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Archive - Apr 2015

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.

April 20th

Discovery of Gene Involved in Determining Melting Point of Cocoa Butter May Have Major Economic Impact; Current Global Cocoa Production Valued at $11.8 Billion; New Specialty Chocolates, Cosmetics, and Pharmaceuticals Envisioned

The discovery of a gene involved in determining the melting point of cocoa butter -- a critical attribute of the substance widely used in foods and pharmaceuticals -- will likely lead to new and improved products, according to researchers in Penn State's College of Agricultural Sciences. The finding by plant geneticists also should lead to new varieties of the cocoa plant that could extend the climate and soil-nutrient range for growing the crop and increase the value of its yield, they said, providing a boost to farmers' incomes in the cocoa-growing regions of the world. Cacao, Theobroma cacao L., is an understory tropical tree domesticated in the Amazon basin and today widely cultivated in West Africa, Central and South America, and Southeast Asia. Around the world, more than five million cocoa farmers -- and more than 40 million people total -- depend on cocoa for their livelihood, according to the World Cocoa Foundation, which puts annual cocoa production worldwide at 3.8 million tons, valued at $11.8 billion. Cacao pods, each containing around 40 seeds, are harvested approximately 20 weeks after pollination. The seeds contain about 50 percent total lipids (cocoa butter), which provides a main raw ingredient for chocolate manufacturing, as well as ingredients for pharmaceutical and cosmetic products. Cocoa butter with altered melting points may find new uses in specialty chocolates, cosmeticsm and pharmaceuticals, said lead researcher Dr. Mark Guiltinan, Professor of Plant Molecular Biology, who has been conducting research on the cacao tree for three decades. For example, a chocolate with a higher or lower melting point would be useful for production of chocolate with specific textures and specialty applications.

Draft Genome for Upland Cotton—Which Accounts for More Than 90% of the World’s Cultivated Cotton and $500 Billion in Economic Impact—Is Established; Should Prove Resource for Engineering Superior Cotton Lines and Fiber Improvement

In a groundbreaking achievement led by an international team that includes Clemson (South Carolina) scientist Dr. Chris Saski, the intricately woven genetic makeup of Upland cotton has been decoded for the first time in the ancient plant's history. Dr. Saski participated in sequencing the genome, which is a crucial stepping-stone toward further advancements of understanding the inner workings of one of the most complex and treasured plants on the planet. The future implications of Dr. Saski's and his colleagues’ research, in the short and long terms, are both financial and holistic. Upland cotton, which accounts for more than 90 percent of cultivated cotton worldwide and has a global economic impact of $500 billion, is the main source of renewable textile fibers. The draft genome sequence, unveiled April 20, 2015 in an online, open-access article in Nature Biotechnology, will provide the know-how to engineer superior lines that will help clothe, feed, and fuel the ever-expanding human population. The Nature Biotechnology article is titled “Sequencing of Allotetraploid Cotton (Gossypium hirsutum L. acc. TM-1) Provides a Resource for Fiber Improvement.” "From the discovery standpoint - having a solid foundation to begin measuring genetic diversity and how the genes are organized - this is a game-changer," said Dr. Saski, Director of Clemson's Genomics and Computational Biology Laboratory. "With a genome map and genetically diverse populations, you can reveal the biology and DNA signature underlying cotton fiber development. Then you can use this information to breed cotton lines with advanced fiber elongation and fiber strength, which are crucial to the industry.

With Systemic Administration in Animal Models, Common Topical Drugs for Athlete’s Foot and Eczema Both Stimulate Body's Own Stem Cells to Replace Brain Cells Lost in Multiple Sclerosis and Enhance Remyelination

A pair of topical medicines already alleviating skin conditions each may prove to have another, even more compelling use: instructing stem cells in the brain to reverse damage caused by multiple sclerosis. Led by researchers at Case Western Reserve School of Medicine, a multi-institutional team used a new discovery approach to identify drugs that could activate mouse and human brain stem cells in the laboratory. The two most potent drugs - one that currently treats athlete's foot (miconazole), and the other (clobetasol), eczema - were capable of stimulating the regeneration of damaged brain cells and reversing paralysis when administered systemically to animal models of multiple sclerosis. The results were published online on Monday, April 20, in Nature. The article is titled “Drug-Based Modulation of Endogenous Stem Cells Promotes Functional Remyelination in Vivo.” "We know that there are stem cells throughout the adult nervous system that are capable of repairing the damage caused by multiple sclerosis, but until now, we had no way to direct them to act," said Paul Tesar, Ph.D., the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics, and Associate Professor in the Department of Genetics & Genome Sciences at the Case Western Reserve School of Medicine. "Our approach was to find drugs that could catalyze the body's own stem cells to replace the cells lost in multiple sclerosis." The findings mark the most promising developments to date in efforts to help the millions of people around the world who suffer from multiple sclerosis. The disease is the most common chronic neurological disorder among young adults, and results from aberrant immune cells destroying the protective coating, called myelin, around nerve cells in the brain and spinal cord.

Possible Cure for Hepatitis B Virus (HBV) Infection; 2 Billion People Infected Worldwide; 400 Million Have Chronic Infections; 780,000 Deaths Annually; Human Clinical Trials Underway in Australia

Australian scientists have found a potential cure for hepatitis B virus (HBV) infections, with a promising new treatment proving 100 per cent successful in eliminating the infection in preclinical models. Australian patients are now the first in the world to have access to the potential treatment - a combination of an antiviral drug and an anti-cancer drug - which is in phase 1/2a clinical trials in Melbourne, Perth, and Adelaide. Scientists from Melbourne's Walter and Eliza Hall Institute developed the combination treatment using birinapant, a drug developed by U.S. biotech company TetraLogic Pharmaceuticals (http://tetralogicpharma.com/) for treating cancer. Hepatitis B is a chronic viral disease that is currently incurable. Dr. Marc Pellegrini (photo), Dr. Greg Ebert, and colleagues at the Institute used their studies of the behavior of hepatitis B virus in infected cells as a basis for the treatment. The research was published online on April 20, 2015 in two papers in PNAS. Dr. Pellegrini said the treatment was successful in curing infections in preclinical models, leading to a human trial that began in December 2014. "We were 100 per cent successful in curing HBV infection in hundreds of tests in preclinical models," Dr. Pellegrini said. "Birinapant enabled the destruction of hepatitis B-infected liver cells while leaving normal cells unharmed. Excitingly, when birinapant was administered in combination with current antiviral drug entecavir, the infection was cleared twice as fast compared with birinapant alone.

AACR ANNUAL MEETING: Gene Signatures (COXEN Model) Can Predict Doxorubicin Response in Canine Osteosarcoma; Similar Approach May Also Prove Useful in Human Cancers

There are two chemotherapies commonly used to treat bone cancer in dogs: doxorubicin and carboplatin. Some dogs respond better to one drug than to the other. But until now, the choice has been left largely to chance. New work by University of Colorado (CU) Cancer Center members at Colorado State University Flint Animal Cancer Center and presented on April 19, 2015 at the American Association for Cancer Research (AACR) Annual Meeting 2015 (April 18-22, 2015, in Philadelphia) demonstrates a gene expression model that predicts canine osteosarcoma response to doxorubicin, potentially allowing veterinary oncologists to better choose which drug to use with their canine patients. The approach is adopted from, and further validates, a model known as COXEN (CO-eXpression gEne aNalysis), developed at the CU Cancer Center by Center Director Dan Theodorescu, M.D., Ph.D., and which is currently in clinical trials to predict the response of human tumors to drugs. "This is a cool thing for us, showing that we can use human models in canine cancer, and hinting that the reverse might also be true: the lessons we learn from canine osteosarcoma may help us better understand the human disease," says Daniel L. Gustafson, Ph.D., CU Cancer Center Investigator and Director for Basic Research at the Flint Animal Cancer Center. The COXEN model depends on the idea that cancer can be defined as the sum of its genetic alterations. Rather than looking at a cancer by its site in the body - say lung cancer or prostate cancer or breast cancer - the COXEN model evaluates a panel of genes known to be important to the development of cancer and uses gene expression to label the cancer with a genetic signature.