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Archive - 2014

November 13th

Scientists Discover Additional Properties of S. pneumoniae That Cause Conjunctivitis

Scientists from Massachusetts Eye and Ear/Harvard Medical School Department of Ophthalmology have used the power of new genomic technology to discover that particular microbes that commonly infect the eye have special, previously unknown properties. These properties are predicted to allow the bacterium --Streptococcus pneumoniae -- to specifically stick to the surface of the eye, grow, and cause damage and inflammation. Researchers are now using this information to develop new ways to treat and prevent infections with this bacterium, which is becoming increasingly resistant to antibiotics. Their findings were published in the current issue of Nature Communications in an article entitled, “"Unencapsulated Streptococcus pneumoniae from Conjunctivitis Encode Variant Traits and Belong to a Distinct Phylogenetic Cluster." S. pneumoniae is a leading cause of infection and is responsible for diseases ranging from infection of the lungs, pneumonia, to infection of the brain, to infection of the surface of the eye, known as conjunctivitis. Although infection of the eye can usually be safely treated, S. pneumoniae infection is a leading cause of illness and death worldwide. According to Massachusetts Eye and Ear researcher Dr. Michael S. Gilmore, Sir William Osler Professor of Ophthalmology, Harvard Medical School, an effective vaccine is available that helps prevent many of the most severe types of infection. "I believe it is especially important for children and the elderly to be vaccinated. The vaccine causes the body to react to a slimy coating on the bacterial surface called a "capsule." The capsule allows S. pneumoniae to escape from white blood cells that try to eliminate it, and S. pneumoniae goes on to cause lung and other infections." However, the strains of S.

Two Mutations Linked to Ewing Sarcoma Subtype with Poor Prognosis; New Combination Therapy May Be Effective

An international collaboration has identified frequent mutations in two genes that often occur together in Ewing sarcoma (ES) and that define a subtype of the cancer associated with reduced survival. The research, conducted by the St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project and the Institut Curie-Inserm through the International Cancer Genome Consortium, appears in the November 2014 issue of Cancer Discovery. Mutations in the genes STAG2 and TP53 have previously been linked to ES. This is the first study, however, to show that patients whose tumors carry alterations in both genes are less likely to survive than are patients without the changes. The discovery stems from the most comprehensive analysis yet of the genetic makeup of ES, a cancer of the bone and soft tissue that primarily strikes children and adolescents. The findings come as St. Jude finalizes plans for clinical trials of an ES combination therapy. A recent St. Jude study showed that the combination therapy was effective in mice with ES that included both mutations. The agents work by damaging DNA or interfering with cellular repair mechanisms. "The current study used whole genome sequencing to define the most comprehensive landscape yet of the genetic alterations that contribute to the growth and recurrence of Ewing sarcoma," said Jinghui Zhang, Ph.D., a member of the St. Jude Department of Computational Biology. Dr. Zhang and Olivier Delattre, M.D., Ph.D., head of the genetic and biology of pediatric cancer group of Institut Curie, Paris, are the study's corresponding authors. "With the combined expertise of St. Jude and Institut Curie, we were able to identify a subtype with a dismal prognosis based on a tumor's genetic profile.

November 11th

Next-Gen Melanoma Drug, TAK-733, Excels in Lab Tests

A University of Colorado (CU) Cancer Center study published online on November 5, 2014 in Molecular Cancer Therapeutics reports anti-cancer activity in 10 of 11 patient tumor samples grown in mice and treated with the experimental drug TAK-733 (image), a small molecule inhibitor of MEK1/2. While the drug is conceived as a second-generation inhibitor in patients harboring the BRAF mutation, the study shows drug activity in melanoma models regardless of BRAF mutation status. Treated tumors shrunk up to 100 percent. “The importance of this molecule is that it’s a next-generation and highly potent inhibitor of a known melanoma pathway. It was highly effective against melanoma and the method of our study – using patient-derived tumor samples grown in mice – makes us especially optimistic that we should see similar results in the human disease,” says John Tentler, Ph.D., investigator at the CU Cancer Center, associate professor at the CU School of Medicine, and one of the paper’s lead authors. Between fifty and sixty percent of human melanomas have an activating mutation in the gene BRAF. According to National Cancer Institute statistics, approximately 1 million people in the United States live with melanoma at any given time. In 2011, the U.S. Food and Drug Administration approved the drug vemurafenib to treat BRAF-mutant melanoma. But while response rates to vemurafenib are in the range of 80 percent for patients with the BRAF mutation, the duration of response is frequently limited to between 2 and 18 months. “We’re learning how to use existing drugs better, for example RAF along with MEK inhibitors to block both mutations and thus a common mechanism of resistance.

November 7th

Bats Identified As Hosts of Deadly Bartonella mayotimonensis

Modern sequencing techniques have shown that bats can carry a bacterial species previously been shown to cause deadly human infections in the USA. When the research group of Dr. Arto Pulliainen at the Department of Biosciences, University of Helsinki, Finland, analyzed an array of bat samples from Finland and the UK, one class of identified bacteria turned out to be exceptionally significant. Multilocus sequence analyses of clonal bat Bartonella isolates demonstrated that bats carry Bartonella mayotimonensis. This species has previously been shown to cause deadly human infections in the USA. “We have barely scratched the surface of bat pathogens. Our group and our collaborators are currently focusing on pathogen hunting, environmental toxicology, and bat immune responses. We have also identified a novel class of microbial toxins via our Bartonella studies and we are going to continue that line of research, too,” says Dr. Pulliainen. There are more than 1,100 species of bats on Earth. The numbers of bats are estimated to outnumber every other group of mammals. "Bats are also highly mobile and long-lived, so they are ideal as pathogen reservoirs. A plethora of pathogenic viruses such as Ebola are known to colonize bats," Dr. Pulliainen says. On the other hand, humans are extremely dependent on bats. Bats play a vital role in natural ecosystems. They pollinate flowers, disperse seeds, and eat pests that damage forests and crops. They also play an important role in arthropod suppression. So what to do when, for example, you have to move out a bat that has accidentally flown into your apartment? "Use thick leather gloves when carrying the bat out.

November 6th

Phase III Trial Results for Afamelanotide Treatment of Erythropoietic Protoporphyria (EPP) or “Popcorn Ichthyosis”

On Saturday, October 18, on the opening evening of the American Society of Human Genetics (ASHG) 2014 annual meeting in San Diego, California, Robert J. Desnick, M.D., Ph.D., the Dean for Genetics and Genomics at the Mt. Sinai School of Medicine, in New York City, had the pleasure of reporting the largely positive results of the phase III clinical trials of the 16 mg subcutaneous bioresorbable implants of afamelanotide for the treatment of the excruciatingly painful, extremely rare, autosomal recessive skin disease known as erythropoietic protoprhyria (EPP), or popularly as “popcorn ichthyosis.” The skin of patients with this genetic condition is severely sensitive to light (which is phototoxic) and the result is intolerable pain, swelling, and scarring, usually of the exposed areas such as the face, hands, and feet. The pain experienced and expressed by EPP patients when their skin is exposed to light is reported as intolerable. Dr. Desnick explained that there is presently no effective treatment except for avoiding the sun and patients are called “shadow jumpers.” EPP is characterized by abnormally elevated levels of protoporphyrin IX in erythrocytes and plasma, and by sensitivity to visible light that is usually noticed in early childhood and occurs throughout life. EPP can result either from mutations of the ferrochelatase gene (FECH), or less commonly of the delta-aminolevulinic acid synthase-2 gene (ALAS2). When EPP is due to an ALAS2 mutation it is termed X-linked protoporphyria (XLP), because that gene is found on the X chromosome.

November 4th

ASHG Honors Gonçalo R. Abecasis and Mark J. Daly with Curt Stern Early-Career Geneticists Award at ASHG 2014 Annual Meeting

The American Society of Human Genetics (ASHG) 2014 has named Gonçalo R. Abecasis, D.Phil., Felix Moore Collegiate Professor of Biostatistics at the University of Michigan School of Public Health (U-M SPH); and Mark J. Daly, Ph.D, Associate Professor of Medicine and Chief of the Analytic and Translational Genetics Unit at Massachusetts General Hospital (MGH)/Harvard Medical School and Senior Associate Member of the Broad Institute, as the 2014 recipients of the Curt Stern Award. This annual award, named for the late pioneering geneticist Curt Stern, Ph.D., recognizes genetics and genomics researchers who have made significant scientific contributions during the past decade. ASHG will present the award, which will include a crystal plaque and $5,000 cash prize to each awardee, on Monday, October 20, during the organization’s 64th Annual Meeting in San Diego. Dr. Abecasis has developed statistical and mathematical methods for the analysis of genetic data that have evolved into standard tools in human genetics. In an era of exponential growth in genetic data, his software helps geneticists analyze studies of families and unrelated individuals, characterize variation among genomes, study connections between genetic variation and human disease, and integrate information across gene-mapping studies. He has also led scientific consortia studying a variety of human traits, such as age-related macular degeneration, heart disease, and metabolic disease. Dr. Abecasis is currently deploying next-generation sequencing technology to study the genomes of thousands of people, with the aim of better understanding genetic variation and human disease biology. In 2008, Dr. Abecasis received the U-M SPH Excellence in Research Award and in 2013, he received the Overton Prize from the International Society for Computational Biology.

Physician-Geneticist Stuart H. Orkin Receives Pristigious Allan Award Award at ASHG 2014 Annual Meeting

The American Society of Human Genetics (ASHG) has named Stuart H. Orkin, M.D., David G. Nathan Professor of Pediatrics at Harvard Medical School, Chairman of the Department of Pediatric Oncology at Dana-Farber Cancer Institute, Associate Chief of Hematology/Oncology at Boston Children’s Hospital and Investigator of the Howard Hughes Medical Institute at Boston Children’s Hospital, as the 2014 recipient of the annual William Allan Award. The Allan Award, which recognizes a scientist for substantial and far-reaching scientific contributions to human genetics, was established in 1961 in memory of William Allan, M.D. (1881-1943), one of the first American physicians to conduct extensive research on human genetics and hereditary diseases. Dr. Orkin received his award, which included an engraved medal and $10,000 monetary prize, on Monday, October 20, 2014, during the ASHG’s 64th Annual Meeting in San Diego. He will present his William Allan Award address immediately thereafter. Dr. Orkin has pioneered research into the genetics behind blood diseases, including identifying the primary mutations (genetic changes) that cause them, defining factors that regulate how these mutations are expressed in blood cells, and applying their findings to medicine. In the late 1970s and early 1980s, Dr. Orkin and colleagues comprehensively defined mutations that lead to the thalassemias, a collection of inherited conditions in which the body produces too little of the oxygen-carrying molecule hemoglobin, which leads to anemia. In the mid-1980s, Dr. Orkin’s laboratory was the first to successfully clone a gene causing a disease (chronic granulomatous disease) without already knowing the protein coded for by the gene. Their approach to mapping mutations has since been used in similar studies of other genetic disorders. More recently, Dr.

ASHG President Cythia Morton, Ph.D., Welcomes Over 6,000 Attendees to San Diego 2014

The following is ASHG President Cytnia Morton’s, Ph.D., welcome to the over 6,000 attendees at the our 2014 ASHG Annual Meeting in San Diego on Friday, October 17, 2014. Dr.Morton is also Willliam Lambert Richardson Professore of Obstetrics, Gynecology, and Reproductive Biology and Professor of Pathology, Harvard Medical School; and Director of Cytogenetics, Brigham and Women’s Hospital. “San Diego is a terrific city in which we have met on several previous occasions and where we have enjoyed our visits together immensely, Dr. Morton began. The theme I have chosen for this meeting is “The Time of Our Lives.” I have had the good fortune over the past 35 years to have a career as a human and medical geneticist, and I can assure you that in every one of those years I have witnessed important discoveries. Never before, however, has it been so clear that the study of the human genome will impact human health and medicine in such a profound way. With that perspective, it is a moment of great privilege and responsibility, and the path we take now will be a legacy for humankind. It is surely “The Time of Our Lives” as human geneticists. Our annual meeting is a wonderful reunion of geneticists from across the lifespan and from around the globe--from those who are the founders of our discipline to the trainees who will become our future leaders. Here we embrace old friends and make new ones, we celebrate remarkable accomplishments of colleagues, and we witness progress not imagined only a few short years ago. We work hard and we play hard, and we have “The Time of Our Lives”.

October 29th

Scientist-of-the-Year Award for Duchenne Muscular Dystrophy Research

The School of Biological Sciences at Royal Holloway, University of London, has been recognized with a national award for its world-class research in the development of novel therapies for rare diseases such as Duchenne muscular dystrophy (DMD). Professor George Dickson, from the School of Biological Sciences and Chair of Molecular Cell Biology, received the Muscular Dystrophy Campaign’s “Scientist of the Year” award from TV presenter Sue Barker (see photo) at the DMD Campaign’s annual conference held in Coventry, UK, on October 18, 2014. Professor Dickson commented: “This is a really nice recognition of the hard work and dedication of our research team, and of past colleagues. I thank my lucky stars to have such a talented team of brilliant, dedicated people, and such a tremendous and supportive research environment in the School and the College.” Professor Dickson has dedicated his career to studying neuromuscular disease and muscle cell biology, including the first cloning of an intact dystrophin gene, the discovery of the role of cell adhesion molecules in muscle stem cell fusion, the first identification of utrophin, and the first description of exon skipping in Duchenne muscular dystrophy (DMD). He has also conducted notable research into gene therapy for atherosclerosis, and genetic vaccination against HIV/AIDS.

Tumor-Derived Exosomes Aid Breast Cancer Progression

Exosomes--tiny, virus-sized particles released by cancer cells (and by virtually all cells in the body)-- can bioengineer micro-RNA (miRNA) molecules resulting in tumor growth. They do so with the help of proteins, such as one named Dicer. New research from The University of Texas MD Anderson Cancer Center suggests that Dicer may also serve as a biomarker for breast cancer and possibly open up new avenues for diagnosis and treatment. Results from the investigation were published online on October 23, 2014 in Cancer Cell. "Exosomes derived from cells and blood serum of patients with breast cancer, have been shown to initiate tumor growth in non-tumor-forming cells when Dicer and other proteins associated with the development of miRNAs are present," said Raghu Kalluri, M.D., Ph.D., chair of the department of cancer biology at MD Anderson. "These findings offer opportunities for the development of exosomes-based biomarkers and shed insight into the mechanisms of how cancer spreads." Exosomes are small vesicles consisting of DNA, RNA, and proteins enclosed in membranes made up of two lipid layers. They perform specialized functions such as coagulation, intercellular signaling, and cell "waste management." They are shed into bodily fluids forming a source of disease-specific nucleic acids and proteins. Increasingly, exosomes are studied for their potential as both indicators of disease, and as a prospective new treatment approach. Exosomes typically contain a cellular stew of smaller components including proteins, messenger RNA (mRNA), and miRNAs. Dr. Kalluri's team reported that breast-cancer-associated exosomes contain specific miRNAs associated with a multi-protein complex known as RNA-induced silencing complex (RISC).