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Archive - Mar 5, 2017

Study Identifies Common Gene Variants Associated with Gallbladder Cancer; Findings Lead to Clues to Causes for Highly Fatal Disease

By comparing the genetic code of gallbladder cancer patients with those of healthy volunteers at nearly 700,000 different locations in the genome, researchers say they have found several gene variants which may predispose individuals to develop the disease. The findings, published online on March 5, 2017 in The Lancet Oncology, could lead to a better understanding of the causes of this highly fatal condition, which could in turn lead to better treatments for the disease. The work is a collaboration between the Johns Hopkins Bloomberg School of Public Health, the National Cancer Institute and Tata Memorial Cancer Centre in Mumbai, India. The article is titled “"Common Genetic Variation and Risk of Gallbladder Cancer: A Case-Control Genome Wide Association Study.” Although gallbladder cancer is rare in most parts of the world, it is far more common among some ethnic groups, such as Native Americans in North America, and in certain geographic regions, including Central and South America and East and Southeast Asia. The 178,000 new cases diagnosed worldwide each year are centered primarily in these high-risk regions. "Using the latest technologies to look at the causes - notably the genetic underpinnings - of this understudied disease just makes a lot of sense," says study co-leader Nilanjan Chatterjee, Ph.D., Bloomberg Distinguished Professor in the Department of Biostatistics at the Bloomberg School and a Professor of Oncology at the Johns Hopkins Kimmel Cancer Center The gallbladder is a tiny organ in the abdomen that stores bile, the digestive fluid produced by the liver. When gallbladder cancer is discovered early, the chances for survival are good, but most gallbladder cancers are discovered late as it is difficult to diagnose because it often causes no specific symptoms.

Microbiome Diversity Is Influenced by Chance Encounters; Study Finds Role for Randomness in Composition of Gut’s Microbe Populations

Within the human digestive tract, there are trillions of bacteria, and these communities contain hundreds or even thousands of species. The makeup of those populations can vary greatly from one person to another, depending on factors such as diet, environmental exposure, and health history. A new study of the microbe populations of worms offers another factor that may contribute to this variation: chance. MIT researchers found that when they put genetically identical worms into identical environments and fed them the same diet, the worms developed very different populations of bacteria in their gut, depending on which bacteria happened to make it there first. “This study shows that you can have heterogeneity that’s driven by the randomness of the initial colonization event. That’s not to say the heterogeneity between any two individuals has to be driven by that, but it’s a potential source that is often neglected when thinking about this variation,” says Jeff Gore, Ph.D., the Latham Family Career Development Associate Professor of Physics at MIT. Dr. Gore is the senior author of the study, which was published online on March 3, 2017 in PLOS Biology. The paper’s lead author is MIT postdoc Dr. Nicole Vega. The open-access article is titled “Stochastic Assembly Produces Heterogeneous Communities in the Caenorhabditis elegans Intestine.” Variations in the human gut microbiome have been shown to contribute to gastrointestinal disorders such as colitis and Crohn’s disease, and studies suggest that microbiome composition can also influence diabetes, heart disease, and cancer.

Graphene Sheets Capture Cells Efficiently; New Method Could Enable Pinpoint Diagnostics on Individual Blood Cells

A single cell can contain a wealth of information about the health of an individual. Now, a new method developed at MIT and National Chiao Tung University in Taiwan could make it possible to capture and analyze individual cells from a small sample of blood, potentially leading to very low-cost diagnostic systems that could be used almost anywhere. The new system, based on specially treated sheets of graphene oxide, could ultimately lead to a variety of simple devices that could be produced for as little as $5 apiece and perform a variety of sensitive diagnostic tests even in places far from typical medical facilities. The material used in this research is an oxidized version of the two-dimensional form of pure carbon known as graphene, which has been the subject of widespread research for over a decade because of its unique mechanical and electrical characteristics. The key to the new process is heating the graphene oxide at relatively mild temperatures. This low-temperature annealing, as it is known, makes it possible to bond particular compounds to the material's surface. These compounds in turn select and bond with specific molecules of interest, including DNA and proteins, or even whole cells. Once captured, those molecules or cells can then be subjected to a variety of tests. The findings were reported online on January 13, 2017 in the journal ACS Nano in a paper co-authored by Dr. Neelkanth Bardhan, an MIT postdoc, and Priyank Kumar Ph.D.

Epigenetic Enzyme Found Lacking in Some Patients with Crohn's Disease; Mass General Study Reveals Essential Role of SP140 Protein in Innate Immune Function and Intestinal Health

A Massachusetts General Hospital (MGH) research team has found how a variant in an important epigenetic enzyme -- previously associated by population-based genetic studies with Crohn's disease and other immune disorders -- interferes with the action of the innate immune system, potentially upsetting the healthy balance between the microbial population of the gastrointestinal tract and the immune response. In a paper published in Science Immunology, the researchers report findings that SP140 -- an epigenetic reader protein that plays a critical role in determining whether or not target genes are expressed -- is essential to suppressing inappropriate gene expression in macrophages, innate immune cells that are critical to maintaining intestinal balance. "More than 400 enzymes write, read, or erase the epigenome, and mutations in these enzymes are some of the most prevalent perturbations in cancers, prompting rigorous efforts to identify compounds that could inhibit their function and reset gene expression," says Kate Jeffrey, Ph.D., of the MGH Gastrointestinal Unit and the Center for the Study of Inflammatory Bowel Disease, corresponding author of the article published in the March 3, 2017 issue of Science Immunology. The article is titled “Maintenance of Macrophage Transcriptional Programs and Intestinal Homeostasis by Epigenetic Reader SP140.” "Our knowledge of epigenomic enzyme mutations in immune-mediated disease is lagging well behind the cancer field, and our study -- the first to examine the function of SP140 in any detail -- shows how its loss in Crohn's disease triggers intestinal inflammation." SP140 is predominantly expressed in immune cells, and a variant form of the gene has been associated with Crohn's disease, multiple sclerosis, and chronic lymphocytic leukemia.

Award Honors Research on Communication Between Bacteria and Humans

University of Texas (UT) Southwestern Medical Center microbiologist Dr. Neal Alto (photo) has been named a recipient of the 2017 Norman Hackerman Award in Chemical Research for his work on interspecies communication between disease-causing bacteria and the humans they infect. The Welch Foundation, one of the nation’s oldest and largest sources of private funding for basic research in chemistry, presents the $100,000 award annually to honor early-career scientists at Texas institutions who are expanding the frontiers of chemistry. The award is named after Dr. Norman Hackerman, an internationally known chemist and former president of both the University of Texas at Austin and Rice University. Dr. Alto, an Associate Professor of Microbiology, is the sixth UT Southwestern researcher to receive the award since it was first given in 2002. This year marks the first time the award has been presented to two scientists; the other recipient is Dr. Delia J. Milliron of UT Austin for her research on semiconductor nanocrystals. “Dr. Alto’s insights into the intersection between bacteria and our immune defense system have the potential to lead to new approaches to the prevention and treatment of infectious diseases, which remain among the most challenging health problems worldwide,” said Dr. Daniel K. Podolsky, President of UT Southwestern and holder of the Doris and Bryan Wildenthal Distinguished Chair in Medical Science. “Through the application of his expertise in both microbiology and chemistry, we are confident that with the support of this award, Dr. Alto will make significant further advances in this vital area of research, and we are proud to see him honored in this way.” The Alto laboratory studies bacterial toxins that interfere with essential processes of human cells.