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Archive - May 12, 2017

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Invasive Lung Cancer Cells Display Symbiosis of “Leader” and “Follower” Cells

When cancer cells split off from a tumor to seed deadly metastases, they are thought to travel as clusters or packs, a phenomenon known as collective invasion. The members of an invasive pack are not all alike, scientists at Winship Cancer Institute of Emory University have learned. Lung cancer cells making up an invasive pack have specialized roles as leaders and followers, which depend on each other for mobility and survival, the scientists reported online on May 12, 2017 in Nature Communications. The open-access article is titled “Image-Guided Genomics of Phenotypically Heterogeneous Populations Reveals Vascular Signaling During Symbiotic Collective Cancer Invasion.” The differences between leaders and followers -- and their interdependence -- could be keys for future treatments aimed at impairing or preventing cancer metastasis, says senior author Adam Marcus, PhD, Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute and Emory University School of Medicine. "We're finding that leader and follower cells have a symbiotic relationship and depend on each for survival and invasion," he says. "Because metastatic invasion is the deadliest aspect of cancer, our goal is to find agents that disrupt that symbiotic relationship." Dr. Marcus and former graduate student Jessica Konen, PhD, began by observing how a mass of lung cancer cells behaves when embedded in a 3-D protein gel. The cells generally stick together, but occasionally, a few cells extend out of the mass like tentacles, with the leader cell at the tip. "We saw that when the leader cell became detached or died unexpectedly, the followers could no longer move," says Dr. Konen, now a postdoctoral fellow at MD Anderson.

Single-Cell RNA Sequencing Used in Tracking Maturation of Olfactory Stem Cells

Adult stem cells have the ability to transform into many types of cells, but tracing the path individual stem cells follow as they mature and identifying the molecules that trigger these fateful decisions are difficult in a living animal. University of California, Berkeley, neuroscientists have now combined new techniques for sequencing the RNA in single cells with detailed statistical analysis to more easily track individual stem cells in the nose, uncovering clues that someday could help restore smell to those who have lost it. The results are published this week in the journal Cell Stem Cell. The article is titled “Deconstructing Olfactory Stem Cell Trajectories at Single-Cell Resolution.” "A stem cell's job is twofold: to replace or recreate mature cells that are lost over time, both through normal aging and after injury, and to replace themselves so that the process can continue over the life of the animal," said senior author John Ngai, PhD, the Coates Family Professor of Neuroscience and a member of UC Berkeley's Helen Wills Neuroscience Institute and the Berkeley Stem Cell Center. "We are getting closer to understanding how mature sensory neurons are generated from olfactory stem cells, an understanding that's key for an eventual stem cell therapy to restore function." Dr. Ngai noted that perhaps one-quarter of all people over the age of 50 have some loss of smell, yet doctors have little understanding why, and no treatments for most cases. There's not even a standardized test for loss of smell, as there is for vision or hearing loss, in spite of widespread reports of suffering by patients who have lost their sense of smell. "Some cases of anosmia -- the loss of the sense of smell -- are due to traumatic injury, and there is generally not a whole lot you can do about that," he said.

Cryo-EM Study Reveals Structural Advantage for Use of C-Type Adenovirus in Gene Therapy

In their quest to replicate themselves, viruses have become awfully good at tricking human cells into pumping out viral proteins. That's why scientists have been working to use viruses as forces for good: to deliver useful genes to human cells and help patients who lack important proteins or enzymes. A team of researchers led by Associate Professor Vijay Reddy at The Scripps Research Institute (TSRI) has now uncovered the structural details that make one virus a better tool for future therapies than its closely related "cousin." As Dr. Reddy and his colleagues reported in the May 10, 2017 issue of Science Advances, the structure of a less prevalent species D adenovirus may work well as a gene-delivery vector because its structure doesn't let it get spirited away to the liver, minimizing liver toxicity. The Reddy lab's study is the first to show the structural details on species D's surface that set it apart from another common subtype of adenovirus, called species C, which does travel to the liver. "Greater understanding of the structures of adenoviruses from different species will help generate better gene therapies and/or vaccine vectors," said Reddy. The Science article is titled “Cryo-EM Structure of Human Adenovirus D26 Reveals the Conservation of Structural Organization Among Human Adenoviruses.” Using an imaging technique called cryo-electron microscopy, the researchers discovered that while these two species of adenoviruses share the same shell-like core, they have different surface structures, which Dr. Reddy called "decorations" or "loops." These loops are key to a virus's behavior. They determine which receptors on human cells the virus can bind to. For species C adenoviruses, specific loops help the virus attach to blood coagulation factors (adaptor proteins) and get targeted to the human liver.

Researchers Find Key Molecule for Iron Transport That Could Lead to New Therapies for Anemia; Molecule Found Naturally in Japanese Cypress Tree Leaves

Scientists have identified a key molecule that could lead to new therapies for anemia and other iron disorders "Without iron, life itself wouldn't be feasible," says Barry Paw, MD, PhD, a co-senior author of a new report in Science and Associate Professor at Harvard Medical School, Dana Farber Cancer Institute, Brigham and Women’s Hospital, and Boston Children’s Hospital . "Iron transport is very important because of the role it plays in oxygen transport in blood, key metabolic processes and DNA replication." New findings reported in the May 12, 2017 issue of Science by a multi-institutional team, including researchers from University of Illinois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Brigham and Women's Hospital and Northeastern University, could impact a wide range of iron disorders, ranging from iron-deficiency anemia to iron-overload liver disease. The team has discovered that a small molecule found naturally in Japanese cypress tree leaves, hinokitiol, can bypass iron disorders in animals. Dr. Paw, co-senior author on the new Science paper and physician at Dana-Farber/Boston Children's, and members of his lab demonstrated that hinokitiol can successfully reverse iron deficiency and iron overload in zebrafish disease models. As a result, hinokitiol is believed to have significant therapeutic potential. The Science article is titled “Restored Iron Transport by a Small Molecule Promotes Absorption and Hemoglobinization in Animals." Although iron is crucial to many aspects of health, it cannot transport itself without the help of the body's iron-transporting proteins.