their booth space early!

Please contact if you are interested in speaking in the scientific or Technology workshops of this meeting.

GeneExpression Systems, Inc.
P.O. Box 540170
Waltham, MA 02454 USA
Tel: (781) 891-8181
Fax: (781) 891-8234
E-mail: Genexpsys@expressgenes.com
www.expressgenes.com

Poster Abstract Submission by October 1, 2010

Abstracts

MiRNAs   in Osteosarcoma
Laura Pazzaglia1, Chiara Novello1, Amalia Conti1, Irene Quattrini1, Luisa Montanini2, Piero Picci1 and Maria Serena Benassi1
1Laboratory of Experimental Oncology,  Istituti Ortopedici Rizzoli, Bologna – Italy
2Center for Molecular and Translational Oncology, University of Parma - Italy

Abstract: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults. Conventional therapy for OS has reached a plateau of 60-70%, a 5-year survival rate that has changed little in two decades, highlighting the need for new therapeutic approaches by the research  of new targets. We performed different  high-throughput analysis on OS cell lines and samples and we have identified  several differentially expressed  miRNA (in particular mir-196a, mir-1, mir-133b).
In vitro functional studies are on-going  to better investigate  the role of these miRNAs as potential prognostic marker and drug target.

 The microRNA body map: dissecting microRNA function through integrative genomics
Pieter Mestdagh1*, Steve Lefever1*, Filip Pattyn1,2, Dana Ridzon3,  Annelies Fieuw1, Joëlle Vermeulen1, Anne De Paepe1, Linda Wong3,  Frank Speleman1, Caifu Chen3, Jo Vandesompele1
1Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium. 2German Cancer Research Center (DKFZ), Heidelberg, Germany. 3Life Technologies, Foster City, California, USA. *Equally contributing authors

Abstract: MicroRNAs are tiny regulators of coding gene expression. While a growing body of evidence implicates deregulated microRNA expression in various aspects of human disease, including cancer, insights in global microRNA function remain limited. Here, we present the microRNA body map, an interactive online compendium and mining tool of high-dimensional newly generated and published microRNA expression profiles along with functional annotation inferred through integrative transcriptomics. The microRNA body map enables prioritization of candidate microRNAs based on their expression profile across tissue or disease subgroup and based on a new functional annotation. The microRNA body map project has great potential to become a community resource.

Anovellarge-scale screen to indentify modulators of oncomir miR-21
Horwedel C, Keklikoglou I, Zhang J, Diederichs S, Wiemann S, Tschulena U

Division Molecular Genome Analysis, DKFZ (German Cancer Research Center), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany

Abstract: MicroRNA-21 is upregulated in different cancers and modulates cancer-relevant processes. To identify genes involved in the regulation of miR-21, we have screened a large-scale siRNA-library. We have identified 100 genes that significantly regulate miR-21 activity. These candidates were followed up in different assays to analyze whether these genes function at the transcriptional or post-transcriptional level. Moreover, these genes were also analyzed for their ability to modulate other microRNAs to identify general regulators of miRNA biogenesis. Individual candidates are currently analyzed for their specific mode of miR-21-activity modulation. Thus, by these screens we identified miR-21 specific and general regulators of miR-processing.

Do microRNA Clusters That Share Reminiscent Expression Profile Between Glioma and Neural Precursor Cells Have a Role in Tumorigenesis?
Iris Lavon1,2, Daniel Zrihan1,2, Avital Granit1,2, Ofira Einstein2, Yoav Smith3,
Tamir Ben-Hur2 and Tali Siegal1.
1Gaffin Center for Neuro-Oncology, 2Department of Neurology, 3Genomic Data Analysis Unit, Hadassah Hebrew University Medical Center

Abstract: We showed that gliomas exhibit a miRNA expression profile reminiscent of neural precursor cells. About half of the miRNAs expressed in the shared profile, cluster in seven genomic regions susceptible to genetic/epigenetic alterations in cancers. Our study provided the first evidence for association between these clusters and gliomas. Some of these clusters such as mir17-92 were reported to have a pro-oncogenic role, while the potential tumorigenic role of clusters, such as the 53 miRNAs cluster on chromosome 14q32.31, remains unknown. Our current study which aims to reveal the tumorigenic role of the cluster on chromosome 14q32.31 and previous results will be discussed.

Identification and functional analysis of miRNAs expressed in human mesenchymal stem cells
Maria Roubelakis, DPhil., Cell and Gene Therapy Laboratory, Foundation for Biomedical Research of the Academy of Athens, Athens, Greece;

M.G. Roubelakis1,2 , O. Trohatou1,2,  D. Zagoura1,2,  P. Zotos1,3, V. Bitsika1,2, S. Kossida3, Κ.Ι. Pappa1,2,4 , A. Antsaklis4 and N.P. Anagnou1,2

1Cell and Gene Therapy Laboratory, Foundation for Biomedical Research of the Academy of Athens, Athens, Greece; 2Laboratory of Biology, University of Athens School of Medicine, Athens, Greece; 3Bioinformatics Department, Foundation for Biomedical Research of the Academy of Athens, Athens, Greece; 4Department of Obstetrics and Gynecology, University of Athens School of Medicine, Athens, Greece.

Abstract: Human mesenchymal stem cells (hMSCs) represent a population of multipotent stem cells, easily expanded in culture and able to differentiate into many lineages. Our group has isolated MSCs the amniotic fluid (AF). To further decipher the molecular mechanisms as they relate to the MSCs from bone marrow (BM) and umbilical cord blood (UCB), we investigated the comparative post-transcriptional regulation mechanisms of MSCs from the three sources at the miRNA level. More specifically, the objectives of the study were i) the detection of miRNA populations in AF, BM and UCB-MSCs, ii) the validation of their expression levels using Real Time PCR, iii) the generation of a new algorithm for the in silico detection of miRNA target-genes, iv) the validation of miRNA binding on specific targets predicted by the algorithm application and v) the determination of specific miRNA funcrional role.

Valproate treatment of CD4+CD25- T cells transiently confers on them a Treg microRNA profile
Badran Bassam, PhD., Professor of Immunology, Department of Biochemistry, Laboratory of Immunology, Faculty of Sciences; EDST-PRASE, Lebanese University, Hadath Beirut, Lebanon

Fayyad-Kazan Hussein1†, Rouas Redouane1†, Zeineddine Ibrahim2, Makhour Yolla2, Hamade Eva2, Badran Rabih1, Fayyad-Kazan Mohammad1, Lewalle Philippe1, Jebbawi Fadi1, Romero Pedro3, Burny Arsène1, Martiat Philippe*1 and Badran Bassam*2. 

1. Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de
Bruxelles, 121, Boulevard de Waterloo, 1000, Bruxelles, Belgium
2. Department of Biochemistry, Laboratory of Immunology, Faculty of Sciences; EDST-
PRASE, Lebanese University, Hadath Beirut, Lebanon.
3. Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne
branch, 4 Av. Pierre-Decker, 1005 Lausanne, Switzerland

Abstract: Regulatory T-cells (Tregs) play a key role in immune system homeostasis and tolerance to antigens, thereby preventing autoimmunity, and may be partly responsible for the lack of an appropriate immune response against tumor cells. Although not sufficient, a high expression of FOXP3 is necessary for their suppressive function. Recent reports have shown that HDAC inhibitors (SAHA) modulated microRNA expression profiles in various cell types. We therefore decided to investigate the effect of valproate on microRNA expression profile in CD4+CD25- T cells purified from cord blood. We found that, valproate treatment induced the acquisition of the miRs Tregs signature. To elucidate whether the changes in the miRs expression could be due to the increased FOXP3 expression, we transduced these non-Tregs with a FOXP3 lentiviral expression vector, and found no changes in miRs expression. Therefore the modification in their miRs expression profile is not due to an increased expression of FOXP3, but directly results from HDAC inhibition.
We conclude that valproate treatment of human non-Tregs confers them a microRNA profile similar to that of their regulatory counterpart.

Prognostic Impact of miRNAs in NSCLC Evaluated by High Throughput in Situ Hybridization and LNA Microarrays
 Kenneth Lonvik, PhD Student, Dept of Clinical Pathology, The University Hospital of
Northern Norway, Tromsoe, Norway

Abstract: For the past two years, our research group has investigated the prognostic impact of different miRNAs in Non-Small Cell Lung Cancer (NSCLC), by in situ hybridization (ISH) and LNA microRNA microarray analysis. We have previously published several papers on expression of proteins and their receptors in NSCLC. We have a biobank containing tumor specimens from 335 patients diagnosed with NSCLC stage I – IIIA. From these specimens we have made TMAs (Tissue MicroArrays), making it possible to analyse many patients simultaneously by in situ hybridization. For LNA microarrays we selected ten patients with high survival, ten with low survival and ten normal lung tissue samples. By LNA microarray we found more than 60 microRNAs to be differently expressed in lung tumors compared to normal lung tissue (p < 0.012, FDR < 0.1). We also found significant differences between patients with long and short postoperative survival. More than 30 microRNAs were differently expressed between these two groups (p < 0.02, FDR < 0.33). We have so far performed ISH on two different miRNAs; has-miR-155 and has-miR-126. We found miR-155 to have some prognostic impact in NSCLC, depending on histological subtype and nodal status. miR-126 expression was shown to have a significant impact on disease-specific survival, where high expression was linked to a poorer prognosis than low expression. The results have been verified by qRT-PCR

Characterization of short RNAs that activate KLF4 expression
Nagy Habib, MB Ch., PhD., FRCS., Professor of Surgery & Director of HPB Services, Faculty of Medicine-Imperial College London & Hammersmith Hospital, London, UK

Pål Sætrom1,2,3, John J. Rossi4, Noriyuki Kasahara5, Jessica Alluin4, Paul Mintz6,  Nagy A. Habib6
1Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NO-7489 Trondheim, Norway
2Department of Computer and Information Science, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway
3Interagon AS, Laboratoriesenteret, NO-7489 Trondheim, Norway
4Division of Molecular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
5Department of Medicine, UCLA School of Medicine, 675 Charles E. Young Drive South, MRL-1551, Los Angeles, CA 90095-7019
6Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK

It is well recognized that short interfering RNA (siRNA) sequences play an important role in gene expression. These are a class of short double-stranded RNA molecules involved in the RNA interference (RNAi) pathway, which regulates the expression of specific genes. In recent years, siRNA sequences have been exploited to study the molecular and biological properties of stem cells primarily by down-regulating specific genes. We have taken a novel genomic-bioinformatic approach to design short activating RNA (saRNA) molecules that can up-regulate specific genes. We show proof-of-principle that saRNAs could be designed to up-regulate specific genes such as Kruppel-like factor 4 (KLF4). The KLF4 gene is a transcription factor necessary for maintaining embryonic and somatic stem cells that control the expression of pluripotency genes including POU5F1, Sox2, c-Myc, and Nanog. We have designed and tested several saRNAs to up-regulate the KLF4 gene. We demonstrate that some of the saRNAs can up-regulate KLF4 in addition to Sox2, c-Myc, and Nanog expressions in hematopoietic and mesenchymal stem cells. The genomic-bioinformatic method of identifying saRNAs for the study of stem cell properties could have broad implications in stem cell research.

Glioblastoma-related microRNA regulators and targets
Pavel Sumazin, Ph.D., Research Scientist & Associate Director for Bioinformatics
Sulzberger Columbia Genome Center, Columbia University, New York, NY, USA

Pavel Sumazin, Wei-Jen Chung, Hua-Sheng Chiu, Xuerui Yang, Mukesh Bansal, Andrea Califano

Recent evidence suggests that MicroRNAs (miRs), including MiR-26a, miR-221/2 and a battery of differentially expressed miRs across tumors and prognosis may be key regulators of Glioblastoma multiforme (GBM) tumorigenesis. To characterize their regulatory role, we constructed an integrated gene-miR regulatory network that is being used to identify GBM master regulators. We will present our work on identifying miR regulators and targets in GBM tumors. We will present models, algorithms, and results from validation experiments, including validated predictions of post transcriptional regulators of miR biogenesis, modulators of miR regulation, and synergistic miR targeting.

MicroRNAs in neurodegenerative diseases
Francesca Ruberti, PhD., CNR-Institute of Neurobiology and Molecular Medicine
European Brain Research Institute, Rome-Italy

Francesca Ruberti 1, Elisa Vilardo1, Christian Barbato1 Maria Teresa Ciotti1, Carlo Cogoni2
INMM-Istituto di Neurobiologia e Medicina Molecolare, CNR, Rome-Italy
EBRI-European Brain Research Institute, Rome-Italy