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Archive - Jul 21, 2020

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Four Studies by Students/Fellow in Professor Lorraine O’Driscoll’s Laboratory at Trinity College Dublin Are Presented at International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22)

Professor Lorraine O’Driscoll (photo), PhD, is Professor in Pharmacology and Irish Research Council Advanced Laureate at the School of Pharmacy and Pharmaceutical Sciences, and the Trinity Biomedical Sciences Institute of Trinity College Dublin in Ireland. Dr. O’Driscoll (https://pharmacy.tcd.ie/staff/odriscoll-cv.php?uname=lodrisc) (https://www.tcd.ie/research/profiles/?profile=lodrisc) is also the Coordinator and Principal Investigator of the TRAIN-EV Program (http://train-ev.eu/), which provides training to 15 PhD students in extracellular vesicles (EVs) for benefit in health and disease. Dr. O’Driscoll’s research group focuses on diagnostic, prognostic, and predictive biomarkers; discovering new therapeutic targets; cancer cells’ communication via extracellular vesicles (EVs), as well as the potential uses of EVs from mesenchymal stem cells (MSCs) in regenerative medicine and improving infant milk formula (IMF) by understand milk EVs. Three of Dr. O’Driscoll’s PhD students and one of her post-doctoral research fellows are presenting posters at the International Society for Extracellular Vesicles (ISEV) Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/). These four posters focus on EV release in triple-negative breast cancer, EV release inhibition in prostate cancer, analysis of EVs from drug-resistant and drug-sensitive cancer cells as potential predictive biomarkers in liquid biopsy, and optimizing methods for the separation and characterization of EVs from skim milk and infant milk formula. PhD student Niamh McNamee presented a poster (PF08.02) titled “Inhibition of Extracellular Vesicles in Triple-Negative Breast Cancer.” In her introduction, Ms. McNamee noted that triple-negative breast cancer (TNBC) is the most aggressive from of breast cancer.

Exosomes That Are Both Antigen-Specific & Carry a Selected Gene-Regulating miRNA Act at the Immune Synapse to Induce APC-Derived Secondary Suppressive Exosomes, A Unique Approach That May Have Treatment Applications in Cancer, Autoimmunity, & Allergy

At the International Society for Extracellular Vesicles 2020 Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/), Philip Askenase, MD, presented a poster (PT09.16) titled “Unique Dual Targeting Antigen-Specific and Delivered Chosen-Gene-Specific Regulating Primary Exosomes Acting at the Immune Synapse to Induce APC-Derived Secondary Effector T Cell Suppressive Exosomes.” Dr. Askenase is Professor of Medicine (Clinical Immunology) at the Yale University School of Medicine in the Section of Rheumatology and Clinical Immunology, and former Chief of Allergy & Clinical Immunology at the Yale University School of Medicine. In the ISEV poster, Dr. Askenase and colleagues report identification of a multi-exosome-APC (antigen-presenting cell) circuit that may be applicable far beyond the skin immunity these scientists study in mice. The researchers show results indicating they have been able to induce therapeutic exosomes that both specifically target a particular antigen on acceptor cells like APCs due to antibody light chains bound to the surface of the exosomes, and also target specific gene functions of the acceptor cells, due to delivery, in the exosome’s cargo, of a selected microRNA (miRNA). This dual antigen-specific (via the surface-bound antibody light chains) and gene-specific (via the exosome-associated selected miRNA) therapy may have applications in the treatment of cancer, autoimmunity, and allergy. In order to demonstrate this capability experimentally, Dr.

Second of Four Featured Abstract at ISEV 2020 Virtual Annual Meeting (July 20-22) Describes Initial Results of Efforts to Develop Reference Intervals for Extracellular Vesicles (EVs) in Human Plasma by Flow Cytometry

On Monday, June 20, in the second of four Featured Abstracts being presented by junior investigators during the ISEV 2020 Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/), Bo Li (photo), PhD, from the Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China (People’s Republic), presented her group’s abstract (FA04) “Towards Reference Intervals of Extracellular Vesicles in Human Plasma by Flow Cytometry.” In her introduction, Dr. Li noted that, although flow cytometers with submicrometer sensitivity can characterize single extracellular vesicles (EVs) in clinical samples, there is no consensus about the concentrations of EVs in plasma from healthy humans. To determine cut-off values for diagnoses, reference intervals of EVs in plasma are needed, Dr. Li asserted. To establish such reference intervals, Dr. Li said there are four requirements. First, a significant number of healthy donors should be included. Secondly, the presence of non-EV particles, residual platelets, lipoproteins, and hemolysis should be quantified. Thirdly, a clinically applicable protocol to avoid swarm detection should be established in advance. And lastly, flow cytometry signals should be in SI units. Dr. Li said that the long-term aim of this study is to determine reference intervals of EV concentrations in human plasma within known dynamic ranges of the detectors. In the experimental work to establish a clinical reference, Dr. Li and colleagues first collected blood from 224 healthy volunteers and prepared platelet-free plasma. Then, they performed quality-control measurements including residual platelet count, serum index, and lipid spectrum. They also determined that a protocol of 31-fold to 10(3) dilution is safe to prevent swarm detection in plasma from healthy donors.

First of Four Featured Abstracts at ISEV 2020 Virtual Annual Meeting (July 20-July 22) Focuses on How Ral-GTPases Promote Metastasis by Controlling Biogenesis & Organotropism of Exosomes; Breast Cancer Metastasis to Lung Is Subject of Study

On Monday, June 20), in the first of four Featured Abstracts being presented by junior investigators during the ISEV 2020 Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/), Shima Ghoroghi (photo), from Dr. Jacky Goetz’s Laboratory for Tumor Mechanics (http://www.goetzlab.com/team/), University of Strasbourg, France, delivered abstract FA01 “Ral-GTPases Promote Metastasis by Controlling Biogenesis and Organotropism of Exosomes.” Ms. Ghoroghi joined Dr. Goetz’s group as a PhD student in 2016 to study the role of Ral-GTPases in the secretion of exosomes by tumor cells during metastasis under close supervision of Dr. Vincent Hyenne, a specialist in exosomes. In her introduction, Ms. Ghoroghi noted that exosomes are small vesicles of endosomal origin, composed of different biomolecules including RNA, lipids, and proteins, which can be taken up by distant cells and deliver a functional message. Many studies have shown that exosomes play a major role in tumor progression by mediating the communication between tumors cells and their microenvironment. The main goals of Ms. Ghoroghi’s PhD project consist in dissecting the mechanisms of exosome secretion influenced by Ral-GTPases and understanding the importance of these exosomes in metastasis. During her PhD studies, Ms. Ghoroghi found that Ral-GTPases are central molecules linking the mechanisms of exosome secretion to their capacity to disseminate and induce pre-metastatic niches. She provided a detailed dissection of the impact of the Ral-GTPases on exosome secretion levels and content. She also showed that Ral-GTPases control exosome secretion by acting on the endosomal secretion pathway through the phospholipase D1 (PLD1), which also promotes exosome secretion.

International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22) Opens with Record 1,600 Attendees from Over 50 Countries

The International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting (July 20-22) (https://www.eventscribe.com/2020/ISEV/), with 1,600 virtual attendees from over 50 countries around the world, and offering ~600 presentations of various types (Plenary Addresses, “Hot Topic” Panel Sessions, Featured Abstracts, Oral Abstract Talks, Poster Chats, & Education Sessions), both live-streamed and on-demand, opened on Monday, July 20, with welcoming remarks by Alissa Weaver, MD, PhD Professor & Chair, Cell & Developmental Biology, Vanderbilt University School of Medicine, and Lucia Languino, PhD, Professor, Cancer Biology, Thomas Jefferson University, Philadelphia, the two ISEV International Organizing Committee (IOC) Co-Chairs, and by Ken Witwer, PhD, Associate Professor, Molecular and Comparative Pathobiology, Johns Hopkins, and ISEV Executive Chair for Science & Meetings. These warm words were followed by the meeting’s first live-streamed plenary address on the “The Mystery of EV Biogenesis—Past, Present, and Future,” presented by Phyllis Hanson, MD, PhD, Chair of Biological Chemistry at the University of Michigan. Dr. Hanson is a world-leading expert on the organization of cellular membranes. She studies how proteins interact with each other, and with membranes, to influence membrane trafficking and cellular organelles, and the way in which these interactions influence neurodegenerative diseases such as Alzheimer's disease. Dr. Hanson was introduced by her former colleague Dr. Weaver and Dr. Hanson’s address was followed by a 15-minute Q&A session moderated by Dr. Languino.

SECOND PLENARY ADDRESS FOCUSES ON "EVs IN NEUROLOGICAL DISEASES"