Medulloblastoma is one of the most common pediatric brain tumors, accounting for nearly 10 percent of cases. It occurs in the cerebellum, a complex part of the brain that controls balance, coordination and motor function and regulates verbal expression and emotional modulation. While overall survival rates are high, current therapies can be toxic and cause secondary cancers. Developing alternative therapeutics is a priority for the field.
The World Health Organization updated the brain tumor classification scheme in 2016 to include these molecular and genetic features. In the new scheme, tumor subtypes with a good molecular prognosis receive less radiation and chemotherapy. But the creation of targeted therapeutics has remained a challenge, since some of the genetic pathways implicated in these subtypes are found in non-cancerous cells. …
The hepatitis B vaccine is one of only three vaccines that are routinely given to newborns in the first days of life. But the current hepatitis B vaccine has limitations: multiple “booster” doses are needed, and it can’t be given to premature babies weighing less than 2 kg.
Annette Scheid, MD, a neonatologist at Brigham and Women’s Hospital, is interested in leveraging infant immune differences to create a better hepatitis B vaccine for newborns. “The reality is that we have to vaccinate several times,” she says. “But we all dream of a vaccine that you give only once.” …
A quick look at recent research Vector finds noteworthy.
Tracking infants’ microbiomes
Microbiome studies are blooming as rapidly as bacteria in an immunocompromised host. But few studies have been done in children, whose microbiomes are actively forming and vulnerable to outside influences. Two studies in Science Translational Medicine on June 15 tracked infants’ gut microbiomes prospectively over time. The first, led by researchers at the Broad Institute and Massachusetts General Hospital, analyzed DNA from monthly stool samples from 39 Finnish infants, starting at 2 months of age. Over the next three years, 20 of the children received at least one course of antibiotics. Those who were repeatedly dosed had fewer “good” bacteria, including microbes important in training the immune system. Overall, their microbiomes were less diverse and less stable, and their gut microbes had more antibiotic resistance genes, some of which lingered even after antibiotic treatment. Delivery mode (cesarean vs. vaginal) also affected microbial diversity. A second study at NYU Langone Medical Center tracked 43 U.S. infants for two years and similarly found disturbances in microbiome development associated with antibiotic treatment, delivery by cesarean section and formula feeding versus breastfeeding. …
When we were developing in the womb, we were immersed in amniotic fluid. As our nervous systems formed, some of this fluid was trapped inside the neural tube, forming the cerebrospinal fluid that bathes our brains.
In the past, these fluids have been seen as a “cushion” or a place to dump waste products. But new research suggests that they actively participate in nervous system development.
Publishing this week in Developmental Cell, researchers led by Maria Lehtinen, PhD, and Kevin Chau in the Department of Pathology at Boston Children’s Hospital show that amniotic fluid and cerebrospinal fluid (CSF) contain rich portfolios of proteins that tell neural stem cells what to do — how to divide and what kinds of cells to make. They also show that the messages change in different phases of development. …
Nerve regeneration. From Santiago Ramón y Cajal’s “Estudios sobre la degeneración y regeneración del sistema nervioso” (1913-14). Via Scholarpedia.
First in a two-part series on nerve regeneration. Read part 2.
Researchers have tried for a century to get injured nerves in the brain and spinal cord to regenerate. Various combinations of growth-promoting and growth-inhibiting molecules have been found helpful, but results have often been hard to replicate. There have been some notable glimmers of hope in recent years, but the goal of regenerating a nerve fiber enough to wire up properly in the brain and actually function again has been largely elusive.
“The majority of axons still cannot regenerate,” says Zhigang He, PhD, a member of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. “This suggests we need to find additional molecules, additional mechanisms.”
Microarray analyses—which show what genes are transcribed (turned on) in injured nerves—have helped to some extent, but the plentiful leads they turn up are hard to analyze and often don’t pan out. The problem, says Judith Steen, PhD, who runs a proteomics lab at the Kirby Center, is that even when the genes are transcribed, the cell may not actually build the proteins they encode.
That’s where proteomics comes in. “By measuring proteins, you get a more direct, downstream readout of the system,” Steen says. …
Vast chunks of our DNA—fully 98 percent of our genome—are considered “non-coding,” meaning that they’re not thought to carry instructions to make proteins. Yet we already know that this “junk DNA” isn’t completely filler. For example, some sequences are known to code for bits of RNA that act as switches, turning genes on and off.
In a report published last month in Nature Communications, they describe a variety of proteins and peptides (smaller chains of amino acids) arising from presumed non-coding DNA sequences. Since they looked in just one type of cell—neurons—these molecules may only be the tip of a large, unexplored iceberg and could change our understanding of biology and disease. …
A good biomarker is one whose levels go up or down as a patient’s disease worsens or wanes. A great biomarker also gives key insights into disease development. A really great biomarker does both of these things and also serves as a treatment target.
Part 1 of a two-part series on kidney disease. Part 2 is here.
In up to 5 percent of all pregnancies, children are born with some degree of kidney dilation or swelling, known as hydronephrosis. Unfortunately, says urologist Richard Lee, MD, of Boston Children’s Hospital, “many of these kids go through a lot of testing after birth and are followed for a long period of time—sometimes unnecessarily.”
Hoping to reduce such testing, Lee and his colleagues are turning to urine. They’ve been collecting comprehensive data on the urinary proteome—all the proteins urine normally contains. With this baseline information, they hope to establish biomarkers that identify kidney damage.
In a recently published study, Lee and his coauthors compared the urinary proteomes of healthy infant boys versus men to find out what happens naturally with age. Through their work, they identified nearly 1,600 protein groups and determined that the healthy male urinary proteome changes over time. …
Your doctor has a lot of tools to detect, diagnose and monitor disease: x-rays, MRIs, angiography, blood tests, biopsies…the list goes on.
What would be great would be the ability to test for disease in a way where there’s no or low pain (not invasive) and lots of gain (actionable data about the disease process itself, its progression and the success of treatment).
“What is proteomics?” Answering this simple question was the motivation for the Proteomics 2011, an annual symposium hosted by Judith and Hanno Steen of the Steen & Steen lab and The Proteomics Center at Children’s, featuring global innovators and local advances in proteomics at Children’s Hospital Boston, held last week. As a video at the start of the symposium showed, it’s a question that elicits a wide range of answers: