Conference Agenda

This is an unprecedented time in biomolecular medicine. Recent scientific findings have determined biofluids consist of circulating cell-free (ct)DNA and extracellular (ex)RNA from multiple tissues within the body. In addition, the rapid development of highly sensitive and accurate next-generation sequencing (NGS) technologies has empowered researchers to analyze the role of these biomolecules in health, disease and treatment response. However, there remains considerable insecurity associated with biofluid-based DNA/RNA analytical methods which must be solved before liquid biopsies can be implemented for broader routine applications. With refinements in the process and technology, molecular liquid biopsies have the potential to become a fulcrum in the future of precision medicine.

Final Agenda

Wednesday, June 22

3:45 pm Main Conference Registration

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

6:30 Close of Day

Thursday, June 23

8:00 am Morning Coffee

Oncology: Liquid Biopsies Are Advancing into the Clinic

8:30 Organizer’s Opening Remarks

Mary Ann Brown, Executive Director, Conferences, Cambridge Healthtech Institute

8:35 Chairperson’s Opening Remarks

Jamie Platt, Ph.D., MB(ASCP), Founder & Managing Director, BRIDGenomics, LLC

9:30 Circulating RNAs as Noninvasive Biomarkers in Colorectal Cancer

Ajay Goel, Ph.D., Investigator/Professor & Director, Center for Gastrointestinal Research; Director, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center

Noncoding RNAs (ncRNAs) are emerging as important regulators of gene expression in cancer. Overexpression of specific noncoding RNAs (including microRNAs, SnoRNAs, piRNAs and circular RNAs) has been linked to the stepwise disease progression in colorectal cancer (CRC). Given their cancer-specific pattern of expression, remarkable stability and presence in blood and other body fluids, ncRNAs are considered to be highly promising “liquid biopsy” cancer biomarkers. Accumulating evidence firmly supports the existence of unique “ncRNA signatures” that can not only facilitate earlier detection of the tumor, but can also assist in predicting disease recurrence and therapeutic outcome to current treatment regimens.

10:00 Accessing Genetic Information with Liquid Biopsies

Jian-Bing Fan, Ph.D., CEO, AnchorDx Corp.

The molecular liquid biopsies approach provides non-invasive access to genetic information – somatic mutations, epigenetic changes, and differential expression – about the physiological conditions of our body and diseases. With the rapid development of highly sensitive and accurate technologies such as next-generation sequencing, it is now possible to reliably analyze CTCs and circulating nucleic acids in a clinic setting, which opens a valuable avenue for future genetic studies and human disease diagnosis.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 Analytic Validation of an NGS-Based Clinical ctDNA Assay

Geoff Otto, Ph.D., Senior Director, Molecular Biology & Sequencing, Foundation Medicine

Profiling circulating tumor DNA (ctDNA) for the genomic alterations (GA) driving oncogenesis promises to provide insight into cancer biology, inform therapy selection when conventional biopsies are unobtainable and enable monitoring of response to therapy. A clinical, NGS-based ctDNA assay was developed, highly accurate detection of GA was analytically validated and clinical utility investigated from patient-matched FFPE and blood samples across lung, breast and colon cancer at different disease stages.

11:30 Nucleosome Footprints in Cell-Free DNA Are Evidence of Its Tissues of Origin

Andrew Hill, Graduate Research Fellow, Jay Shendure Laboratory, Genome Sciences, University of Washington

Nucleosome positioning varies across cell types. Some proportion of cell-free DNA (cfDNA) is protected by nucleosomes, which in principle could allow detection of cell types contributing to cfDNA. We infer nucleosome positioning in cfDNA to identify abnormal contributions in pathologies such as cancer. Because this method does not rely on genetic differences between healthy and pathological contributions, it could potentially broaden the scope of cfDNA-based monitoring and diagnostics.

12:00 pm From Sample to Insight – Pioneering the Liquid Biopsy Revolution
Michael Kazinski, Senior Director, Molecular Pre-analytical Technologies, QIAGEN 
Liquid biopsy has potential to transform healthcare and biomedical research. This presentation provides an overview on QIAGEN’s approach to integrated solutions, ranging from isolation to bioinformatics interpretation, for the purpose of isolating and characterizing circulating nucleic acids as biomarkers in research and development applications. 

12:30 Lunch on Your Own

Tools that Capture, Amplify and Analyze
Minute Amounts of Nucleic Acids

2:00 Chairperson’s Remarks

Ellen M. Beasley, Ph.D., Senior Vice President, Product & Services Research & Development, Business & Product Development, Genomic Health, Inc.

2:05 Nanocarbon-Coated Porous Anodic Alumina for Biological Applications

Steven Prawer, Ph.D., D.Sc., Professor of Physics, School of Physics, University of Melbourne

Here we demonstrate a new broad-range sensor platform for ultrasensitive and selective detection of circulating DNA down to the single-molecule level. The biosensor is based on a chemically functionalized nanoporous diamond-like carbon (DLC)-coated alumina membrane. The few nanometer-thick, yet perfect and continuous DLC coating confers the chemical stability and biocompatibility of the sensor, allowing its direct application in biological conditions.

2:35 T Oligo-Primed Polymerase Chain Reaction (TOP-PCR): A Robust Method for the Amplification of Minute Amount of DNA Fragments from Body Fluids

Kuo Ping Chiu, Ph.D., Associate Research Fellow, Genomics Research Center, Academia Sinica

We have developed T oligo-primed PCR (TOP-PCR) for comprehensive amplification of minute DNA fragments. TOP-PCR adopts homogeneous adaptor (generated by P oligo and T oligo) for efficient ligation to A-tailed DNA, followed by PCR amplification primed by T oligo. We demonstrate that TOP-PCR maintains the size profile of the DNA sample and is a superior method for recovering minute DNA in body fluids. It maximizes the resolution of Illumina sequencing.

3:05 Poster Spotlight: Isolation of Circulating Tumor Cells from Patients with Metastatic Colorectal Cancer Using Label-Free Microfluidic Technology for Enumeration and Detection of KRAS, BRAF, PIK3CA Mutation

Steve Crouse, Chief Commercial Officer, Vortex Biosciences

To compare mutational profiles between primary, secondary tumors and CTCs, 24 CTC samples, 9 liver metastases and 3 primary FFPE tumor samples were analyzed from 9 patients, with Sanger sequencing of KRAS, BRAF and PIK3CA gene mutations. 77.8% concordance was obtained between metastatic tissue and CTCs (7/9 patients). Vortex technology offers an efficient label-free method to isolate CTCs with high purity to enable sensitive and accurate mutation analysis of CTCs.

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

4:00 Looking for the Free Agents in Blood: High-Sensitivity RNA-Seq Approaches for Detecting Infectious Agents in Liquid Biopsies

Andrew Brooks, Ph.D., COO, RUCDR Infinite Biologics; Associate Professor, Genetics, Rutgers University

4:30 Sample Prep in Liquid Biopsy; Can We Always Win the Lottery?

Jamie Platt, Ph.D., MB(ASCP), Founder & Managing Director, BRIDGenomics, LLC

The introduction of NGS has enabled some remarkable applications which allow for less invasive specimen acquisition, and improved sensitivity and specificity. Liquid biopsy is one application that holds enormous promise as a tool for monitoring therapeutic response, detect residual disease, and even provide an earlier diagnosis. However, one fact remains: you can’t detect what you haven’t sampled. The key issues and opportunities for liquid biopsy sample prep will be discussed.

5:00 Next-Generation Liquid Biopsy: Tumor Monitoring from Droplet Volumes of Blood

Chen-Hsiung Yeh, Ph.D., CSO, Circulogene Theranostics

Circulating cell-free DNA (cfDNA) can provide a global longitudinal picture of tumor heterogeneity. Large sample volume, low yield, and labor intensiveness are major obstacles for clinical application of cfDNA-based testing. Our proprietary cfDNA sample preparation breakthrough enables clinicians to work with a sample volume as small as 20 microliters (via a finger prick), which can further expedite clinical decision-making and identify targeted therapies for eligible patients in a time- and cost-efficient manner.

5:30 Close of Day

Friday, June 24

7:30 am Breakfast Breakout Discussion Groups

Chew over breakfast and provocative discussion topics with your peers. These are moderated discussions with brainstorming and interactive problem solving, allowing conference participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic.

Standards of Evidence, Methods and Materials to Accelerate Liquid Biopsy Development and Adoption

Moderator:
Ellen M. Beasley, Ph.D., Senior Vice President, Product & Services Research & Development, Business & Product Development, Genomic Health, Inc.

• What standards should we expect for analytical validation of liquid biopsy assays and how should data be presented?
• What role do clinical concordance, clinical validation and clinical utility studies play in supporting liquid biopsy assay launch, adoption and reimbursement?
• How can liquid biopsy assays benefit from community data generation efforts and what data should still be generated for each assay?

Use of Systems or Computational Biology to Decipher the Molecular Information that Arises from High-Throughput Liquid Biopsies from the Plasma

Moderator:
Stephen Y. Chan, M.D., Ph.D., Director, Center for Pulmonary Vascular Biology and Medicine; Associate Professor of Medicine, Department of Medicine, University of Pittsburgh Medical Center

• What types of biological questions are amenable for a systems biology approach to liquid biopsies?
• Differentiating the bioinformatic processes of genomic/transcriptomic analysis from higher-order network analysis
• Can a systems biology analysis of plasma allow for insight into tissue biology?

NGS for Clinical Infectious Disease Diagnostics

Moderator:
Charles Chiu, M.D., Ph.D., Associate Professor, Laboratory Medicine and Medicine/Infectious Diseases; Director, UCSF-Abbott Viral Diagnostics and Discovery Center; Associate Director, UCSF Clinical Microbiology Laboratory, UCSF School of Medicine, University of California, San Francisco

Nanoscience in the Service of Biological Technologies

Moderator:
Steven Prawer, Ph.D., D.Sc., Professor of Physics, School of Physics, University of Melbourne

• Enormous progress is being made every day in the development of designer nanomaterials and nanodevices. But how do we determine which of the latest developments in nanotechnology are likely to have the largest impact on medical diagnostics in general and liquid biopsy in particular?
• What models of collaboration work best to allow clinicians and technologists to learn of each other's capabilities and needs so that promising technologies can be rapidly identified and prototype development accelerated?

Future of Circulating Tumor Cells (CTC) in Clinical Practice

Moderator:
Siddarth Rawal, M.D., COO, Circulogix Inc.; Clinical Research Associate, Miller School of Medicine, University of Miami

• An enormous amount of research has been on going in the field of CTC and numerous companies are coming out with CTC capture and analysis platforms. But how useful do clinicians view this data in their day-to-day decision-making?
• Are the tests at a point where they are robust, reproducible and consistent across laboratories?
• All CTC assays are currently research use only. What must happen for these tests to be standardized, inexpensive and acceptable to insurance companies to be used as a clinical test?

Moving Beyond Cancer: Tackling Other Targets

8:45 Chairperson’s Opening Remarks

Charles Chiu, M.D., Ph.D., Associate Professor, Laboratory Medicine and Medicine/Infectious Diseases; Director, UCSF-Abbott Viral Diagnostics and Discovery Center; Associate Director, UCSF Clinical Microbiology Laboratory, UCSF School of Medicine, University of California, San Francisco

8:50 Cell-Free DNA in Transplant Medicine

Kiran K. Khush, M.D., MAS, FACC, Associate Professor, Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine

This talk reviews clinical applications of cell-free DNA testing in the field of solid organ transplantation. Topics covered include (1) monitoring for acute rejection, with illustrative cases from heart and lung transplantation, (2) monitoring of the transplant recipients’ virome, and how it changes with introduction and weaning of immunosuppression, and (3) non-biased detection of disease-causing pathogens in transplant recipients.

9:20 Liquid Biopsy of the HIV Latent Reservoir in Patients on Anti-Retroviral Therapies

Xiaohe Liu, Ph.D., Senior Scientist & Co-Leader, Rare Cell Technology Program, Biosciences Division, SRI International

A major hurdle in HIV eradication research is the lack of robust assays to characterize the reservoir cells that harbor HIV in the presence of anti-retroviral therapy (ART). We applied FAST (Fiber-optic Array Scanning Technology) to detect and characterize rare cells that express HIV proteins in peripheral blood of patients on ART. Our data suggest that FAST may be a new, important method to identify and measure replication competent proviruses.

9:50 Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Diseases from Cell-Free Fluids

Charles Chiu, M.D., Ph.D., Associate Professor, Laboratory Medicine and Medicine/Infectious Diseases; Director, UCSF-Abbott Viral Diagnostics and Discovery Center; Associate Director, UCSF Clinical Microbiology Laboratory, UCSF School of Medicine, University of California, San Francisco

Metagenomic next-generation sequencing (mNGS) is a powerful approach to the diagnosis of infectious diseases, as it does not rely on targeted primers or probes. A single sequencing test is able to identify all viruses, bacteria, fungi, and parasites in clinical samples. Here we describe implementation of a clinically validated mNGS assay from cerebrospinal fluid to diagnose meningitis and encephalitis in critically ill hospitalized patients.

10:20 Coffee Break in the Exhibit Hall with Poster Viewing

10:55 Sample Prep in Genetic Assay Development

Toumy Guettouche, Ph.D., Director, Early Development & Genetics Assay Development, Sequencing Unit, Roche Molecular Systems

11:25 Using Immune Profiles to Categorize Neurological Disease

Nancy Monson, Ph.D., Associate Professor, Department of Neurology and Neurotherapeutics & Department of Immunology, University of Texas Southwestern Medical Center

Cerebrospinal fluid (CSF) samples have been a useful tool in the diagnosis of neurological diseases involving the central nervous system (CNS). Our laboratory has focused on finding new ways to use CSF as a diagnostic tool for multiple sclerosis, an autoimmune disease of the CNS. We discovered that antibody genetics of CSF-derived B cells can be used to identify patients who have MS and patients who will develop MS in the future with 84-92% accuracy.

11:55 Networking Luncheon (All Are Welcome)

Detecting the Role of Extracellular RNAs
in Health and Disease

1:30 Chairperson’s Remarks

Lynne T. Bemis, Ph.D., Chair, Biomedical Sciences, University of Minnesota

2:20 The Biology of Circulating MicroRNAs in Cardiovascular Health and Disease

Stephen Y. Chan, M.D., Ph.D., Director, Center for Pulmonary Vascular Biology and Medicine; Associate Professor of Medicine, Department of Medicine, University of Pittsburgh Medical Center

Plasma-based circulating microRNAs have attracted attention in cardiovascular medicine, relevant for the study of disease states and normal physiology. I describe our recent findings regarding the dynamic regulation and biological actions of circulating microRNAs in aerobic exercise and in pulmonary hypertension. I discuss new technologies to detect and quantify these factors. Finally, I discuss the potential utility of circulating microRNAs as putative cardiovascular biomarkers and/or therapeutic targets.

2:50 Poster Spotlight: An Enabling Platform for the Detection of Plasma Circulating MicroRNAs in the Low Resource Setting

Monika Martick, Ph.D., Associate Scientist, Miroculus

Accurate detection and measurement of microRNAs in biofluids can be achieved by a number of technologies, but their complexity limits the utility of miRNAs as biomarkers to centralized laboratories that are equipped with state-of-the-art instrumentation. To surpass this limitation, Miroculus has developed a low-cost microRNA detection platform designed for laboratory technicians without specialized training and in a low-resource setting.

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

3:30 Comparison of Extracellular RNA Profiles across Biofluids and Their Utility for Biomarker Development

Kendall Van Keuren-Jensen, Ph.D., Associate Professor, Neurogenomics, TGen

Examination of RNA species from several biofluids can provide a range of information about an individual. For example, there are varying amounts of tissue-specific data and exogenous RNA species present among different biofluids. Depending on the type of disease or location of injury, the choice of biofluid may be an important consideration for biomarker development.

4:00 tRNA Fragments Join the Repertoire of Small RNAs with Potential as Biomarkers

Lynne T. Bemis, Ph.D., Chair, Biomedical Sciences, University of Minnesota

tRNA fragments are often abundant in high-throughput studies of extracellular RNA. Initially regarded as breakdown products of mature tRNA, and thus of little consequence, they are now being studied for their regulatory function in health and disease. A review of our current understanding of the functions attributed to these fragments will be presented.

4:30 Close of Conference