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April 27th, 2015

Closing Ceremony of 2015 Annual Meeting of the International Society for Extracellular Vesicles (ISEV) Features Awards, Research Summary, Clinical Summary, and On to Rotterdam in 2016!

At the end of Dr. Gary Ruvkun’s plenary address, Dr. Jan Lötvall, President of the International Society for Extracellular Vesicles (ISEV) (http://www.isevmeeting.org/), stepped forward to chair the closing ceremony of this “exciting and most interesting” 2015 annual ISEV meeting. First, Dr. Lötvall introduced Andy Hill, Ph.D., Professor and Department Head at the La Trobe Institute for Molecular Sciences at La Trobe University in Melbourne, Australia, to present a “wrap-up” of the scientific research presented at the meeting. Dr. Hill highlighted a number of areas of keen interest. These included EV biogenesis, isolation and characterization of EVs/exosomes, vesicle labeling, imaging (including super-resolution, confocal, intravital, and EM microscopy), nomenclature, and transcriptomics/RNA analysis. He also emphasized the great success of this year’s newly added “Meet the Experts” sessions. Next, Dr. Lötvall introduced Louise Laurent, M.D., Ph.D., an Assistant Professor, an obstetrician specializing in high-risk pregnancies, and a prominent EV researcher from the University of California, San Diego (UCSD), to give a wrap-up of the meeting from a clinical perspective. Dr. Laurent began by outlining where we are today, which she said is at the stage of discovering biomarkers and determining mechanisms, and where we are going in the future, which she said is in the direction of identifying druggable targets that might be EV-based and enable further development of personalized medicine. She emphasized that clinical progress in this area will depend critically on collaborations and cross-talk to speed advances. Communication needs to be “reciprocal,” she said, not “sequential.” Dr. Laurent also highlighted the needs for increased standardization and concern for reproducibility.

World Expert on RNA Interference (RNAi) and Small RNAs Gives Plenary Address on Final Day of 2015 Annual Meeting of International Society for Extracellular Vesicles (ISEV) in Washington, DC

On Sunday, April 26, the final day of the 2015 Annual Meeting of the International Society for Extracellular Vesicles (ISEV) (http://www.isevmeeting.org/), with a special focus on exosomes, the 800+ attendees were privileged to hear a plenary address from one of the world’s foremost authorities on small RNAs and RNA interference (RNAi), Gary Ruvkun (photo), Ph.D. Dr. Ruvkun is a molecular biologist at Massachusetts General Hospital and Professor of Genetics at Harvard Medical School. Dr. Ruvkun discovered the mechanism by which lin-4, the first microRNA (miRNA) discovered by Dr. Victor Ambros, regulates the translation of target messenger RNAs via imperfect base-pairing to those targets, and also discovered the second miRNA, let-7, and demonstrated that it is conserved across animal phylogeny, including in humans. These miRNA discoveries revealed a new world of RNA regulation at an unprecedented small size scale, and the mechanism of that regulation. Dr. Ruvkun has also discovered many features of insulin-like signaling in the regulation of aging and metabolism. Given that the cargo of exosomes and other extracellular vesicles frequently includes varieties of small RNAs, particularly miRNAs, Dr. Ruvkun’s world-class expertise in the field of small RNAs was particularly relevant to this ISEV audience. The winner of numerous prestigious science awards throughout his career, Dr. Ruvkun most recently was named a recipient of the 2015 “Breakthrough Prize in Life Sciences” (shared with Dr. Victor Ambros) for “the discovery of a new world of genetic regulation by microRNAs, a class of tiny RNA molecules that inhibit translation or destabilize complementary mRNA targets.” Dr. Ruvkun was warmly introduced to the crowd by brief remarks from Dr. Ken Witwer, Dr. Andrew Hill, and Dr.

Session on Extracellular Vesicles (Including Exosomes) As Diagnostics and Prognostics Highlights Early Morning Events on Final Day of International Society for Extracellular Vesicles (ISEV) 2015 Annual Meeting

The final day of the International Society for Extracellular Vesicles (ISEV) (http://www.isevmeeting.org/) 2015 Annual Meeting in Washington, DC, kicked off with three of the newly-added and highly popular “Meet the Experts” sessions in which world-class experts in a particular area give brief presentations and then interact extensively with the audience in a Q & A session. One of these Sunday sessions was entitled “EVs As Diagnostics and Prognostics,” and was chaired by Fred Hochberg (photo), M.D., a world-renowned expert on glioblastoma, Associate Professor of Neurology at Harvard Medical School, and Attending Neurologist at Massachusetts General Hospital. The two speakers were Clark Chen, M.D., Ph.D., a neurosurgeon/researcher who is the Chief of Stereotactic and Radiosurgery and Director of Medical Education at the University of California, San Diego (UCSD); and Lorraine O’Driscoll, Ph.D., who is Director of Research and Associate Professor of Pharmacology, School of Pharmacy & Pharmaceutical Sciences, at Trinity College Dublin in Ireland. In his brief introduction, Dr. Hochberg emphasized the significance of identifying biomarkers for brain tumors, noting that there are currently four known types of glioblastoma, but it would be “hugely valuable” to have biomarkers that would allow physicians to know the specific subtype as quickly as possible in the disease course. He then introduced Dr. Chen, who he said had a particularly beneficial dual expertise in that he was both a neurosurgeon and a research scientist. The title of Dr. Chen’s brief talk was “Promises and Pitfalls of EVs As a Glioblastoma Liquid Biopsy.” Dr. Chen began by describing the rapid lethality of glioblastoma (GB) and the “opacity of the disease.” Presently, there is no treatment for GB and it is generally fatal within 14 months.

April 25th

Staggering Evolutionary Breadth of Exosomes Is a Theme of Saturday’s Session of ISEV 2015 Annual Meeting in DC

Saturday’s session of the 2015 Annual Meeting of the International Society for Extracellular Vesicles (ISEV) (http://www.isevmeeting.org/), April 23-26 in Washington, DC, opened with three early-morning “Meet the Experts” sessions. These highly valuable sessions offer any of the 800-plus meeting attendees the opportunity to both hear the background and latest news in a particular research area, as delivered by world leaders in that area, but then also to ask questions of these experts. These sessions typically provide a tremendous source of information exchange on key advancing areas in exosome research. One of the three sessions was entitled “Bacterial and Parasite EVs,” and offered exciting information from two of the world leaders in such studies. After a brief introduction by Dr. Pamela Wearsch, herself an expert in Mycobacterium tuberculosis, Dr. Yong Song Gho, a professor at POSTECH, Korea, editor-in-chief of the ISEV’s highly successful, three-year-old Journal of Extracellular Vesicles (JEV), and a 15-year veteran of studying exosomes in bacteria stepped to the microphone to describe some of his seminal work in this area. Dr. Gho first described work done by others in the 1960s to identify what were then called outer membrane vesicles (OMVs) that were produced and released by gram(-) bacteria. After their initial discovery, these OMVs were found everywhere there were gram(-) bacteria and that is essentially everywhere. With regard to the function(s) of the OMVs, there were suggestions that they aided bacterial survival, that they played a role in nutrient sensing, that they might modulate the immune response of the host, and that they might also influence the ABC transporter. Dr.

April 24th

Xandra Breakefield Plenary Address and Special Achievement Award Highlight Friday Session of International Society for Extracellular Vesicles (ISEV) 2015 Annual Meeting in DC

Xandra O. Breakefield (photo), Ph.D., of Mass General Hospital and Harvard University, and a world-leading authority on primary brain tumors, as well as exosomes, presented the Friday morning plenary address to a packed ISEV audience and she did not disappoint. This was the second day of the 2015 annual meeting of the International Society for Extracellular Vesicles (ISEV) (http://www.isevmeeting.org/) being held in Washington, DC, April 23-26. The title of Dr. Breakefield’s presentation was “The Evil Little Things about Cancer EVs As Infiltrators and Informants,” and it was extraordinarily illuminating about both the history of brain cancer research and the emergence of exosomes and/or extracellular vesicles (EVs) as perhaps major players in these grievous maladies. Her talk was briefly preceded by some organizational remarks from Dr. Ken Witwer, chair of the local organizing committee for the meeting, and then some short personal remarks from Dr. Breakefield’s long-time colleague Dr. Fred Hochberg, a prominent neurologist at MGH and Harvard. Dr. Hochberg highlighted Dr. Breakefield’s very special perspective that she can bring to her research as she is a professor in both the Clinical Neurology Department and the Clinical Radiology Department and has spent approximately 20 years focused on clinical medical problems and has an intimate familiarity with medical tools that could be used to examine possible molecular underpinnings of primary brain tumors. With her unusual background, she can bring to bear a remarkable synergy of molecular neuropathology, molecular genetics, and clinical familiarity on the difficult problems she confronts. Dr. Hochberg added that Dr.

April 23rd

Dawn ISEV Satellite Meeting Focuses on HIV and EVs

An early morning satellite meeting on “HIV, NeuroAids, Drug Abuse, and EVs” preceded the official opening of the fourth annual International Society for Extracellular Vesicles (ISEV) meeting in Washington, DC, later in the morning on Thursday, April 23. The general theme was that retroviruses and EVs share many characteristics. And many suggest that, indeed, retroviruses can perhaps be viewed as a type of EV. Despite considerable progress against HIV disease since the discovery of HIV in the 1980s, numerous challenges remain, for example, predicting, diagnosing, and treating the HIV-associated neurocognitive disorders (HAND, including NeuroAIDS). This symposium examined the complex interplay between HIV, host EVs, disease, and drugs of abuse, and was briefly introduced by Dr. Kenneth Witwer, who works in the HIV/exosome area at Johns Hopkins and is chair of the local organizing committee. One of the session speakers was Dr. Norman Haughey, also of Johns Hopkins, and he described his group’s work demonstrating that brain-derived exosomes regulate the peripheral nervous system response to brain injury. In particular, he showed how exosomes from the brain interact with the liver to stimulate the production of neutrophils that travel to the site of injury in the brain. Other session speakers included Dr. Jeymohan Joseph, Chief of HIV Neuropathogenesis at the NIMH, who described “NIMH Priorities in NeuroAids and Exosome Research;” Dr. John Satterlee, Program Director for Epigenetics, Model Organism Genetics & Functional Genomics, NIDA, who spoke on “Extracellular Vesicles: NIDA and the Common Fund Extracellular RNA Communication Program;” Dr. Vincent C. Bond, Acting Chair of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, who spoke on “Cytokines Associated with Exosomes in HIV-infected Individuals;” Dr.

NIH Director Francis Collins & 2013 Nobelist James Rothman Kick Off 2015 Annual International Society for Extracellular Vesicles (ISEV) Meeting in Washington, DC

The 2015 annual meeting of the International Society for Extracellular Vesicles (ISEV) (http://www.isevmeeting.org/) got off to a stunning start on Thursday morning (April 23) with back-to-back plenary presentations by 2013 Nobel Laureate James Rothman, Ph.D., from Yale University, and by NIH Director Francis Collins (photo), M.D., Ph.D., addressing an overflow crowd of more than 800 attendees at this, the largest-ever ISEV annual meeting. These two phenomenal speakers and scientists were followed directly by a 30-minute round-table discussion among the two speakers, Dr. Jan Lötvall, President of the ISEV, Dr. Xandra Breakefield of Harvard University, and Dr. Alan Sachs, the CSO at Thermo-Fischer Scientific. Dr. Rothman was the first to speak after brief introductions by Dr. Ken Witwer of Johns Hopkins, chair of the local organizing committee for the meeting, and Dr. Lötvall. Dr. Witwer was quick to thank all the meeting sponsors and especially to highlight the support that had been provided by both the NIH and the NSF, which supported the attendance of over 40 young investigators. Dr. Lötvall briefly summarized the history of the ISEV from an initial meeting in Canada in 2005 that was attended by ~20 people to a 200-person over-subscribed meeting in Paris in 2011, and finally to today in Washinton, DC, where official registration approached 800 and represented 60% growth over that for the meeting held in Sweden in 2012. Dr. Lötvall also highlighted the immense success that has already been achieved by the ISEV’s Journal of Extracellular Vesicles in its brief three years of existence. It is doing “amazingly well,” Dr. Lötvall noted, as journal editors await assignment of an impact factor. After these brief opening remarks, Dr.

April 22nd

Exosome Education Blooms in Washington, DC

The 2015 Annual Meeting of the International Society for Extracellular Vesicles (ISEV) (http://www.isevmeeting.org/), with a special focus on exosomes, is being held this year in Washington, D.C., and will run from Thursday, April 23, through Sunday, April 26. The official meeting will be kicked off with plenary session addresses by NIH Director Francis Collins, M.D., Ph.D., and 2013 Nobel Laureate James Rothman, Ph.D., on Thursday morning. But before the official opening, the ISEV typically holds an Education Day, particularly for graduate students and those relatively new to the field, in order to bring them up to date on the history and also the latest developments in this fascinating fast-moving-field with so many major implications for clinical and myriad other biological applications. This year’s Education Day was organized jointly by Dr. Ken Witwer for the ISEV and Dr. Christopher Austen, Director of the NIH National Center for Advancing Translational Sciences, and was co-hosted by the ISEV and the NIH Extracellular RNA Communication Consortium (ERCC). The event was a huge success with approximately 400-500 attendees from all over the world completely filling the amphitheater for the entire day to hear many of the major leaders in this exploding field describing exosome history, recent advances, and also critical needs for increased standardization in work done to isolate and characterize exosomes. Included among the many fascinating talks was one by Dr. Yong Song Gho, from Pohang University in South Korea, a world leader on the cargo loading of vesicles, who spoke on the potential role of extracellular RNA (exRNA) in extracellular vesicle (EV)-mediated intercellular communication networks.

April 20th

Bitter Taste Sensitivity Regulated by Immune System Protein TNF; Finding May Help Explain Reduced Food Intake During Illness

New research from the Monell Chemical Senses Center in Philadelphia reveals that tumor necrosis factor (TNF), an immune system regulatory protein that promotes inflammation, also helps regulate sensitivity to bitter taste. The finding may provide a mechanism to explain the taste system abnormalities and decreased food intake that can be associated with infections, autoimmune disorders, and chronic inflammatory diseases. In addition to its role in mediating inflammation, TNF has been implicated in the progression of varied diseases ranging from Alzheimer's disease to cancer. "Reduced food intake and associated malnutrition is a significant concern that affects the long-term prognosis of many people who are very ill," said senior author Hong Wang, Ph.D., a molecular biologist at Monell. "Our findings reveal that bitter taste is regulated by the immune system. Specifically, TNF may make sick people more sensitive to bitterness so that foods taste more bitter and less appetizing." Dr. Wang's research focuses on interactions between the taste and immune systems, with the goal of identifying how taste cell function changes in disease states. As part of this effort, previous research from her laboratory had demonstrated that taste buds contain several immune system proteins, including TNF. Because TNF is known to suppress food intake, the current study asked whether TNF affects food intake via the taste system. The findings were published online on April 21, 2015 in the journal Brain, Behavior, and Immunity. To examine whether TNF helps regulate taste responses, the researchers first compared taste responses of normal mice to those of mice engineered to be lacking the gene for TNF (TNF knockout mice).

Genetic Variance in VNN-1 Network Underlies Poor Response to Common Corticosteroid Asthma Medications; Finding May Lay Groundwork for Helping Difficult-to-Treat Children

Researchers have identified a biological basis for asthmatic children who do not respond well to corticosteroid treatment, currently the most effective treatment for chronic asthma and acute asthma attack. Conducted at Cincinnati Children's Hospital Medical Center, the study also identifies a genetic pathway that could open the possibility of new therapies for difficult-to-treat patients. The findings are reported online on April 21, 2015 in The Journal of Allergy and Clinical Immunology, published by the American Academy of Allergy Asthma and Immunology. The article is titled “Vanin-1 Expression and Methylation Discriminate Pediatric Asthma Corticosteroid Treatment Response.” The researchers performed genome-wide analysis of nasal epithelial cells collected from children experiencing acute asthma exacerbation. They compared genetic expression and medical responses in children who responded well to corticosteroids therapy to those who did not. "Genome-wide analysis allowed us to identify a gene, VNN-1, whose expression discriminated between good and poor responders to systemic corticosteroid treatment," said Gurjit Khurana Hershey, M.D., Ph.D., senior author and director of Asthma Research at Cincinnati Children's. "This may serve as a clinically useful biomarker to identify a subset of difficult-to-treat asthmatic children, and targeting the VNN-1 pathway may be useful as a therapeutic strategy." Asthma affects close to 26 million people in the United States, 7 million of them children. Although people suffering from asthma share similar clinical symptoms, it is triggered by multiple genetic and environmental factors.