March 17, 2014, 9:00 am-12:00 pm
SC1: Long Non-Coding RNAs as Biomarkers
Non-Coding RNA and DNA Utility as Biomarkers in Tissue and Blood
Dave S.B. Hoon, Ph.D., Director, Molecular Oncology, John Wayne Cancer Institute
As we have decoded the human genome in more depth with next-generation sequencing, multiple new short and long non-coding RNA have been identified. Short non-coding RNA have been shown to have significant functional activity in cancer development and progression thus also can be utilized as cancer biomarkers in both tissues and body fluids. The long non-coding RNA field has only recently started to develop rapidly; however, their functional activity still is poorly understood. Long non-coding RNA has recently been shown to have potential as tissue biomarkers. Assessment of long non-coding RNA in robust assays still remains to be developed technically whereby, short non-coding RNA is relatively easy to detect as biomarkers and functional activity.
LncRNAs and miRNAs as Biomarkers and Therapeutic Targets in Cancer
Jingfang Ju, Ph.D., Associate Professor, Co-Director, Translational Research, Pathology, Stony Brook University
Over 97% of the human genome is non-coding DNA. With the discovery and functional studies of highly conserved non-coding RNAs in recent years, we now appreciate the impact of non-coding RNAs in diseases such as cancer. We have discovered a number of miRNAs that impact cell cycle, apoptosis, EMT transition, autophagy, and proliferation in colon cancer and endometrial cancer. More importantly, a number of them impact chemoresistance in cancer stem cells and are significantly associated with prognosis.
Regulation of Red Blood Cell Differentiation by Long Non-Coding RNAs
Wenqian Hu, Ph.D., Senior Research Associate, Lodish Lab, Whitehead Institute for Biomedical Research, MIT
Genomic studies have identified thousands of long non-coding RNAs (lncRNAs) in the mammalian genome that are differentially expressed during development and pathogenesis. Here we use red blood cell differentiation as a system to illustrate how to identify lncRNAs from transcriptomic datasets and functionally characterize these RNA transcripts.
Investigating the Role of Long Non-Coding RNA in Innate Immunity
Susan Carpenter, Ph.D., Postdoctoral Scholar, McManus Lab, University of California San Francisco
An inducible program of inflammatory gene expression is central to anti-microbial defenses. We have identified a group of ‘immune regulated’ large intervening non-coding RNAs (lncRNAs) that are upregulated during the inflammatory response. The highly upregulated lincRNA-Cox2 is a key regulator of this response, where it acts to transcriptionally repress interferon stimulated genes (Ccl5) and promote pro-inflammatory cytokines (Il-6). Further understanding of lincRNA function in innate immunity may reveal novel drug targets and biomarkers for infectious and inflammatory diseases.
March 17, 2014, 6:00-9:00 pm
SC2: Exosomal microRNAs as Non-Invasive Biomarkers
Circulating Exosomal RNA as Diagnostic Markers and Real-Time Therapeutic Markers for Cancer
Douglas D. Taylor, Ph.D., Professor, Obstetrics, Gynecology, and Women’s Health, University of Louisville School of Medicine
Recent studies have examined the diagnostic utility of profiling total circulating miRNA in cancer patients; however, no study, to date, has defined circulating RNA signatures derived specifically from the tumor. Since there is a significant exosome contribution from inflammatory cells, platelets, and vascular endothelial cells, this general profiling approach exhibits a large noise-to-signal ratio. To address this need, we have developed the methodology to isolate and profile RNA specifically associated with exosomes derived from the tumor as diagnostic markers and to further correlate the differential expression of specific miRNA with clinipathologic data to identify miRNA populations defining prognosis, primarily recurrence.
Clinical Utilization of Exosome-Associated miRNA
Cicek Gercel-Taylor, Ph.D., Clinical Research Director, Exosome Sciences
Technology Assessment for Evaluation of microRNAs as Novel Biomarkers
Shidong Jia, Ph.D., Scientist, Genentech
Speaker biography: Dr. Shidong Jia is a scientist at Genentech, Inc., where he leads biomarker development efforts in support of Genentech's oncology pipeline and companion diagnostic co-development in clinical trials. His lab conducts disease-focused translational research and develops innovative cutting-edge technologies that have the potential to enable advanced biomarker studies in the clinic. Prior to joining Genentech, Dr. Jia was Lab Head of Oncology Drug Discovery at the Novartis Institutes for BioMedical Research in Cambridge, MA. Dr. Jia was recognized among the first to identify p110beta as a novel drug target for PTEN-deficient tumors (Nature, 2008), a finding that helped to lay the foundation for clinical testing of p110beta inhibitors in cancer. Dr. Jia serves as co-Editor-in-Chief of the journal Exosomes and Microvesicles and is a recipient of several awards, including the "Young Investigator Award" at the Fourth Asian Congress for Microcirculation and the "P.A.R.T. Investigatorship Award" at the Dana-Farber Cancer Institute, Harvard Medical School.
Circulating Exosomes in Liver Disease
Gyongyi Szabo, M.D., Ph.D., Professor and Vice Chair, Research, Department of Medicine, University of Massachusetts Medical School
microRNAs (miRNAs) are fine tuners of diverse biological responses and are expressed in various cell types of the liver. They can also serve as biomarkers of liver damage and inflammation. We studied miRNA-122 that is abundant in hepatocytes and miR-155, -146a and -125b that regulate inflammation in immune cells in mouse models of various types of liver diseases and found that serum/plasma miR-122 correlated with ALT increases in the liver damage. miR-155, a regulator of inflammation, was increased in serum/plasma liver injury associated with inflammation. Depending on the type of liver injury, circulating miRNAs showed association either with the exosome-rich or protein-rich compartments. Our results suggest that circulating miRNAs may serve as biomarkers to differentiate between hepatocyte injury and inflammation and the exosome versus protein association of miRNAs may provide further specificity to mechanisms of liver pathology.
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