Posts by author:

Nancy Fliesler

Using a novel 3-D culture method, scientists were able to prod lung (bronchioalveolar) stem cells to produce colonies containing the cell type of choice: airway (bronchiolar) epithelial cells, alveolar epithelial cells or both. (Images: Joo-Hyeon Lee)

Using a novel 3-D culture method, scientists were able to prod lung (bronchioalveolar) stem cells to produce colonies with the cell type of choice: airway (bronchiolar) epithelial cells, alveolar epithelial cells or both. (Images: Joo-Hyeon Lee)

Someday it may be possible to treat lung diseases like emphysema, pulmonary fibrosis or asthma by prodding the lungs to produce healthy versions of the cells that are damaged.

That’s the hope of researchers Carla Kim, PhD, and Joo-Hyeon Lee, PhD, of the Stem Cell Research Program at Boston Children’s Hospital. In the Jan. 30 issue of Cell, they describe a pathway in the lungs, activated by injury, that directs stem cells to transform into specific kinds of cells—and that can be manipulated to enhance different kinds of repair, at least in a mouse model.

By boosting the pathway, Kim, Lee and colleagues successfully increased production of alveolar epithelial cells, which line the lung’s alveoli—the tiny sacs where gas exchange takes place, and that are irreversibly damaged in diseases like pulmonary fibrosis and emphysema. Full story »

Leave a comment

The footpads of diabetic mice (line-D) treated with a cream containing XIB4035 have increased numbers of nerve terminals (shown in green in the lower right panel), whereas mice given a control cream (lower left) do not. The top two panels represent healthy “wild type” mice.

The footpads of diabetic mice given a cream containing XIB4035 (lower right) have new nerve terminals (shown in green), whereas mice given a control cream (lower left) do not. The top two panels represent healthy “wild type” mice.

About half of people with diabetes develop peripheral neuropathy. The most common form, small-fiber neuropathy, generally starts in the feet, causing pain, odd sensations like pricks and “pins and needles,” and—the most worrisome feature—a loss of sensation that can increase the chance of ulcers and infections.

In some cases, that may lead to the need for amputation—as happened with my diabetic great-grandfather whose numbed feet, unbeknownst to him, got too close to the fire.

While there are some treatments to reduce pain, there’s nothing that restores sensation. Nor do any existing treatments address the underlying cause of the neuropathy: the degeneration or dysfunction of the endings of the sensory neurons in the skin. Full story »

5 comments

asthmatic airway

Obesity may set off innate immune factors that inflame the lungs.

Both asthma and obesity have surged in recent decades, and a growing body of literature is linking the two conditions. Various explanations have been proposed: One recent study suggests that hormonal factors in obesity may regulate airway diameter; another suggests that obesity activates asthma-related genes.

“Why obesity predisposes a person to asthma has been a real puzzle,” says Dale Umetsu, MD, PhD, who recently researched the problem with Hye Young Kim, PhD, and other colleagues in the Division of Allergy and Immunology at Boston Children’s Hospital. “Our goal was to find the connection between these two problems, which occur in both children and adults, and to explore possible new treatments.”

The team’s research indicates that obesity alters the innate immune system—the body’s first responder to infection—in several ways, resulting in lung inflammation. Published earlier this month in Nature Medicine, their work also suggests a completely new, “druggable” approach to treating patients with obesity-associated asthma, for whom standard asthma drugs often work poorly. Full story »

Leave a comment

Normal brain and Double Cortex-Courtesy Christopher Walsh(Above: In double cortex syndrome, causing epilepsy and mental retardation, an extra cortex forms just beneath the cerebral cortex [right]. The causative DCX mutation interferes with migration of neurons during the cortex’s early development. Courtesy Walsh Lab)

The journal Neuron, celebrating its 25th anniversary, recently picked one influential neuroscience paper from each year of the publication. In this two-part series, we feature the two Boston Children’s Hospital’s scientists who made the cut. The Q&A below is adapted with kind permission from Cell Press. (See part 1)

Key to well-tuned brain function is the migration of neurons to precise locations as the brain develops. The long journey begins deep inside the brain and ends in the outer cerebral cortex—where our highest cognitive functions lie. Christopher Walsh, MD, PhD, has shown that several genetic mutations causing neurodevelopmental disorders disrupt this neuronal migration, landing neurons in the wrong places. Each gene governs a specific sub-task: one kicks off the migration process; others stop migration when neurons have arrived in the right location. Full story »

Leave a comment

Microglial cell in visual system

Caught in the act: This microglial cell receives visual input from the eyes. The blue and red dots (inputs from the same-side and opposite-side eye, respectively) are synapses the cell has engulfed—the first step in eliminating synapses the brain no longer needs.

The journal Neuron, celebrating its 25th anniversary, recently picked one influential neuroscience paper from each year of the publication. In this two-part series, we feature the two Boston Children’s Hospital’s scientists who made the cut. The Q&A below is adapted with kind permission from Cell Press.

In 2012, Beth Stevens, PhD, and colleagues provided a new understanding of how glial cells shape healthy brain development. Glia were once thought to be merely nerve “glue” (the meaning of “glia” from the Greek), serving only to protect and support neurons. “In the field of neuroscience, glia have often been ignored,” Stevens told Vector last year.

No longer. Stevens’s 2012 paper documented that microglia—glial cells best known for their immune function—are no passive bystanders. They get rid of excess connections, or synapses, in the developing brain the same way they’d dispatch an invading pathogen—by eating them. Full story »

Leave a comment

Single peanut unsalted-ShutterstockTripp Underwood contributed to this post.

Families with peanut-allergic children live in fear that their child will ingest peanuts—even minute amounts—accidentally. Now, a small pilot study published in the Journal of Allergy and Clinical Immunology offers hope.

In the year-long study, immunologist Dale Umetsu, MD, PhD, and colleagues in the Division of Allergy and Immunology at Boston Children’s Hospital were able to get some children to tolerate as many as 20 peanuts at a time. Their protocol combines a powerful anti-allergy medication with a methodical desensitization process.

While it’s not a cure, the protocol may enable children to weather trace amounts of peanuts that might lurk in baked goods or foods “manufactured in a facility that processes peanuts.” Even a small amount of peanut tolerance could be lifesaving. Full story »

Leave a comment

Cell cover about using zebrafish and iPS cells to find muscle-building drugs.

In a one-two-three punch, a rapid screen in zebrafish can quickly identify a short list of drug candidates to test in mice and in patient-derived cells.

Scientists have had little success in growing skeletal muscle for patients with muscular dystrophy and other disorders that degrade and weaken muscle. Undertaking experiments in zebrafish, mouse and human cells, researchers have identified a way to do that, creating cells that Leonard Zon, MD, hopes to see tested in patients in the next several years.

But what really excites Zon, director of the Stem Cell research program at Boston Children’s Hospital, is the power of the chemical screening platform he and his colleagues used. Described last week in the journal Cell, it found a cocktail of three compounds that induced human muscle cells to grow—in just a matter of weeks. Zon believes it could fast-track drug discovery for multiple disorders. Full story »

Leave a comment

New research reinforces the idea that an inborn vulnerability can tip infants toward SIDS.

New research reinforces that inborn vulnerabilities can tip infants toward SIDS.

Epidemiologic studies have shown that infants who die suddenly, unexpectedly and without explanation—what’s referred to as sudden infant death syndrome, or SIDS—are often found sleeping face down with their face in the pillow, or sleeping next to an adult. These are environments that have the potential to cause smothering and asphyxiation. By advising parents to have infants sleep on their backs, in a separate crib or bed, the government’s Safe to Sleep campaign (formerly known as Back to Sleep) has greatly reduced deaths from SIDS.

Hannah Kinney, MD, a neuropathologist at Boston Children’s Hospital, is clear that this campaign must go forward—it’s saved thousands of lives. But still, she receives calls from parents and grandparents haunted by their infants’ death, feeling at fault and wanting a second opinion.

And in many cases, she has been able to document abnormalities in brainstem circuits that help control breathing, heart rate, blood pressure and temperature control during sleep.

What’s lacking is early detection and treatment. Full story »

Leave a comment

Three clinics are pre-testing children for genetic variants likely to affect their response to drugs.

Three clinics are pre-testing children for genetic variants likely to affect their response to drugs.

In 2009, The New England Journal of Medicine reported the case of an otherwise healthy 2-year-old boy in Canada who died after surgery. He had received a codeine dose in the recommended range, but an autopsy revealed that morphine (a product of codeine metabolism) had built up to toxic levels in his blood and likely depressed his breathing. Genetic profiling revealed him to be an “ultrarapid codeine metabolizer,” due to a genetic variation in an enzyme known as CYP2D6, part of the cytochrome P-450 family.

While codeine is no longer used at Boston Children’s Hospital, it’s this kind of genetic profiling that Shannon Manzi, PharmD, would someday like to offer to all patients—before a drug is prescribed.

Not all people respond the same way to drugs. The results of randomized clinical trials—considered the gold standard for drug testing—often produce a dose range that worked for the majority of the patients in the study. They don’t take people’s individuality into account, and that individuality can dramatically affect drug efficacy and toxicity.

Adverse reactions are more common than you might think. Full story »

Leave a comment

In mice, VEGF-A modRNA visibly improved blood supply to heart muscle (right image).

In mice, VEGF-A modRNA visibly improved blood supply to heart muscle (right image) as compared with no treatment.

Heart attacks cause the death of billions of the heart’s muscle cells. If these cardiomyocytes could be made to regenerate after an infarct, the heart could potentially be mended and its function restored.

Researchers have struggled to find the right approach to regeneration. Cell transplants have been tried, but the cells don’t engraft well long term and haven’t shown efficacy. Gene therapy to spur regeneration has been tested in animals, but dosage is hard to control and there’s a risk of genes going where they shouldn’t, causing tumors and other problems. Protein drugs have been tried, but they have short half-lives, being degraded or eliminated by the body before they can do much good. They are also hard to target to the heart.

A more recent approach to cardiac regeneration is to stimulate the body itself—and, specifically, progenitor cells— to repair the heart from within. Full story »

Leave a comment