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microRNA as Biomarkers and Diagnostics Conference - Day 2


Conference Proceeding CD Now Available
  • Speaker Presentations
  • Poster Abstracts
  • and More!

Day 1 | Day 2 | Short Courses 


Tuesday, March 18

7:30-8:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:30-9:30 Roundtable Discussions

Roundtable discussions are interactive, topic-specific discussions hosted by expert moderators and open to all attendees. These sessions provide a forum for discussing key issues.

• Topic 1: How to Choose a microRNA Normalization Strategy
Moderator: Christos Argyropoulos, M.D., MSc, Ph.D., Medical Affairs Consultant

• Topic 2: Detection of Circulating microRNAs
Moderator: Brian Johnston, Ph.D., President and CEO, SomaGenics

• Topic 3: microRNA Analysis in Tissue Specimens

Moderator: Lorenzo F. Sempere, Ph.D., Assistant Professor, Center for Personalized Medicine, Van Andel Research Institute


microRNA as Disease Biomarkers 


9:30-9:35 Chairperson’s Opening Remarks

Sok Kean Khoo, Ph.D., Distinguished Associate Professor, Molecular Genomics, Department of Cell & Molecular Biology, GVSU Michigan

9:35-10:00 MicroRNAs as Blood-Based Biomarkers

Martin Beaulieu, Ph.D., Director, MicroMarkersTM , Regulus Therapeutics

Recent studies show that miRNAs are released from tissues into the circulation and the levels of specific miRNAs can be used as surrogates for the disease tissues. miRNAs are highly stable in the circulation due to the fact that they are protein bounded and/or encapsulated in vesicles. These attributes of miRNAs have sparked an intense interest to identify miRNAs in the circulation that can be used as easily accessible biomarkers of different disease states. Highly sensitive and well-established technologies including real time quantitative PCR are available to quantitatively detect miRNAs. Similar to identifying biomarkers using other analytes, consistent extraction method and purifying platform, high standard in statistics and study design are essential for identifying biomarkers with clinical utilities. We have developed and optimized a high-throughput platform that consistently detects over a hundred miRNAs from less that 200 microliters of serum. Using this optimized platform and workflow, we are conducting large-scale profiling studies to identify serum miRNA biomarkers in a wide variety of disease conditions.

10:00-10:25 Urinary miRNA Patterns in Type 1 Diabetes: Implications for Prognosis and Pathogenesis of Diabetic Nephropathy

John P. Johnson, M.D., Professor, Medicine, Cell Biology and Physiology, University of Pittsburgh

Christos Argyropoulos, M.D., MSc, Ph.D., Medical Affairs Consultant

In recent years microRNAs have emerged as important post-transcriptional regulators of gene expression, yet clinical data in important diseases are lacking. We found that urinary microRNAs of patients with type 1 diabetes differ across the stages of kidney disease, even in the absence of conventional markers of kidney involvement (microalbuminuria). Combining expression ratios of microRNAs with predictions about their targets may yield useful markers for early diagnosis and risk stratification of patients by inferring the alteration of renal molecular processes.

10:25-10:55 Profiling microRNAs in Breast Cancer by Flow Cytometry Using SmartRNAplex™ Profiling Assay: A Unique microRNA Detection Platform

Mark Santos, R&D Manager for Research Content & Reagents, EMD Millipore

The SmartRNAplex™ assay can simultaneously detect up to 68 unique microRNA targets per sample across a 96 well plate. Here we profile the expression of microRNA targets in both tumor breast tissues and adjacent normal breast tissues derived from the same patient.  By using SmartRNAplex™ technology we identify which microRNAs are present in breast tissue, and further assess which of these microRNAs are up-regulated in breast tumors when compared to normal breast tissue.

10:55-11:45 Coffee Break in the Exhibit Hall with Poster Viewing

11:45-12:10 pm Hepatic C Virus-Induced Modulation of Host microRNAs Is No mirage: Novel Biomarkers for Liver Disease

John Paul Pezacki, Ph.D., Senior Research Officer and Group Leader, Life Sciences, National Research Council of Canada

microRNAs (miRNAs) are small RNAs that post-transcriptionally regulate gene expression. Their aberrant expression is commonly linked with diseased states, including hepatitis C virus (HCV) infection. I will present data demonstrating that HCV induced modulations of microRNA expression contribute to HCV pathogenesis. Our work has shown that HCV replication induces the expression of miR-27 in cell culture and in vivo HCV infectious models, and this promotes the formation and accumulation of larger lipid droplets in the liver, clinically consistent with HCV associated steatosis, which is prevalent in >50% of infected patients.

12:10-12:35 Circulating microRNAs in Plasma as Predictive Biomarkers for Parkinson’s Disease: A New Paradigm

Sok Kean Khoo, Ph.D., Distinguished Associate Professor, Molecular Genomics, Department of Cell & Molecular Biology, GVSU Michigan

Parkinson’s disease (PD) is a complex neurological disorder caused by progressive loss of dopaminergic neurons, leading to motor, cognitive, and gastro-intestinal dysfunctions. Due to the subtle nature of its motor symptoms which current clinical diagnosis is majorly based on, neurodegeneration has reached a relatively advanced stage by the time of diagnosis. Here, we identify and develop a panel of circulating microRNA (miRNAs) in plasma as biomarkers for PD. The biomarkers achieve the predictive power of 91% sensitivity and 100% specificity.

 

12:35-1:05 Luncheon Presentation: Beyond Known microRNAs: Exploring the Rest of the Small RNA Transcriptiome

Byung-in Lee, Vice President, Product Operations, Maverix Biomics, Inc.

Within the human transcriptome, microRNAs have proven to be the most dynamic, functionally important class of small non-coding RNAs, influencing the regulation of the majority of protein coding genes. To enable hands-on exploration of RNA-seq data sets by a much larger community of biologsts, we have developed the Maverix Analytic Platform, integrating tools and data at the command of any researcher. We show examples of small RNAs to illustarte the untapped opportunities for discovery.

 


microRNA Biomarkers as Cancer Diagnostics 


1:50-1:55 Chairperson’s Opening Remarks

Prasun J. Mishra, Ph.D., Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH

1:55-2:20 Advancing Molecular Diagnostics and Precision Medicine Using Non-Coding RNA Variants

Prasun J. Mishra, Ph.D., Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH

Cumulative evidence now suggests that specific miRNAs and genetic variations interfering with miRNA function (miRNA polymorphisms) are involved in the prognosis and progression of a variety of diseases and can serve as biomarkers to predict drug response. Detection of prognostic-miRNAs and miRNA polymorphisms can potentially improve diagnosis, treatment and prognosis in patients and has profound implications in the fields of pharmacogenomics and precision medicine.

2:20-2:45 MicroRNAs as Central Players in the Biology of the Tumor Microenvironment: When Decoding miRNA Riddles Leads to Personalized Medicine

Muller Fabbri, M.D., Ph.D., Assistant Professor, Pediatrics and Molecular Microbiology & Immunology, University of Southern California Keck School of Medicine, Children’s Hospital Los Angeles

Increasing evidence indicates that not only cancer cells but also surrounding cells, forming the so-called “tumor microenvironment” play a key role in cancer biology. microRNAs contribute to the development of the malignancy also by communicating between cells of the tumor microenvironment, exchanged as secreted molecules inside of exosomes. Exosomic miRNAs exert their function through previously unknown mechanisms of action. A better understanding of such mechanisms represents the necessary rationale for the development of new personalized treatments for cancer patients.

2:45-3:10 Tissue Slide-Based microRNA Diagnostics for Cancer Medicine

Lorenzo F. Sempere, Ph.D., Assistant Professor, Center for Personalized Medicine, Van Andel Research Institute

microRNA diagnostics is an emerging area of prognostic and predictive indicators in cancer medicine. Tissue slide-based assays are routine diagnostic procedures in clinical laboratories to guide treatment options. To facilitate clinical integration of microRNA biomarkers, we implemented a fully automated tissue slide-based staining assay in a CLIA-certified environment. Here, we describe uses of this assay to measure levels and cellular compartment(s) of microRNA expression in solid tumors and discuss potential diagnostic applications of salient microRNA examples, including miR-21 and miR-34a.

3:10-3:40 Coffee Break in the Exhibit Hall with Poster Viewing

3:40-4:05 MicroRNAs as Predictive and Prognostic Biomarkers in Colorectal Cancer

Jingfang Ju, Ph.D., Associate Professor, Co-Director, Translational Research, Pathology, Stony Brook University

5-FU based chemotherapy (e.g. FOLFOX) is the standard chemotherapeutic regimen for treating advanced stage colorectal cancer. Chemoresistance is the major reason for the failure of treating advanced colorectal cancer. Our laboratory has identified several miRNAs (miR-192, miR-215, miR-140, miR-129, let-7, miR-181b, miR-200s) that are critical for the contribution to chemoresistance by regulating key cell death pathways such as apoptosis and autophagy. We have identified several important miRNA regulated targets such as Bcl2, thymidylate synthase, dihydrofolate reductase, histone deacetylase, and E2F. More importantly, these miRNAs can help predict patients who will benefit from the treatment with good response and long-term survival.

4:05-4:30 MicroRNA Profiling of Circulating Tumor Cells from Osteosarcoma

Benjamin Ory, Ph.D., Associate Professor, Therapy Primary Bone Tumor, Nantes Medical School, INSERM

Through the isolation of the rare circulating tumor cells (CTCs) in the blood stream, we uncovered some basic functional roles of the miRNAs in the regulation of pathways involved in the regulation of the cellular migration and invasion, responsible for the metastasis dissemination of osteosarcoma. This study might provide new valuable tools for the clinicians such as predictive markers for metastasis development directly from the analysis of a blood sample.

4:30-4:55 Development and Validation of miRNA Signature to Predict Clear Cell Renal Cell Carcinoma Metastasis and Prognosis

Huiqing Wu, M.D., Assistant Professor, Pathology, City of Hope National Medical Center, Beckman Research Institute

Using frozen tissue cohorts, microarray technology and risk score method, we identified a 4-miRNA signature associated with clear cell renal cell carcinoma (ccRCC) metastasis and prognosis. We converted the signature to a formalin-fixed paraffin-embedded (FFPE) tissue-specific and RT-PCR based assay. We further valeted the signature in an FFPE tissue cohort of 222 cases of primary ccRCC, with an overall sensitivity and specificity of 70% and 76%. Specifically, the sensitivity and specificity for predicting metastasis from stage I and II patients are 59% and 74%, from stage III patients are 80% and 83%. The signature is highly associated with the patient's cancer-specific survival.

 

4:55 Close of Conference

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