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Archive - Oct 28, 2011

New Discovery May Bring Lung Regeneration Closer to Reality

Researchers at Weill Cornell Medical College, and colleagues, say they have taken an important step forward in their quest to "turn on" lung regeneration -- an advance that could effectively treat millions of people suffering from respiratory disorders. In the October 28, 2011 issue of Cell, the research team reports that they have uncovered the biochemical signals in mice that trigger generation of new lung alveoli, the numerous, tiny, grape-like sacs within the lung where oxygen exchange takes place. Specifically, the regenerative signals originate from the specialized endothelial cells that line the interior of blood vessels in the lung. While it has long been known that mice can regenerate and expand the capacity of one lung if the other is missing, this study now identifies molecular triggers behind this process, and the researchers believe these findings are relevant to humans. "Several adult human organs have the potential upon injury to regenerate to a degree, and while we can readily monitor the pathways involved in the regeneration of liver and bone marrow, it is much more cumbersome to study the regeneration of other adult organs, such as the lung and heart," says the study's lead investigator, Dr. Shahin Rafii, who is the Arthur B. Belfer Professor of Genetic Medicine and co-director of the Ansary Stem Cell Institute at Weill Cornell Medical College. "It is speculated, but not proven, that humans have the potential to regenerate their lung alveoli until they can't anymore, due to smoking, cancer, or other extensive chronic damage," says Dr. Rafii, who is also an investigator of the Howard Hughes Medical Institute.

Genome Studies Reveal Extensive Copy Number Variation in Leishmania Parasites

Two remarkable discoveries have been revealed by researchers analyzing the genomes of Leishmania parasites. The research results were published in two studies appearing online on October 28, 2011 in Genome Research. First, the scientists found that the DNA sequence of individual strains of each species populations is almost completely identical. It appears that only a small number of genes may cause different symptoms of infection. Second, the parasite's evolutionary development and success may be driven by a genetic abnormality leading to multiple copies of chromosomes that would kill most organisms. This process leads to multiple copies of chromosomes and genes known as copy number variation. These studies increase our understanding of the process of drug resistance in Leishmania. Leishmaniasis is a disfiguring and potentially fatal disease that affects two million people each year. There are four main forms of the disease; ranging from skin lesions (cutaneous leishmaniasis), caused by species that include Leishmania mexicana, to a deadly infection of internal organs (visceral leishmaniasis, also called “black fever”) caused by Leishmania donovani parasites. Leishmania parasites are transmitted by sand flies and are found in 88 countries around the world. Leishmaniasis is poverty-related and typically affects the poorest of the poor: it is associated with malnutrition and displacement. The World Health Organization is committed to eradicating the disease in endemic areas. In the first of the two current studies, the researchers generated a high-quality draft genome of L. donovani using a sample taken from an infected patient in Nepal. The team used this as a reference framework to analyse a further 16 isolates from Nepal and India that had different responses to antibiotic medications.

Genetic Risk Factor Identified for Major Depression

Scientists at the Texas Biomedical Research Institute and Yale University have identified a new target area in the human genome that appears to harbor genes with a major role in the onset of depression. Using the power of Texas Biomed’s AT&T Genomics Computing Center (GCC), the researchers found the region by devising a new method for analyzing thousands of potential risk factors for this complex disease, a process that led them to a new biomarker that may be helpful in identifying people at risk for major depression. “We were searching for things in psychiatric disease that are the equivalent of what cholesterol is to heart disease,” said Dr. John Blangero, director of the GCC and a principal investigator in the study. “We wanted to find things that can be measured in everybody and that can tell you something about risk for major depression.” The study was directed by Dr. Blangero and Dr. David Glahn, of Yale University. It was published online on October 7, 2011 in the journal Biological Psychiatry and supported by the National Institutes of Health. Major depressive disorder is one of the most common and most costly mental illnesses. Studies have estimated that up to 17 percent of Americans will suffer depression at some point in their lives. The disorder has proven to be a tough challenge for geneticists. Despite strong evidence that people can inherit a susceptibility to major depression, years of study have failed to locate any of the key genes that underlie the illness. In this study, the scientists used blood samples from 1,122 people enrolled in the Genetics of Brain Structure and Function Study, a large family study that involves people from 40 extended Mexican American families in the San Antonio area. Dr.

New Oncolytic Virus Shows Promise for Treatment of Brain Cancer

A new, fourth-generation oncolytic virus designed to both kill cancer cells and inhibit blood-vessel growth has shown greater effectiveness than earlier versions when tested in animal models of human brain cancer. Researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) are developing the oncolytic virus as a treatment for glioblastoma, the most common and deadly form of brain cancer (average survival: 15 months after diagnosis). The new oncolytic virus, called 34.5ENVE, improved survival of mice with transplanted human glioblastoma tumors by 50 percent in a majority of cases compared with the previous-generation oncolytic virus. The study was published online on October 25, 2011 in the journal Molecular Therapy. “These findings show the amazing therapeutic efficacy of this new oncolytic virus against four different glioblastoma models in animals,” says cancer researcher Dr. Balveen Kaur, associate professor of neurological surgery, and a member of the OSUCCC – James viral oncology research program. The new oncolytic virus is engineered to replicate in cells that express the protein nestin. First identified as a marker for neuronal stem cells, nestin is also expressed in glioblastoma and other malignancies, including gastrointestinal, pancreatic, prostate, and breast cancer. “We believe that nestin-driven oncolytic viruses will prove valuable for the treatment of many types of cancer,” Dr. Kaur says. The new oncolytic virus also carries a gene to inhibit tumor blood-vessel growth. That gene, called Vstat120, was added to increase the virus’s anti-tumor effectiveness and prolong the virus’s presence within tumors.

Scientists Identify Stem Cell Key to Lung Regeneration

Scientists at A*STAR (Agency for Science, Technology, and Research)’s Genome Institute of Singapore (GIS) and Institute of Molecular Biology (IMB), together with colleagues, have made a breakthrough discovery in the understanding of lung regeneration. Their research showed for the first time that distal airway stem cells (DASCs), a specific type of stem cells in the lungs, are involved in forming new alveoli to replace and repair damaged lung tissue, providing a firm foundation for understanding lung regeneration. The new research was reported in the October 28, 2011 issue of Cell. Lung damage is caused by a wide range of lung diseases including influenza infections and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Influenza infection induces acute respiratory distress syndrome (ARDS) which affects more than 150,000 patients a year in the US, with a death rate of up to 50 percent. COPD is the fifth biggest killer worldwide. The research team took a novel approach in tackling the question of lung regeneration. They cloned adult stem cells taken from three different parts of the lungs - nasal epithelial stem cells (NESCs), tracheal airway stem cells (TASCs), and distal airway stem cells (DASCs). Despite the three types of cells being nearly 99 percent genetically identical, the team made the surprising observation that only DASCs formed alveoli when cloned in vitro. "We are the first researchers to demonstrate that adult stem cells are intrinsically committed and will only differentiate into the specific cell type they originated from. In this case, only DASCs formed alveoli because alveolar cells are found in the distal airways, not in the nasal epithelial or tracheal airway," said Dr Wa Xian, Principal Investigator at IMB.