Author: Nancy Fliesler

New angles for blocking Shiga and ricin toxins, and new light on an iconic biological process

Shiga toxin producing E. coli
Shiga-toxin-producing E. coli (IMAGE: JANICE HANEY CARR / USCDC)

Min Dong, PhD, and his lab are world experts in toxins and how to combat them. They’ve figured out how Clostridium difficile’s most potent toxin gets into cells and zeroed in on the first new botulinum toxin identified since 1969. Now, they’ve set their sights on Shiga and ricin toxins, and not only identified new potential lines of defense, but also shed new light on a fundamental part of cell biology: glycosylation.

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Restoring ‘youthful’ hemoglobin in sickle cell disease: First patient is symptom-free

Manny Johnson of Boston, 21, previously required monthly blood transfusions to keep his severe sickle cell disease under control. After receiving a new gene therapy treatment, he’s been symptom-free for six months.

Researchers at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center reported Manny’s case Saturday at the American Society of Hematology meeting in San Diego. Manny is their first patient, and an ongoing clinical trial will treat additional patients between ages 3 and 40.

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Microglia in the brain: Which are good and which are bad?

Timothy Hammond studying brain microglia in the Stevens Lab at Boston Children's Hospital
If we see microglia in brain disease, are they part of the problem, or part of the solution? asks Timothy Hammond. (PHOTOS: MICHAEL GODERRE / BOSTON CHILDREN’S HOSPITAL)

Microglia are known to be important to brain function. The immune cells have been found to protect the brain from injury and infection and are critical during brain development, helping circuits wire properly. They also seem to play a role in disease — showing up, for example, around brain plaques in people with Alzheimer’s.

It turns out microglia aren’t monolithic. They come in different flavors, and unlike the brain’s neurons, they’re always changing. Tim Hammond, PhD, a neuroscientist in the Stevens lab at Boston Children’s Hospital, showed this in an ambitious study, perhaps the most comprehensive survey of microglia ever conducted. Published last week in Immunity, the findings open a new chapter in brain exploration.

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Proposed cancer treatment may boost lung cancer stem cells, study warns

Epigenetic enzymes and lung cancer: Treating adenocarcinoma with G9a histone methyltransferase inhibitors leads to an increase in tumor cells with stem-like properties. In contrast, inhibiting histone demethylase prevents tumor growth. (SAMUEL ROWBOTHAM/BOSTON CHILDREN’S HOSPITAL)

Epigenetic therapies — targeting enzymes that alter what genes are turned on or off in a cell — are of growing interest in oncology as a way to make cancers less aggressive or less malignant. But now, at least one epigenetic therapy that had looked promising for lung cancer appears to boost the cancer stem cells that are believed to drive tumors. A study published today in Nature Communications also identifies a strategy that reduces these stem cells, curbing lung cancer in mice.

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‘Druggable’ cancer target found in pathway regulating organ size

Inactivating NUAK2 curbs cell proliferation in liver cancer
Reducing cancer proliferation: A small molecule that inactivates NUAK2, part of the Hippo/YAP pathway, reduces the number of cancerous cells in the mouse liver. (WEI-CHIEN YUAN/BOSTON CHILDREN’S HOSPITAL)

It’s known that cancer involves unchecked cell growth and that a pathway that regulates the size of organs, known as Hippo, is also involved in cancer. It’s further known that a major player in this pathway, YAP, drives many types of tumors. What’s been lacking is how to turn this knowledge into a practical cancer treatment. In a study published today in Nature Communications, researchers at Boston Children’s Hospital identify a target downstream of YAP, called NUAK2, and show that it can readily be inactivated with a small molecule.

“The Hippo pathway, and especially YAP, has been hard to target with drugs,” says senior study author Fernando Camargo, PhD, of Boston Children’s Stem Cell Research program. “This is the first demonstration of a ‘druggable’ molecule that could be targeted in any type of tumor driven by YAP.”

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Low-carb diets make us burn more calories, finds largest, longest feeding trial to date

Low carb diet helps us burn calories faster, supporting the Carbohydrate-Insulin Model of obesity
Supporting the Carbohydrate-Insulin Model of obesity, a new study finds that low-carb diets increase our energy expenditure.

Most people who diet to lose weight regain the pounds within a year or two, in part because the body adapts by slowing down metabolism and burning fewer calories. A new study known as the Framingham State Food Study, or (FS)2, suggests that low-carb diets can help people keep the weight off, showing that eating fewer carbohydrates increases the number of calories burned. The findings, published today in the BMJ, could help make obesity treatment more effective.

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Fishing for new leads in rare mucosal melanoma

Leonard Zon and Julien Ablain in the zebrafish facility
Leonard Zon and Julien Ablain are finding that zebrafish can tell us a lot about cancer. (PHOTO: SHANE HURLEY/BOSTON CHILDREN’S HOSPITAL)

Zebrafish are an emerging power tool in cancer research. They can be engineered to light up when certain genes turn on — capturing the moment when a cancer is initiated. Because they breed so quickly, they lend themselves to rapid, large-scale chemical screening studies, so can help identify tumor promoters and suppressors. Now, as a new study in Science demonstrates, zebrafish can also help scientists dissect the intricate molecular pathways that underlie many cancers, and could help guide treatment strategies — in this case, for mucosal melanoma.

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Could a simple injection fix spina bifida before birth?

Mesenchymal stem cells derived from amniotic fluid (FAUZA LAB / BOSTON CHILDREN’S HOSPITAL)

Ed. note: This is an update of a post that originally appeared in 2014.

The neural tube is supposed to close during the first month of prenatal development, forming the spinal cord and the brain. In children with spina bifida, it doesn’t close completely, leaving the nerves of the spinal cord exposed and subject to damage. The most common and serious form of spina bifida, myelomeningocele, sets a child up for lifelong disability, causing complications such as hydrocephalus, leg paralysis, and loss of bladder and bowel control.

A growing body of research from Boston Children’s Hospital, though still in animal models, suggests that spina bifida could be repaired at least partially early in pregnancy, through intrauterine injections of a baby’s own cells.

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Synapse ‘protection’ signal found; helps to refine brain circuits

a combination of 'eat me' and 'don't eat me' signals fine-tune synapse pruning
New evidence suggests that a ‘yin/yang’ system fine-tunes brain connections and synapse pruning (IMAGE: NANCY FLIESLER/ADOBE STOCK)

The developing brain is constantly forming new connections, or synapses, between nerve cells. Many connections are eventually lost, while others are strengthened. In 2012, Beth Stevens, PhD and her lab at Boston Children’s Hospital showed that microglia, immune cells that live in the brain, prune back unwanted synapses by engulfing or “eating” them. They also identified a set of “eat me” signals required to promote this process: complement proteins, best known for helping the immune system combat infection.

In new work published today in Neuron, Stevens and colleagues reveal the flip side: a “don’t eat me” signal that prevents microglia from pruning useful connections away.

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A Manhattan Project for the brain, at age 50

Formation of the IDDRCs in the 1960s launched a Manhattan project for the brain.
Landmark federal legislation in JFK’s final days launched an explosion of neuroscience research. (PHOTO ILLUSTRATION: NANCY FLIESLER/ADOBE STOCK)

On October 30th, 2018, Boston Children’s will be marking the 50th anniversary of the founding of its Intellectual and Developmental Disabilities Research Center.

As the African-American civil rights movement was flowering in the 1960s, a less visible civil rights movement was dawning. And so was a revolution in science that may outshine that spurred by the U.S. space program.

It was a time when children with what is now called intellectual disability (ID) or developmental disability (DD) were “excused” from school and routinely abandoned to institutions. “Schools” like the Fernald Center in Massachusetts and the Willowbrook State School in New York housed thousands of residents.

Some participated in research, but not the kind you might think. At Willowbrook, children were deliberately infected with hepatitis to test a new treatment. At Fernald, they were deliberately exposed to radiation in an experiment approved by the Atomic Energy Commission. Institutional review boards did not then exist.

In 1962, President John F. Kennedy convened a panel to propose a “National Action to Combat Mental Retardation,” at the strong urging of his sister Eunice Kennedy Shriver. Three weeks before JFK’s assassination, the first legislation passed. It changed the course of history.

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