New research helps explain why men are three to five times more likely to develop bladder cancer than women.
Using mouse models and human patient data, Boston Children’s Hospital researchers in the urology department, Xue Sean Li, PhD, and Satoshi Kaneko, PhD, found that inherent genomic differences contribute to the contrast in bladder cancer rate between males and females. …
When the 1-year-old boy arrived from overseas, he was relying on total parenteral nutrition — a way of bypassing the digestive system to provide nutrients and calories completely intravenously — to survive. From the time of his birth, he had experienced unexplainable diarrhea. Answers were desperately needed.
Sequencing his genes in search of clues, neonatologists and collaborators at the Manton Center for Orphan Disease Research at Boston Children’s Hospital identified a new gene mutation responsible for chronic congenital diarrhea — even finding a similar mutation in two other children as well.
Using patient-derived intestinal organoids in the laboratory, the team discovered that the newly-identified gene mutation, WNT2B, appears to stifle intestinal stem cells’ normal function and growth. The findings were published in the American Journal of Human Genetics.
Malaria parasite infection, which affects our red blood cells, can be fatal. Currently, there are about 200 million malaria infections in the world each year and more than 400,000 people, mostly children, die of malaria each year.
Now, studying blood samples from patients treated for malaria at a clinical field station in Brazil’s Amazon jungle, a team of Brazilian and American researchers has made a surprising discovery that could open the door to a new vaccine.
“I noticed that white blood cells called killer T cells were activated in response to malaria parasite infection of immature red blood cells,” says Caroline Junqueira, PhD, a visiting scientist at Boston Children’s Hospital and Harvard Medical School (HMS).
Digging deeper, Junqueira, Lieberman and collaborators have found a completely unexpected immune response to malaria parasites that infect immature blood cells called reticulocytes. The revelation could help to design a new vaccine that might be capable of preventing malaria.
Their findings, published today in Nature Medicine, uncover special cellular mechanisms and properties specific to “teenaged” reticulocytes and a strain of malaria called Plasmodium vivax that enable our T cells to recognize and destroy both the infected reticulocytes and the parasites inside them. …
Animal cloning, the creation of a genetically identical copy of an individual organism, holds promise for many different reasons, including its use to conserve endangered species and to improve our understanding of developmental biology, which could eventually help us prevent or reverse developmental disorders from the get-go. Although more than 20 species of animals have been cloned so far, cloning efficiency, or the percent of successful live births, has remained universally low and economically out of reach for most practical applications.
But now, researchers at Boston Children’s Hospital have reported a new cloning technique that has yielded the highest efficiency ever reported in mouse cloning, capable of producing 13 to 16 times more mouse pups than previous methods. The findings were reported in Cell Stem Cell.
A new discovery about the spatial orientation and physical interactions of our genes provides a promising step forward in our ability to design custom antibodies. This, in turn, could revolutionize the fields of vaccine development and infection control.
Recent years of research by Alt and others in the field of molecular biology have revealed that it’s not just our genes themselves that determine health and disease states. It’s also the three-dimensional arrangement of our genes that plays a role in keeping genetic harmony. Failure of these structures may trigger genetic mutations or genome rearrangements leading to catastrophe.
The importance of genetic loops
Crammed inside the nucleus, chromatin, the chains of DNA and proteins that make up our chromosomes, is arranged in extensive loop arrangements. These loop configurations physically confine segments of genes that ought to work together in a close proximity to one another, increasingly their ability to work in tandem.
“All the genes contained inside one loop have a greater than random chance of coming together,” says Suvi Jain, PhD, a postdoctoral researcher in Alt’s lab and a co-first author on the study.
Meanwhile, genes that ought to stay apart remain blocked from reaching each other, held physically apart inside our chromosomes by the loop structures of our chromatin.
But while many chromatin loops are hardwired into certain formations throughout all our cells, it turns out that some types of cells, such as certain immune cells, are more prone to re-arrangement of these loops. …
For decades, cardiac researcher James McCully, PhD, has been spellbound by the idea of using mitochondria, the “batteries” of the body’s cells, as a therapy to boost heart function. Finally, a clinical trial at Boston Children’s Hospital is bringing his vision — a therapy called mitochondrial transplantation — to life.
Mitochondria, small structures inside all of our cells, synthesize the essential energy that our cells need to function. In the field of cardiac surgery, a well-known condition called ischemia often damages mitochondria and its mitochondrial DNA inside the heart’s muscle cells, causing the heart to weaken and pump blood less efficiently. Ischemia, a condition of reduced or restricted blood flow, can be caused by congenital heart defects, coronary artery disease and cardiac arrest.
For the smallest and most vulnerable patients who are born with severe heart defects, a heart-lung bypass machine called extracorporeal membrane oxygenation (ECMO) can help restore blood flow and oxygenation to the heart. But even after blood flow has returned, the mitochondria and their DNA remain damaged.
“In the very young and the very old, especially, their hearts are not able to bounce back,” says McCully.
Ischemia can be fatal for the tiniest patients
After cardiac arrest, for instance, a child’s mortality rate jumps to above 40 percent because of ischemia’s effects on mitochondria. If a child’s heart is too weak to function without the support of ECMO, his or her risk of dying increases each additional day spent connected to the machine.
But what if healthy mitochondria could come to the rescue and replace the damaged ones? …
The hope to improve people’s lives is what drives many members of industry and academia to bring new products and therapies to market. At the BIO International Convention last week in Boston, there was lots of discussion about how translational science intersects with patients’ needs and why the best therapeutic developmental pipelines are consistently putting patients first.
“Our mission is to de-risk entry of new therapies in the ASD drug discovery and development space,” said Sahin, who is also a professor of neurology at Harvard Medical School.
One big challenge, says Sahin, is knowing how well — or how poorly — autism therapies are actually affecting people with ASD. Externally, ASD is recognized by its core symptoms of repetitive behaviors and social deficits. …
This is part I of a two-part blog series recapping the 2018 BIO International Convention.
At the 2018 BIO International Convention last week, it was clear what’s provoking scientific minds in industry and academia — or at least those of the Guinness-world-record-making 16,000 people in attendance. Artificial intelligence, machine learning and their implications for tailor-made medicine bubbled up across all BIO’s educational tracks and a majority of discussions about the future state of biotechnology. Panelists from Boston Children’s Hospital also contributed their insights to what’s brewing at the intersection of these burgeoning fields.
Isaac Kohane, MD, PhD, former chair of Boston Children’s Computational Health and Informatics Program, spoke on a panel about how large-scale patient data — if properly harnessed and analyzed for health and disease trends — is a virtual goldmine for precision medicine insights. Patterns gleaned from population health data or electronic health records, for example, could help identify which subgroups of patients who might respond better to specific therapies.
According to Kohane, who is currently the Marion J. Nelson Professor of Biomedical Informatics and Pediatrics at Harvard Medical School (HMS), we will soon be leveraging artificial intelligence to go through patient records and determine exactly what doctors were thinking when they saw patients.
“We’ve seen again and again that data abstraction by artificial intelligence is better than abstraction by human analysts when performed at the scale of millions of clinical notes across thousands of patients,” said Kohane.
And based on what we heard at BIO, artificial intelligence will revolutionize more than patient data mining. It will also transform the way we design precision therapeutics — and even vaccines — from the ground up. …
For more than 15 years, pediatric neuro-oncologist Mariella Filbin, MD, PhD, has been on a scientific crusade to understand DIPG (diffuse intrinsic pontine glioma). She hopes to one day be able to cure a disease that has historically been thought of as an incurable type of childhood brain cancer.
“While I was in medical school, I met a young girl who was diagnosed with DIPG,” Filbin recalls. “When I heard that there was no treatment available, I couldn’t believe that was the case. It really made a huge impression on me and since then, I’ve dedicated all my research to fighting DIPG.”
Her mission brought her to Boston Children’s Hospital for her medical residency program and later, to do postdoctoral research at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Now, she’s starting her own research laboratory focused on DIPG — which has also been called diffuse midline glioma (DMG) in recent years — and continuing to treat children with brain tumors at the Dana-Farber/Boston Children’s pediatric brain tumor treatment center. She’s also a scientist affiliated with the Broad Institute Cancer Program.
This year, Filbin has made new impact in the field by leveraging the newest single-cell genetic sequencing technologies to analyze exactly how DIPG develops in the first place. Her latest research, published in Science, entailed profiling more than 3,300 individual brain cells from biopsies of six different patients.
Using what’s known as a single-cell RNA sequencing approach to interrogate the makeup of DIPG/DMG tumors, Filbin was able to identify a particularly problematic type of brain cell that acts forever young, constantly dividing over and over again in a manner similar to stem cells. …
Over-prescribing has long been thought to increase antibiotic resistance in bacteria. But could much bigger environmental pressures be at play?
While studying the role of climate on the distribution of antibiotic resistance across the geography of the U.S., a multidisciplinary team of epidemiologists from Boston Children’s Hospital found that higher local temperatures and population densities correlate with higher antibiotic resistance in common bacterial strains. Their findings were published today in Nature Climate Change.
“The effects of climate are increasingly being recognized in a variety of infectious diseases, but so far as we know this is the first time it has been implicated in the distribution of antibiotic resistance over geographies,” says the study’s lead author, Derek MacFadden, MD, an infectious disease specialist and research fellow at Boston Children’s Hospital. “We also found a signal that the associations between antibiotic resistance and temperature could be increasing over time.”
During their study, the team assembled a large database of U.S. antibiotic resistance in E. coli, K. pneumoniae and S. aureus, pulling from hospital, laboratory and disease surveillance data documented between 2013 and 2015. Altogether, their database comprised more than 1.6 million bacterial specimens from 602 unique records across 223 facilities and 41 states. …