8:00 am Symposia Registration and Morning Coffee
8:55 Chairperson’s Opening Remarks
Edward J. Goetzl, M.D., University of California San Francisco
9:00 Exosome Diagnostics in Neurodevelopmental and Neurodegenerative Diseases
Edward J. Goetzl, M.D., Edward A. Dickson UC Professor, University of California San Francisco; Jewish Home of San Francisco Research Center; National Institute on Aging; Nanosomix, Inc.
The capacity to isolate cell source-specific plasma exosomes (PEs) has permitted establishment of new diagnostic and predictive platforms for human neural diseases. Quantities of primary and ancillary pathogenic proteins in neuronal-derived PEs predict both onset of Alzheimer’s disease (AD) up to 15 years before memory loss and conversion from mild cognitive impairment to dementia, and distinguish AD from frontotemporal dementia. Reduced levels of cellular survival factors in fetal neuronal-derived maternal PEs characterize fetal distress syndromes. Neural PE indices based on multiple analytes will soon be routine components of neural disease evaluations.
9:30 Del-1 on Exosomes as an Early Biomarker of Breast Cancer
Moon-Chang Baek, Ph.D., Associate Professor, Molecular Medicine, Kyungpook National University School of Medicine; Exxosome, Inc.
Del-1 protein on exosomes provides an early diagnostic biomarker for breast cancer and promotes breast cancer invasion via integrin-FAK signaling. The exosomes are sufficient for acceleration of lung micrometastasis. ELISA to detect Del-1-(+)cirExo in blood without exosome purification was developed.
10:00 Donor Tissue Specific Exosome Profiling as a Novel Biomarker Platform for Monitoring Transplant Organ Rejection
Prashanth Vallabhajosyula, M.D., Assistant Professor, Surgery, Hospital of the University of Pennsylvania
In patients undergoing transplantation, there is a critical need for accurate, non-invasive biomarker platforms for monitoring transplant organ rejection. We propose that all transplanted tissues release donor-specific exosomes into recipient blood/bodily fluids, and that its quantitation and molecular signature profiling would constitute a novel biomarker platform for monitoring transplant organ rejection.
10:30 Networking Coffee Break
11:00 Enabling Urine Extracellular Biomarker Isolation
Shannon Pendergrast, Ph.D., CSO, Ymir Genomics
The discovery of urinary extracellular biomarkers has been impeded by the lack of efficient methods for the isolation of extracellular vesicles. Ymir Genomics has invented a novel precipitation reagent (Ymirite) that rapidly and efficiently isolates extracellular vesicles from urine samples yielding a quantity suitable for biomarker discovery.
11:30 Vesicle Flow Cytometry: High Resolution Characterization of Individual Extracellular Vesicles
John P. Nolan, Ph.D., Professor, Scintillon Institute
Living cells release small extracellular vesicles (EVs) into the intercellular space. Biofluids such as plasma and cerebrospinal fluid (CSF) contain EVs released various different cells that can reveal information about the cells of origin, making them potential biomarkers. However, EVs are small and heterogeneous and a lack of effective analytical tools has prevented this potential from being realized. We have developed new instruments, reagents and assays for the sensitive and quantitative analysis of individual EVs. I will present data on the concentrations, sizes, and immunophenotypes of EVs in plasma and CSF in normal and diseased states.
12:00 pm All Things Being Equal: Approaches to Normalizing Exosomal Biomarkers
Peter Yuen, Ph.D., Staff Scientist, Renal Diagnostics & Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Exosomal biomarkers can potentially answer important clinical and biological questions. These answers have limitations, depending on the context of the questions being asked. Normalization, when done correctly, can overcome some of these limitations. I outline a framework for how to approach the proper normalization strategy and our current progress on normalization methods for exosomal biomarkers.
12:30 Enjoy Lunch on Your Own
1:55 Chairperson’s Remarks
Theresa L. Whiteside, Ph.D., MDHC, University of Pittsburgh Cancer Institute
2:00 Human Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune Suppression
Theresa L. Whiteside, Ph.D., MDHC, Professor, Pathology, Immunology and Otolaryngology, University of Pittsburgh Cancer Institute
Emerging evidence suggests that tumor-derived exosomes (TEX) present in body fluids of cancer patients potentiate Treg cell-mediated suppression and inhibit effector functions of T lymphocytes. TEX carry immunosuppressive cargos (e,g., CD39 and CD73 or TGF-β1-associated proteins or PD1/PD-L1). When co-incubated with T cells, TEX alter mRNA and protein expression profiles in these cells, enhancing their suppressive activity. Efforts are in progress to develop methods for capture of “pure” TEX from plasma of cancer patients and determine their value as biomarkers of immune dysfunction in cancer.
2:30 Extracellular Vesicles and Driver Gene Mutation in Cancer
Subrata Sen, Ph.D., Professor and Deputy Chair, Translational Molecular Pathology, University of Texas MD Anderson Cancer Center
There is growing evidence of critical roles of cancer cell-derived extracellular vesicles/exosomes in reprogramming of the tumor microenvironment. Utilizing an in vitro cell line model of cancer progression, we are investigating the role of driver gene mutations in regulating structure and function of cancer cell-derived extracellular vesicles/exosomes.
3:00 Networking Refreshment Break
3:30 Role of Tumor Exosomes in Immune Suppressionand Cancer Progression
Huang-Ge Zhang, M.D., D.V.M., Ph.D., Professor, Microbiology & Immunology, University of Louisville
4:00 Role of Exosomic microRNAs in the Biology of the Tumor Microenvironment
Muller Fabbri, M.D., Ph.D., Assistant Professor, Pediatrics, Molecular Microbiology & Immunology, USC Keck School of Medicine, Children’s Hospital LA
Exosomes are small vesicles involved in intercellular communication. Among the cargo molecules of exosomes, microRNAs elicit a central function in orchestrating the biology of the tumor microenvironment. This lecture will focus on a newly identified role for microRNAs, as ligands of a specific receptor (miRceptor) in tumor-associated macrophages (TAMs). As a result of this miR-miRceptor interaction, TAMs secrete cytokines and other exosomic microRNAs that shape the tumor microenvironment towards promoting tumor growth and resistance to therapy.
4:30 Focal Adhesion Kinase (FAK) is Differentially Expressed in Microvesicles Generated by Transformed Cells
Marc Antonyak, Ph.D., Senior Research Associate, Molecular Medicine, Cornell University
Microvesicles mediate cell-to-cell communication events that promote cancer progression. Here we determined the differences between microvesicles generated by normal cells and those formed by transformed cells. We found that, while both of these cell types generated similar amounts of microvesicles, only the microvesicles shed by the transformed cells promoted cell survival. We then showed that the differential expression of the signaling protein FAK in these microvesicles accounted for their survival-promoting capabilities.
5:00 Close of Symposium