Extracellular Biomarkers Summit, March 16-18, 2015  
Extracellular Biomarkers Summit, March 16-18, 2015 
Extracellular RNA in Drug and Diagnostic Development Banner

Extracellular RNA, which includes microRNA (the most frequently reported RNA class found outside of cells) and other types of RNA, is showing promise as minimally invasive biomarkers of various medically-relevant processes. Much of the progress in establishing the biological significance of extracellular RNA, also known as circulating RNA or cell-free RNA, is due to technological advances in next-generation sequencing and expression profiling, which has enabled quantitative and large-scale analysis of the cell-free transcriptome under different conditions. The Extracellular RNA in Drug and Diagnostic Development track of Extracellular Biomarkers Summit 2015 will focus on the analysis that correlates distinct extracellular RNA profiles with either the diagnosis or progression of specific diseases. Other drug discovery applications of extracellular RNA and its role in cell-to-cell communication will also be explored.

Day 1 | Day 2 | Download Brochure 

Tuesday, March 17

12:00 pm Conference Registration


Sequencing and Profiling Strategies for
Extracellular RNA Analysis
 

1:30 Chairperson’s Opening Remarks

Aleksandar Milosavljevic, Ph.D., Professor, Molecular and Human Genetics, Baylor College of Medicine

1:35 The Rat microRNA Body Atlas: Towards Understanding Serum microRNA Changes and Their Utilization as Biomarkers of Specific Organ Toxicity

Aaron Smith, Senior Toxicologist, Investigative Toxicology, Lilly Research Laboratories

microRNAs (miRs) have many attributes which have elicited considerable interest in their use as serum-based biomarkers of organ injury. In order to identify tissue specific/enriched miRs and to understand serum miR changes, we have constructed a rat miR body atlas using Illumina miR sequencing of 22 rat tissues of toxicologic interest. These data provide a valuable miR platform to identify serum miR changes reflecting their organ-specific origin during injury to the liver and pancreas in vivo.

2:00 MicroRNA Biomarkers Circulate in Multiple Biophysical States: Implications for Diagnostics Development

John Chevillet, Ph.D., Postdoctoral Research Fellow, Laboratory of Leroy Hood, Institute for Systems Biology

Circulating microRNAs have been reported to exist in multiple biophysical states, including most famously as cargo of 50-100 nm extracellular vesicles known as exosomes. Our understanding of circulating miRNA biomarkers is rapidly evolving and the development of sensitive, accurate and precise analytic approaches can be substantially assisted by a quantitative understanding of their distribution in physical and biochemical fractions of patient specimens.

2:25 Picoliter Droplet-Based Digital PCR and microRNA Quantification

Valerie Taly, Ph.D., Group leader, CNRS researcher, University Paris-Descartes

Droplet-based microfluidics has led to the development of highly powerful systems that represent a new paradigm in high-throughput screening where individual assays are compartmentalized within microdroplet microreactors. In particular, picoliter droplet-based digital PCR has recently demonstrated its pertinence to perform millions of single molecule reactions in parallel for the detection and quantification of cancer genetic markers. We will present the development and validation of this new technology for the multiplex detection of clinically relevant microRNA.

2:50 Selected Poster Presentations

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing


Extracellular RNA Analysis and Toxicity Biomarkers 

4:10 Chairperson’s Remarks

Matthew Roth, Ph.D., Assistant Professor & Co-Director, Bioinformatics Research Lab, Baylor College of Medicine; Data Management & Resource Repository of the Extracellular RNA Consortium (NIH)

4:15 Evaluation of Circulating microRNAs as Biomarkers of Toxicity in Drug Discovery

Tatiana Sharapova, Ph.D., Scientist I, Cellular and Molecular Biology, AbbVie

At AbbVie we conducted investigations designed to evaluate the potential utility of circulating miRNAs as biomarkers of drug induced toxicity in various tissues including testicular, pancreatic, renal and liver injuries. Altogether, the data indicate that serum and/or urinary miRNAs could have utility as biomarkers of toxicity and support the future development of multiplexed panels of miRNAs to monitor multiple toxic changes from a single sample.

4:40 Potential of Extracellular microRNAs as Biomarkers of Acetaminophen Toxicity in Children

Xi Yang, Ph.D., Research Biologist, Systems Biology, FDA/National Center for Toxicological Research

Recent studies of adults with acetaminophen (APAP) -induced liver injury have reported human serum microRNA-122 (miR-122) as a novel biomarker. The goal of this study was to examine blood and urine extracellular miRNAs as potential biomarkers for APAP liver injury in children. Our results demonstrate that urinary extracellular miRNAs (miR-375) have the potential to be used as biomarkers in children to detect APAP-induced hepatotoxicity in clinical practice.

5:05 Quantitative PCR Profiling for Selection of Candidate microRNA Kidney Damage Markers

Mira Pavkovic, Ph.D., Bayer Pharma AG, GDD-GED-Toxicology; currently Postdoctoral Fellow, Systems Pharmacology, Harvard

Extracellular microRNAs (miRNAs) have emerged as novel biomarkers (BMs) for various pathological states. Issues like low miRNA content in biofluids and questions concerning normalization strategies represent clear challenges in terms of detection methods and analysis workflows. To evaluate these issues for urinary miRNAs we performed rat studies with two differently acting nephrotoxicants and developed a possible analysis approach for selection of BM candidates from profiling data of urinary miRNAs using PCR.

5:30 Close of Day

Day 1 | Day 2 | Download Brochure 

Wednesday, March 18

7:30 am Morning Coffee


Challenges in Biomarker Applications of
Circulating RNA
 

8:00 Chairperson’s Remarks

Saumya Das, M.D., Ph.D., Assistant Professor, Medicine, Harvard Medical School

8:05 Bioinformatics Challenges

Aleksandar Milosavljevic, Ph.D., Professor, Molecular and Human Genetics, Baylor College of Medicine

8:30 Important Considerations for exRNA Biomarker Discovery

Louise C. Laurent, M.D., Ph.D., Assistant Professor, Reproductive Medicine, University of California San Diego Health Science

This presentation will cover work and lessons learned from the NIH External RNA Communication Consortium (ERCC) Sample and Assays Working Group.

8:55 Panel Discussion: Standardization Issues for Extracellular RNA Research

Moderator: Matthew Roth, Ph.D., Assistant Professor & Co-Director, Bioinformatics Research Lab, Baylor College of Medicine; Data Management & Resource Repository of the Extracellular RNA Consortium (NIH)

Panelists:

Louise C. Laurent, M.D., Ph.D., Assistant Professor, Reproductive Medicine, University of California San Diego Health Science

Tatiana Sharapova, Ph.D., Scientist I, Cellular and Molecular Biology, AbbVie

Aaron Smith, Senior Toxicologist, Department of Investigative Toxicology, Lilly Research Laboratories

Scott J. Tebbutt, Ph.D., Associate Professor, University of British Columbia, & CSO, PROOF Centre of Excellence, Vancouver, Canada

Xi Yang, Ph.D., Research Biologist, Systems Biology, FDA/National Center for Toxicological Research

  • RNA isolation and quantification challenges
  • Bioinformatics challenges unique to exRNA data
  • Microarrays v. qPCR v. RNA-Seq
  • Unique advantages of exRNA biomarkers
  • Rate limiting steps for progress in biomarker applications

9:50 Coffee Break in the Exhibit Hall with Poster Viewing


Long Non-Coding Extracellular RNA Biomarkers 

10:30 Chairperson’s Remarks

Louise C. Laurent, M.D., Ph.D., Assistant Professor, Reproductive Medicine, University of California San Diego Health Science 

10:35 Extracellular, Long Non-Coding RNA Markers for Lung Cancer

Lynn Hlatky, Ph.D., Professor, Medicine, and Director of Cancer Systems Biology, Tufts University

11:00 Circulating Ang2mRNA as a Prognostic Marker for Lung Cancer

Ana Coelho, Ph.D., Professor, Oncology, Portuguese Oncology Institute

Lung cancer remains a disease with a dismal prognosis. The development of prognostic markers would allow patients the choice of more aggressive and prolonged therapies. Circulating prognostic markers, such as mRNA levels, are practical tools, since peripheral blood samples are easy to obtain, not relying on the availability of adequate biopsy specimen. Moreover, circulating Ang-2 mRNA levels could help in the stratification of NSCLC patients and can easily be included in the design of preclinical studies.

11:25 PCA3: A Non-Invasive, Long Non-Coding RNA Marker of Prostate Cancer

Gerald W. Verhaegh, Ph.D., Senior Scientist, Laboratory of Jack Schalken, Department of Experimental Urology, Radboud University Medical Center

The PCA3 gene, encoding a long non-coding RNA, is over-expressed by prostate cancer cells in comparison with all other cells studied. The differential expression is great, permitting detection of the RNA in cancer cells shed into the urine after attentive digital rectal exam. Urinary PCA3 appears useful as a highly specific marker for prostate cancer.

11:50 Luncheon Presentation (Sponsored Opportunity Available) or Lunch on Your Own


Functional and Diagnostic Roles for Extracellular RNA 

1:30 pm Chairperson’s Remarks

Xi Yang, Ph.D., Research Biologist, Systems Biology, FDA/National Center for Toxicological Research  

1:35 Extracellular RNAs as Diagnostic Biomarkers of Cardiovascular Disease 

Yigal Pinto, Ph.D., Professor, Cardiology and The Heart Failure Research Center, Academic Medical Center, Netherlands 

Biomarkers have profoundly changed cardiology. By measuring circulating heart-specific proteins, diagnosis and management of the most important cardiac syndromes have dramatically changed. The next frontier is to combine different biomarkers into so-called multi-marker panels. Small RNAs like microRNAs are measurable in the circulation. This holds great promise as technologies emerge that allow us to measure with great accuracy multiple microRNAs together with standard protein biomarkers. This is expected to again redefine some major diagnostic and therapeutic areas in cardiology.

2:00 A Functional Role for Extracellular RNAs in Cardiac Remodeling

Saumya Das, M.D., Ph.D., Assistant Professor, Medicine, Harvard Medical School

As mortality from acute myocardial infarctions has decreased, its sequelae, heart failure and sudden cardiac death, have contributed significantly to disease burden. Novel insights into cardiac remodeling that follows the initial stress would provide novel biomarkers and therapeutic targets for cardiac remodeling. Here we describe our efforts to identify extracellular RNA biomarkers associated with cardiac remodeling using a microarray and an RNA-seq platform, and examine the possible functional role of selected ex-RNAs in disease pathogenesis.

2:25 Towards Establishing Blood-Based, RNA Diagnostics for Acute Heart Failure Recovery

Scott J. Tebbutt, Ph.D., Associate Professor, University of British Columbia, & CSO, PROOF Centre of Excellence, Vancouver, Canada

Severe inotrope-dependent acute heart failure (AHF) is associated with poor clinical outcomes. There are currently no well-defined biomarkers of response to treatment that can be used to guide treatment or evaluate recovery in this patient population. In the present study, we are characterizing microRNAs as novel and emerging tissue and circulating biomarkers of HF in patients with severe inotrope-dependent AHF over the first 30 days of medical management or mechanical circulatory support (MCS).

2:50 Close of Conference



Day 1 | Day 2 | Download Brochure