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Archive - Oct 2018

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October 17th

EXOSOME NEWS: Fat Cells & Extracellular Vesicles (EVs) They Release May Hold Solutions for Diabetes; “Findings Represent a New Way of Thinking for Researchers Who Study Diabetes, Obesity, and Metabolism”

Researchers have long known that cells in the human body communicate with one another. Now a team of scientists at the University of Texas (UT) Southwestern Medical Center is hacking into this communication network to learn how fat cells talk with other cells and tissues in the body. Dr. Philipp Scherer, a metabolism expert and Director of the Touchstone Center for Diabetes Research at UT Southwestern, is excited about the new findings because they will allow researchers to test new ideas and re-examine old ones. The study, published online on October 4, 2018 in Cell, shows that fat cells communicate with endothelial cells of the blood vessels that course through fat tissue, and potentially with other organs, by secreted packages of information (extracellular vesicles or EVs, often called exosomes). This communication between cells was demonstrated in a number of new mouse models that researchers created. The title of the new article is “An Endothelial-to-Adipocyte Extracellular Vesicle Axis Governed by Metabolic State.” These findings represent a new way of thinking for researchers who study diabetes, obesity, and metabolism. They open an entirely new door to our understanding of how tissues communicate,” said Dr. Clair Crewe, a postdoctoral researcher in the Touchstone Diabetes Center and first author of the study. “Once we understand the communication process, we can potentially shape it to either enhance or reduce the signaling effect.” The study identified a type of vesicle, a membrane-enclosed sphere, released by fat and other cells. Dr. Scherer compares them to the chocolate surrounding a bonbon. The “filling” includes lipids, signaling molecules, and proteins. The timing of their release is regulated by cycles of fasting and feeding. These vesicles travel throughout the body.

Ancient Andean Genomes Show Distinct Adaptations to Farming and Altitude; Findings Presented at ASHG 2018 Annual Meeting

Ancient populations in the Andes mountains of Peru adapted to their high-altitude environment and the introduction of agriculture in ways distinct from other global populations that faced similar circumstances, according to findings presented on October 17 at the American Society of Human Genetics (ASHG) 2018 Annual Meeting in San Diego, California (October 16-20). The ASHG has reported a record attendance of 8,500 at this year’s meeting. John Lindo, PhD, JD, Assistant Professor of Anthropology at Emory University, and a group of international collaborators headed by Anna Di Rienzo, PhD, at the University of Chicago and Mark Aldenderfer, PhD, at the University of California, Merced, set out to use newly available samples of 7,000-year-old DNA from seven whole genomes to study how ancient people in the Andes adapted to their environment. The scientists compared these genomes with 64 modern-day genomes from both highland Andean populations and lowland populations in Chile, in order to identify the genetic adaptations that took place before the arrival of Europeans in the 1500’s. “Contact with Europeans had a devastating impact on South American populations, such as the introduction of disease, war, and social disruption,” explained Dr. Lindo. “By focusing on the period before that, we were able to distinguish environmental adaptations from adaptations that stemmed from historical events.” The scientists found that Andean populations’ genomes adapted to the introduction of agriculture and resulting increase in starch consumption differently from other populations. For example, the genomes of European farming populations show an increased number of copies of the gene coding for amylase, an enzyme in saliva that helps break down starch.

October 17th

Genome Sequencing Found Feasible & Informative for Pediatric Cancer Treatment; Recommendations Reported at ASHG 2018 Annual Meeting; Work Is Part of St. Jude’s “Genomes for Kids” Study

Comprehensive genetic testing of tumors and non-cancerous tissue from pediatric cancer patients is a feasible and clinically useful approach that can guide patient care, according to findings presented on October 17 at the American Society of Human Genetics (ASHG) 2018 Annual Meeting in San Diego, California (October 16-20). The ASHG reports a record attendance of 8,500 for this year's meeting. Presenting author Scott Newman, PhD; Jinghui Zhang, PhD; and Kim Nichols (photo), MD, along with an interdisciplinary team at St. Jude Children’s Research Hospital, studied 253 pediatric oncology patients with a variety of cancers. In 79 percent of cases, there was at least one finding that could help guide care by providing a diagnosis, revealing patient-specific risks, or identifying drug targets. The researchers conducted whole genome sequencing (WGS), whole exome sequencing (WES), and RNA sequencing of the patients’ tumors, as well as WGS and WES of non-cancerous tissue from the same patient. WGS involves sequencing the patient’s complete genome, while WES involves sequencing those portions that are transcribed into mRNA, most of which codes for proteins. This work was part of the “Genomes for Kids” study (G4K), a large effort to understand how best to use genetic data for pediatric cancer diagnosis and treatment. Differing from other studies that require a specific diagnosis to participate, this study had no prerequisite beyond the presence of adequate tumor tissue for testing. “To my knowledge, this is the first study to offer comprehensive sequencing prospectively for all new patients with adequate samples," said Dr. Nichols. She also noted that the diversity of cancers that were tested helped to verify the relationships between genetic variants and disease. Dr.

October 14th

RNA Key (Non-Coding 886) That Unlocks Innate Immunity

RNA has long been the neglected middle child of biomolecules, the go-between from DNA, which encodes the cell's instructions, to proteins, which carry them out. Increasingly, though, researchers are recognizing RNA as a versatile molecule with, possibly, as many functions as proteins have. New research from Emory University, published in the October 12, 2018 issue of the Journal of Biological Chemistry, shows that one such versatile RNA molecule may be a key player in human cells' frontline defenses against viruses. The title of the article is “A Human Cellular Noncoding RNA Activates the Antiviral Protein 2′–5′-Oligoadenylate Synthetase 1,” Dr. Graeme Conn, the biochemistry professor who oversaw the work, studies how RNA is involved in the body's responses to infections. When a human cell senses a virus, it activates a signaling pathway: a protein called OAS (oligoadenylate synthetase) gets turned on and produces a signaling molecule, which in turn activates another protein that both directly defends against the virus as well as activating other parts of the cell's innate immune system. As it turns out, human RNA might play an important role in this pathway, specifically a human RNA molecule called nc886. The "nc" stands for "noncoding," which means this RNA molecule is not carrying instructions for building a protein. It's doing something all on its own. What it's doing, the new JBC paper shows, is turning on OAS, thus setting off the chain of events that destroys viruses. "We saw that (nc886) wasn't just an activator of this pathway, but a very potent activator," said Brenda Calderon, who carried out the research as a graduate student in Dr. Conn's lab. The nc886 molecule can adopt two different shapes, and one of them is much better at activating OAS than the other.

October 10th

NanoView Completes $10 Million Series B Financing Funding to Support Commercialization of ExoView™ System, NanoView’s Complete Exosome Detection and Characterization Platform; Financing Led by Northpond Ventures

On October 10, 2018, NanoView Biosciences, an emerging leader in the field of exosome detection and characterization, announced the closing of a $10 million Series B financing led by Northpond Ventures. Existing investors, including Sands Capital Ventures and PBM Capital Group, participated in the financing round. Proceeds will be used to complete development of the ExoView system, NanoView’s complete exosome detection and characterization platform, and to prepare the product for commercial launch. “Northpond Ventures really understands the need for more accurate, efficient approaches to characterizing exosomes and we are excited to have them join our current investors,” said Jerry Williamson, Chief Executive Officer of NanoView. “With these funds we are well positioned to complete the development of the first applications of our ExoView system. We plan to launch this platform for research markets in early 2019 and then expand into developing tools for clinical markets in the future.” Exosomes are nanoscale extracellular vesicles secreted by most cell types; they represent a communication system between cells. A growing body of research supports the potential of exosomes to diagnose, monitor, and even treat a broad range of diseases. Most currently available methods for analyzing exosomes are cumbersome, expensive, and require large sample volumes that are not readily available. According to NanoView, the ExoView system is an innovative instrument and consumables platform that efficiently and accurately enables complete detection and characterization of extracellular vesicles, including exosomes.

October 10th

Anti-Psychotic Drug May Be Effective Against Triple-Negative Breast Cancer

A commonly used anti-psychotic drug could also be effective against triple-negative breast cancer, the form of the disease that is most difficult to treat, new research has found. The study, led by the University of Bradford in the UK, also showed that the drug, pimozide, has the potential to treat the most common type of lung cancer. Anti-psychotic drugs are known to have anti-cancer properties, with some studies, albeit inconclusive, showing a reduced incidence of cancer amongst people with schizophrenia. The new research, published online on October 9, 2018 in Oncotarget, is the first to identify how one of these drugs acts against triple-negative breast cancer, with the potential to be the first targeted treatment for the disease. Lead researcher, Professor Mohamed El-Tanani (photo) from the University of Bradford, said: "Triple-negative breast cancer has lower survival rates and increased risk of recurrence. It is the only type of breast cancer for which only limited targeted treatments are available. Our research has shown that pimozide could potentially fill this gap. And because this drug is already in clinical use, it could move quickly into clinical trials." The researchers, from the University of Bradford, Queen's University Belfast (Northern Ireland), and the University of Salamanca (Spain), tested pimozide in the laboratory on triple-negative breast cancer cells, non-small cell lung cancer cells, and normal breast cells. They found that, at the highest dosage used, up to 90 per cent of the cancer cells died following treatment with the drug, compared with only 5 per cent of the normal cells. The researchers then tested the drug on mice implanted with triple-negative breast cancer.

Specific Gene Types Driving Higher Frequency of Myeloma Diagnosis in African-Americans Identified By Mayo Clinic Researchers; DNA Sequencing Used to More Accurately Determine Racial Ancestry; Findings May Aid Insight into Best Forms of Therapy

Researchers at the Mayo Clinic in Rochester, Minnesota, have identified three specific gene types that account for a known two-to-three-fold increase in myeloma diagnoses among African-Americans. Researchers also demonstrated the ability to study race and racial admixture more accurately using DNA analysis. The findings were published online on October 10, 2018 in Blood Cancer Journal. The open-access article is titled “Differences in Genomic Abnormalities Among African Individuals with Monoclonal Gammopathies Using Calculated Ancestry.” "Myeloma is a serious blood cancer that occurs two to three times more often in African-Americans than Caucasians," says Vincent Rajkumar(photo), MD. a hematologist at the Mayo Clinic and senior author of the study. "We sought to identifying the mechanisms of this health disparity to help us better understand why myeloma occurs in the first place and provide insight into the best forms of therapy." Dr. Rajkumar and his colleagues studied 881 patients of various racial groups. Researchers found that the higher risk of myeloma known to occur in African-Americans was driven by three specific subtypes of the cancer characterized by the presence of genetic translocations in cancer cells. Translocations are genetic abnormalities in cancer cells caused by the rearrangement of parts between nonhomologous chromosomes. The translocation researchers identified were t(11;14), t(14;16), and (t14;20). "Previous efforts to understand this disparity have relied on self-reported race rather than on genetic ancestry, which may have resulted in bias," explains Dr. Rajkumar. "A major new aspect of this study is that we identified the ancestry of each patient through DNA sequencing, which allowed us to determine ancestry more accurately." Dr.

October 9th

EXOSOME NEWS: Avalon GloboCare Teams with Weill Cornell Medicine to Co-Develop Standardization of cGMP-Grade Exosome Isolation and Application of Tissue-Specific Exosomes

On October 9, 2018, Avalon GloboCare Corp. (OTCQB: AVCO), a leading global developer of cell-based technologies and therapeutics, headquartered in New Jersey, USA, announced that Weill Cornell Medicine has selected its subsidiary Genexosome Technologies’ proprietary exosome isolation system as a key component in the world’s first standardization processing of cGMP-grade exosomes for clinical studies. This co-development program is led by Yen-Michael Hsu, MD, PhD, Director of cGMP Cellular Therapy Facility and Laboratory for Advanced Cellular Engineering at Weill Cornell. This co-development program will focus on two main objectives: (1) standardization of cGMP-grade exosome isolation from human endothelial cells, essential for vascular health and organ regeneration; and (2) identification and isolation of tissue-specific exosomes for liquid biopsy and clinical use. A material transfer agreement will accompany this announcement to facilitate and authorize the use of GenExosome’s isolation system by Weill Cornell. “Identification and isolation of tissue-specific exosomes is considered by many as the “Holy Grail” in this area. This co-development and standardization initiative with Weill Cornell has further enhanced the global recognition, intellectual property, as well as our leading role in this industry sector,” stated Yu Zhou, MD, PhD, Founder and Co-CEO of GenExosome Technologies, Inc. "This strategic co-development endeavor will synergize Genexosome Technologies’ top-rated isolation platform with Weill Cornell’s world-class cGMP cellular therapy/cell-derived product processing facility to accelerate innovative exosome technology development, as well as standardization in clinical-grade exosome bio-production process,” stated David Jin, MD, PhD, CEO and President of Avalon GloboCare Corp.

Two Genes Responsible for Remarkable Difference in Flower Color of Nearby Snapdragons Identified; Islands of Divergence Established by Gene Flow & Multiple Selective Sweeps; Bee Pollination a Key Factor

Snapdragons are charming tall plants that flower in a range of bright colors. In Spain, where snapdragons grow wild, these flower colors show a remarkable pattern: When driving up a road from Barcelona to the Pyrenees, snapdragons of the species Antirrhinum majus bloom in magenta at the beginning of the road, before a population of yellow flowering snapdragons takes over - separated by just a two kilometer c long stretch in which flower colors mix. Such hybrid zones of snapdragons are quite infrequent; only a few others are known. But why don't the snapdragons mix, with yellow and magenta flowers growing together over a wide area? Dr. Nick Barton at the Institute of Science and Technology Austria (IST Austria), together with Dr. David Field, previously a postdoc in Dr. Barton's group and now Assistant Professor at the University of Vienna, collaborated with molecular geneticists at the John Innes Center in Norwich, UK, to investigate the causes of this pattern. In an article published online on October 8, 2018 in PNAS, the scientists report that they identified the genes responsible for flower color difference from DNA sequence data. The open-access article is titled “Selection and Gene Flow Shape Genomic Islands That Control Floral Guides.” "DNA sequencing is becoming cheaper and cheaper. But analyzing sequence data and interpreting the patterns seen is very hard,” Dr. Barton explains. “In this study, we used sequence data from Antirrhinum plants to locate the individual genes that are responsible for the difference in flower color across the hybrid zone." The researchers compared the genome sequences of 50 snapdragons of each color, and measured how much the sequences diverged between magenta and yellow snapdragon populations.

Phenylketonuria Cured in Mouse Model by Adaptation of CRISPR/Cas9 Gene Editing—60% Gene Correction Rate Achieved Employing Base Editor Cytidine Deaminase

Parents of newborns may be familiar with the metabolic disorder phenylketonuria: in Switzerland, all newborn babies are screened for this genetic disease. If a baby is found to have phenylketonuria, he or she requires a special diet so that the amino acid phenylalanine does not accumulate in the body. Excess phenylalanine delays mental and motor development. If left untreated, the children may suffer massive mental disability. The cause of this metabolic disorder is a mutation in a gene that provides the blueprint for the enzyme phenylalanine hydroxylase (Pah). This enzyme, which is produced by the cells of the liver, metabolizes phenylalanine. The disorder is referred to as "autosomal recessive"--the child develops the disease if he or she inherits one mutated Pah gene from the mother and one from the father. There has been no cure for this disorder to date. A team of researchers led by ETH Zurich professor Gerald Schwank has now taken advantage of a method to correct both mutated genes in the liver cells and thus heal the disease. (Editor’s Note: ETH Zurich is a science, technology, engineering, and mathematics university in the city of Zürich, Switzerland.) Dr. Schwank’s team has succeeded, at least in mice. With the help of a CRISPR/Cas9 system extended by one enzyme, the researchers changed the sequence of the DNA building blocks for the Pah corresponding gene in adult mice. The mouse liver cells were subsequently able to produce functioning Pah enzymes, and the mice were healed. The work was reported online on October 8, 2018 in Nature Medicine. The article is titled “Treatment of a Metabolic Liver Disease by In Vivo Genome Base Editing in Adult Mice.” Following are more details on the work.