Tuesday, March 29
7:30-8:15 am Breakfast Presentation (Sponsorship Opportunity Available) or
Morning Coffee
Contact Jon Stroup at jstroup@healthtech.com or 781-972-5483
microRNA and Cancer Stem Cells
8:25-8:30 Chairperson’s Opening Remarks
Jingfang Ju, Ph.D., Co-Director of Translational Research, Pathology, Stony Brook University
8:30-8:55 microRNA Gene Regulatory Pathways in Stem Cells and Cancer
Richard I. Gregory, Ph.D., Assistant Professor, Harvard Medical School, Harvard Stem Cell Institute, Children’s Hospital Boston
Post-transcriptional control of miRNA biogenesis has been observed in embryonic stem (ES) cells, embryonal carcinoma (EC) cells and primary tumors. These data support the notion that unidentified mechanisms exist in stem cells and certain cancers to prevent miRNA-mediated cell differentiation. We recently identified the developmentally regulated RNA-binding protein Lin28 as a selective inhibitor of the maturation of let-7 family miRNAs in embryonic cells. We seek to understand the mechanisms by which Lin28 controls miRNA biogenesis, as well as to identify novel miRNA regulatory pathways.
8:55-9:20 Implications of miRNAs in Colorectal Cancer and Cancer Stem Cells
Jingfang Ju, Ph.D., Co-Director of Translational Research, Pathology, Stony Brook University
We have recently developed a novel approach to discover both degraded and non-degraded miRNA mediated targets. We have discovered that several miRNAs (miR-140, miR-192, miR-215) played key roles in colorectal cancer by impacting cell proliferation, cell cycle control and chemoresistance. Some of the key targets (TS, DHFR, DTL, HDAC4) and pathways have been identified. The therapeutic potential and prognosis significance of these miRNAs were also investigated both in vitro and in vivo.
9:20-9:45 microRNAs: Native Regulators and Potential Therapeutics for Cancer Stem Cells
Liang Xu, M.D., Ph.D., Associate Professor, Department of Molecular Biosciences, University of Kansas
microRNAs have been implicated in cancer initiation and progression and are involved in cancer stem cell dysregulation. We show that CD44+/CD133+ cancer cells are enriched with cancer stem cells that have high levels of Notch/Bcl-2 and loss of miR-34. miR-34 restoration reduces the cancer stem cell population, inhibits tumorsphere growth and tumor-initiation in vivo via modulating Bcl-2 and Notch, supporting that miR-34 is involved in cancer stem cell self-renewal. Currently, we are exploring nanoparticle-targeted delivery of miR-34 to cancer stem cells as a novel molecular cancer therapy. Tumor targeted miRNA therapy holds promise as a novel molecular therapy targeting cancer stem cells.
9:45-10:45 Networking Coffee Break in the Exhibit Hall with Poster Viewing
Technology Showcase
Sponsored by
10:45-11:15 Discovery of a miRNA-Based RT-qPCR Signature Able to Detect Early Stage Colorectal Cancer in Blood Plasma
Adam Baker, Ph.D, Director, Diagnostics & Pharma Partnering, Exiqon A/S
Colorectal cancer (CRC) ranks 2nd in number of deaths among cancers of the western world. There is therefore a clear unmet need for a sensitive screening assay to select at-risk individuals for definitive diagnosis by colonoscopy.
To screen for miRNAs in blood plasma, we developed an LNA-enhanced miRNA RT-qPCR platform.
Using this platform, we performed a two-phased discovery program in plasma samples from stage II/III CRC patients and age- and gender-matched colonoscopy-verified healthy controls.
11:15 am-12:00 pm Panel Discussion: Potential of microRNA Biomarkers in Diagnostic Development
Moderator: Frank Slack, Ph.D., Professor, Department of Molecular, Cellular and Developmental Biology, Yale University
Panelists:
Adam Baker, Ph.D., Director, Diagnostics & Pharma Partnering, Exiqon A/S
Jingfang Ju, Ph.D., Co-Director of Translational Research, Pathology, Stony Brook University
Joanne Weidhaas, M.D., Ph.D., Assistant Professor, Therapeutic Radiology, Yale University School of Medicine
12:00-1:30 Lunch on Your Own
microRNA and Cancer Mechanism
1:30-1:35 Chairperson’s Opening Remarks
Rolf Renne, Ph.D., Professor, Department of Molecular Genetics and Microbiology, University of Florida
1:35-2:00 Causes and Consequences of microRNA Dysregulation in Cancer
Carlo M. Croce, M.D., Professor and Chair, Department of Molecular Virology, Immunology and Medical Genetics; Director, Institute of Genetics, Ohio State University
During the past several years it has become clear that alterations in the expression of microRNA genes contribute to the pathogenesis of most, perhaps all, human malignancies.These alterations can be caused by a variety of mechanisms, including deletions, amplifications or mutations involving microRNA loci, by epigenetic silencing or by dysregulation of transcription factors targeting specific microRNAs. Since malignant cells show dependence on the dysregulated expression of microRNA genes, which in turn control or are controlled by dysregulation of multiple protein coding oncogenes or tumor suppressor genes, these small RNAs provide important opportunities for development of future microRNA based therapies.
2:00-2:25 microRNA Regulation by Different Akt Isoforms
Philip Tsichlis, M.D., Jane F. Desforges Professor of Hematology and Oncology, Tufts Medical Center
2:25-2:50 microRNA Alterations that Contribute to Melanoma Metastasis
Eva Hernando, Ph.D., Assistant Professor, Department of Pathology, NYU School of Medicine
Recent evidence supports the contribution of altered microRNAs to melanoma progression. Using miRNA expression arrays, we identified miRNAs 30b and 30d (chr 8q24) as overexpressed in metastatic melanoma, with higher levels associated with increased stage. Ectopic expression of miR-30d enhanced melanoma cell invasion in vitro and metastasis in vivo. The analysis of potential downstream mediators revealed the involvement of adhesion molecules as well as of immune suppressive chemokines. Collectively, our results expand our understanding of the mechanisms that control melanoma metastasis, potentially revealing novel therapeutic avenues for patients for whom no viable approaches are currently available.
2:50-3:15 microRNAs and Prostate Cancer
Aurora Esquela-Kerscher, Ph.D., Assistant Professor, Department of Microbiology and Molecular Cell Biology, Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School
3:15-4:15 Networking Refreshment Break in the Exhibit Hall with Poster Viewing
4:15-4:40 microRNA Binding Site SNPs and Cancer Risk, Response and Outcome
Joanne Weidhaas, M.D., Ph.D., Assistant Professor, Department of Therapeutic Radiology, Yale University School of Medicine
It is well known that personal genetic variation is an important factor placing some individuals at a greater risk for developing cancer than the general population. To interpret how cancer-associated variations function, most published studies have focused on DNA alterations within protein-coding regions of genes from tumor tissue. However, our group has shown that cells (normal and/or tumor) from cancer patients also contain genetic variations with miRNAs and the 3'UTR (3'untranslated region) of cancer genes, and in some cases the variations specifically alter miRNA binding sites. We will present findings of 3'UTR's variants associated with cancer.
4:40-5:05 Functional Investigation of microRNAs Using Genomics and Proteomics
Jun S. Wei, Ph.D., Staff Scientist, Pediatric Oncology Branch, Oncogenomics Section, National Cancer Institute
microRNAs are an important class of gene expression regulators. This talk will give an overview of the important role of microRNA in human cancers. Studies of microRNA expression in pediatric malignancies using functional, genomic and proteomic approaches for clinical use such as diagnostic, prognostic biomarkers and as potential therapeutic targets will be discussed. New technologies such as next-generation sequencing to identify novel microRNAs in human cancers will also be introduced.
5:05-5:30 Discovery and Function of Tumor Virus microRNAs
Christopher S. Sullivan, Ph.D., Assistant Professor, Department of Molecular Genetics and Microbiology, The University of Texas at Austin
We, and others, have shown that human tumor viruses from the Polyoma and Herpes families encode microRNAs. While an understanding of the functions for most viral microRNAs remains incomplete, multiple studies have indicated that viral miRNAs will play an important role in down-regulating the expression of both host and viral-encoded genes. Here we present our efforts to identify new tumor virus-encoded miRNAs. We show that some of these newly-identified RNAs play a role in autoregulation of viral gene expression and may act via a mechanism that has so far escaped detection for virus-encoded transcripts.
5:30-5:55 Kaposi’s Sarcoma-Associated Herpesvirus miRNAs and their Roles in B Cell Development and Tumorgenesis
Rolf Renne, Ph.D., Professor, Department of Molecular Genetics and Microbiology, University of Florida
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent for KS and B-cell lymphomas, and expresses 17 miRNAs. To date, little is known about the roles that these miRNAs play in pathogenesis. One KSHV miRNA, miR-K12-11, shares 100% seed sequence homology with hsa-miR-155, an oncogenic miRNA that plays important roles in B-cell differentiation. Ectopic miRNA expression in human cord blood progenitors during hematopoiesis in NOD/LtSz-scid IL2Rγnull mice revealed that miR-K12-11 induces splenic B cell expansion and mimics miR-155. In addition, results from Ago-2/CLIP-Seq experiments performed in latently infected lymphoma cells will be discussed.