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Archive - Mar 2017

March 5th

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.

March 4th

New Book Explores Promise & Peril of Having Children in Age of Genetic Testing & Interventions

“The Gene Machine-- How Genetic Technologies Are Changing the Way We Have Kids—and the Kids We Have” (https://www.amazon.com/Gene-Machine-Technologies-Changing-Kids/dp/037416...) is a new book published on February 28, 2017, and authored by award-winning journalist Bonnie Rochman. The book explores the promise and peril of having children in an age of genetic tests and interventions through the stories of parents and kids, doctors and genetic counselors, all learning to navigate a world overflowing with information and insights. A former health and parenting columnist for Time magazine, Ms. Rochman has also written for The New York Times Magazine, The Wall Street Journal, NBC News, Scientific American, and O, The Oprah Magazine. An excerpt from her new book appears in the March 2017 issue of Scientific American (https://www.scientificamerican.com/article/full-genome-sequencing-for-ne...). Early comments on the book include the following. “An exciting, informative, and lucidly written book about genes and the future"--Siddhartha Mukherjee, Pulitzer Prize-winning, bestselling author of “The Gene and The Emperor of All Maladies.” "Bonnie Rochman has taken a subject that every parent worries about but few understand, and made it accessible, urgent, and humane. The Gene Machine is like a guidebook to the future. It will be invaluable for many families.”--Bruce Feiler, New York Times bestselling author of “The Secrets of Happy Families.” "Bonnie Rochman dives into the turbulent waters of genetic testing and emerges with The Gene Machine, a smart and compassionate account of this ever-advancing science. Her curiosity and compelling narrative will challenge you to consider all the 'what-ifs' of the future of gene sequencing. Go on this journey with her. Take the plunge.

Genome Sequencing Reveals Aspergillus Diversity for Industrial Applications--"The Potential for Applications within the Genus Has Barely Been Touched."

In the world of fungi, Aspergillus is an industrial superstar. Aspergillus niger, for example, has been used for decades to produce citric acid--a compound frequently added to foods and pharmaceuticals --through fermentation at an industrial scale. Other species in this genus play critical roles in biofuel production, and plant and human health. Because the majority of its 350 species have yet to be sequenced and analyzed, researchers are still at the tip of the iceberg when it comes to understanding Aspergillus' full potential and the spectrum of useful compounds these fungi may generate. In a study published February 14, 2017 in the journal Genome Biology, an international team, including researchers at the U.S. Department of Energy Joint Genome Institute (DOE JGI), a DOE Office of Science User Facility, report sequencing the genomes of ten novel Aspergillus species, more than doubling the number of Aspergillus species sequenced to date. The newly sequenced genomes were compared with the eight other sequenced Aspergillus species. With this first-ever genus-wide view, the international consortium found that Aspergillus has a greater genomic and functional diversity than previously understood, broadening the range of potential applications for the fungi considered one of the most important workhorses in biotechnology. "Several Aspergillus species have already established status as cell factories for enzymes and metabolites. However, little is known about the diversity in the species at the genomic level and this paper demonstrates how diverse the species of this genus are," said study lead author Dr. Ronald de Vries of the Westerdijk Fungal Biodiversity Institute in the Netherlands.

Trial Being Planned for Using Mixture of Substances to Treat Fatty Liver Disease and Possibly Type 2 Diabetes; Human Protein Atlas Data Plays Key Role in Underlying Research

Researchers in Sweden are planning the clinical trial of a new treatment for non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes which harnesses liver cells’ own ability to burn accumulated fats. In a study involving 86 people with varying degrees of fatty liver disease, researchers from the KTH Royal Institute of Technology’s Science for Life Laboratory (SciLifeLab) research center and Gothenburg University found that the liver has the ability to burn up accumulated fats. The researchers propose a mixture of substances that will set this process in motion. One of the most common chronic liver problems in the world, the accumulation of fat in the liver (hepatic steatosis) is the key characteristic of NAFLD. It is linked to obesity, insulin resistance, type 2 diabetes, and cardiovascular diseases. Up to 30 percent of subjects with NAFLD develop non-alcoholic steatohepatitis (NASH) in which hepatic inflammation and scarring can lead to cirrhosis and liver cancer. The researchers mapped the metabolic changes caused by accumulated fat in 86 patients’ liver cells, and combined this data with an analysis of a genome-scale model of liver tissue. Doing so enabled them to identify the precise metabolic changes individual patients’ liver cells undergo due to fat. The results were published online on February 3, 2017 in Molecular Systems Biology. The open-access article is titled “Personal Model‐Assisted Identification of NAD+ and Glutathione Metabolism As Intervention Target in NAFLD.” Lead author Dr. Adil Mardinoglu, a systems biologist at KTH and a SciLifeLab fellow, is one of the researchers who had earlier established a connection between NAFLD and low levels of the antioxidant, glutathione (GSH).

March 3rd

Progeria-on-a-Chip Model Offers Insights into Premature Aging and Vascular Disease

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic condition that causes premature and accelerated aging. Recently, researchers have been able to generate induced pluripotent stem cells from patients with HGPS to better understand the mechanisms of aging and look for new treatments. HGPS primarily affects vascular cells, which undergo biomechanical strains in blood vessels. However, the impact of these biomechanical strains on aging and vascular diseases has been challenging to study in the lab as most models fail to mimic the biomechanics that cells experience in the body. Using a new progeria-on-a-chip model, investigators from Brigham and Women's Hospital, led by João Ribas, Ph.D. candidate, and Ali Khademhosseini, Ph.D., of the Biomaterials Innovation Research Center, have developed a way to recapitulate blood vessel dynamics to better understand vascular disease and aging. The new organ-on-a-chip device consists of a top fluidic channel and underlying vacuum channel, which mimics, upon pressure, the mechanical stretching that cells experience within blood vessels. The team found that cells derived from HGPS donors, but not from healthy donors, showed an exacerbated response to biomechanical strain, with an increase in markers of inflammation, which are strongly associated with vascular disease and aging. "Vascular diseases and aging are intimately linked yet rarely studied in an integrated approach," the authors write. "Gaining a deeper understanding of the molecular pathways regulating inflammation during vascular aging might pave the way for new strategies to minimizing cardiovascular risk with age." The open-access article, titled “Biomechanical Strain Exacerbates Inflammation on a Progeria-on-a-Chip Model," was published on February 17, 2017 in the journal Small.

Ten Million Lives Saved Globally by Vaccination Since Hayflick’s 1962 Development of Normal Human Cell Strain for Safe Vaccine Production; Data Marshalled in Opposition to Anti-Vaccine Movement

Nearly 200 million cases of polio, measles, mumps, rubella, varicella, adenovirus, rabies, and hepatitis A (and approximately 450,000 deaths from these diseases) were prevented in the U.S. alone between 1963 and 2015 by vaccination, researchers estimate. The study was published online on February 28, 2017 in AIMS Public Health. In 1963, vaccination against these infections became widespread, thanks to the development of a human cell strain that allowed vaccines to be produced safely. Globally, the vaccines developed from this strain and its derivatives prevented an estimated 4.5 billion cases of disease and saved more than 10 million lives. Author S. Jay Olshansky, Ph.D., Professor of Epidemiology and Biostatistics at the University of Illinois at Chicago (UIC) School of Public Health, was approached by co-author Leonard Hayflick, Ph.D., of the University of California, San Francisco (UCSF), who wanted to know how many lives had been saved by his development of cell strain WI-38. Hayflick developed the normal human cell strain in 1962, and it has been used ever since to safely grow the viruses needed to produce vaccines against more than 10 diseases. Before then, many viral vaccines had been grown in monkey cells, but contamination with potentially dangerous monkey viruses forced an end to this form of production, leaving millions vulnerable to common diseases. "Given the acknowledged large, positive global health impact of vaccines in general, I was curious what contribution my discovery of WI-38 in 1962 had in saving lives and reducing morbidity, since a large number of viral vaccines in use today are made with my cell strain or its derivatives," Dr. Hayflick said. To determine the number of cases of disease and deaths prevented by vaccines developed using WI-38, Dr.