Protecting damaged hearts with microRNAs

microRNAs facilitate cardiac regeneration after a heart attack
New work advances the possibility of regenerating cardiac tissue after a heart attack. (PHOTO: ADOBE STOCK)

Once the heart is fully formed, the cells that make up heart muscle, known as cardiomyocytes, have very limited ability to reproduce themselves. After a heart attack, cardiomyocytes die off; unable to make new ones, the heart instead forms scar tissue. Over time, this can set people up for heart failure.

New work published last week in Nature Communications advances the possibility of reviving the heart’s regenerative capacities using microRNAs — small molecules that regulate gene function and are abundant in developing hearts.

In 2013, Da-Zhi Wang, PhD, a cardiology researcher at Boston Children’s Hospital and a professor of pediatrics of Harvard Medical School, identified a family of microRNAs called miR-17-92 that regulates proliferation of cardiomyocytes. In new work, his team shows two family members, miR-19a and miR-19b, to be particularly potent and potentially good candidates for treating heart attack.

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Probing the mystery of drug resistance: New hope for leukemia’s toughest cases

Alejandro Gutierrez, MD, was inspired by the deaths of three patients to figure out how leukemia cells become resistant to drugs.
Alejandro Gutierrez, MD
(PHOTO: MICHAEL GODERRE / BOSTON CHILDREN’S HOSPITAL)

Three children Alejandro Gutierrez, MD, treated for leukemia during his fellowship at Boston Children’s Hospital still haunt him more than a decade later. One 15-year-old boy died from the toxicity of the drugs he was given; the other two patients went through the whole treatment only to die when their leukemia came back. “That really prompted a deep frustration with the status quo,” Gutierrez recalls. “It’s motivated everything I’ve done in the lab since then.”

Gutierrez, now a researcher in the Division of Hematology/Oncology, has made it his mission to figure out why leukemia treatments cure some patients but not others. And in today’s issue of Cancer Cell, he and 15 colleagues report progress on two important fronts: They shed light on how leukemia cells become resistant to drugs, and they describe how two drugs used in combination may overcome that resistance, offering new hope to thousands of children and adults with leukemia.

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EEG patterns diverge in babies of stressed mothers

Study of newborn EEG and maternal stress
A study in JAMA Pediatrics assessed new mothers’ stress levels and EEG patterns in their 2-month-old babies. Such patterns could help flag infants at risk.(PHOTO: EMILY REILLY / BOSTON CHILDREN’S HOSPITAL)

Does exposure to stress early in life affect a baby’s brain development, and is there a way to single out babies who might benefit from early intervention? A two-center study led by Boston Children’s Hospital, published today in JAMA Pediatrics, used brain EEGs to begin to get at these questions in an objectively measurable way. It found that infants whose mothers reported high levels of stress have a distinct pattern of brain activity as measured by EEG — at only 2 months of age.

“The EEG has been found to be exquisitely sensitive to perturbations in the environment, and thus we are not entirely surprised to see an association between stress in a mother’s life and her infant’s brain activity,” says Charles Nelson, PhD, director of the Laboratories of Cognitive Neuroscience at Boston Children’s Hospital and the study’s senior investigator. “What we were surprised by, in part, was how early in life we see this association.”

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‘Nanobodies’ from alpacas could help bring CAR T-cell therapy to solid tumors

These alpacas produce the unusually small antibodies (nanobodies) used in a new form of CAR T-cell therapy
Like other alpacas, as well as camels and llamas, Bryson (left) and Sanchez produce unusually small antibodies that could have a role in cancer immunotherapy. (PHOTO COURTESY HIDDE PLOEGH / BOSTON CHILDREN’S HOSPITAL)

In 1989, two undergraduate students at the Free University of Brussels were asked to test frozen blood serum from camels, and stumbled on a previously unknown kind of antibody. It was a miniaturized version of a human antibody, made up only of two heavy protein chains, rather than two light and two heavy chains. As they eventually reported, the antibodies’ presence was confirmed not only in camels, but also in llamas and alpacas.

Fast forward 30 years. In the journal PNAS this week, researchers at Boston Children’s Hospital and MIT show that these mini-antibodies, shrunk further to create so-called nanobodies, may help solve a problem in the cancer field: making CAR T-cell therapies work in solid tumors.

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More efficient gene editing for blood stem cells could ease hemoglobin disorders

A new CRISPR strategy overcomes prior technical challenges. IMAGE: NANCY FLIESLER / ADOBE STOCK

The ability to edit genes in patients’ blood stem cells — which produce red blood cells, platelets, immune cells and more — offers the potential to cure many genetic blood disorders. If all goes well, the corrected cells engraft in the bone marrow and produce healthy, properly functioning blood cells… forever.

But scientists have had difficulty introducing edits into blood stem cells. The efficiency and specificity of the edits and their stability once the cells engraft in the bone marrow have been variable.

A new approach, described this week in Nature Medicine and in January in the journal Blood, overcomes prior technical challenges, improving the efficiency, targeting and durability of the edits. Researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and the University of Massachusetts Medical School successfully applied the technique to two common blood diseases — sickle cell disease and beta thalassemia — involving mutations in the gene for beta globin protein.

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Mobilizing the immune system’s ‘natural killers’ against inflammatory bowel disease

Stripped of their STAT1 protein “shield,” the helper T cells that cause inflammatory
bowel disease are wiped out by the immune system’s “natural killer” (NK) cells.
(ILLUSTRATION: FAWN GRACEY)

The human immune system includes about a dozen major cell types with specialized roles in the body’s defenses. They serve as sentries, identify threats, mobilize troops, capture and transport invaders, interrogate and kill those deemed dangerous and clear the battlefield of casualties. This intricate command-and-control system is what enables us to fend off most of the dangerous bacteria and viruses that come our way.

But in patients who suffer from inflammatory bowel disease (IBD), the immune system itself becomes the enemy. Even when the body faces no threat, immune cells called “helper T cells” take up arms, resulting in a kind of perpetual warfare that — far from being helpful — causes collateral damage to the gut.

“The system goes into overdrive,” says Yu Hui Kang, an immunology graduate student at Harvard Medical School and a researcher at Boston Children’s Hospital. “These cells have gone too far, and they can’t stop.”

Now Kang and colleagues in the lab of Scott Snapper, MD, PhD, director of Boston Children’s Inflammatory Bowel Disease Center, may have found a way to turn the tables on the immune system by recruiting its own “natural killer” cells to wipe out the harmful T cells. Though clinical applications are years away, the work suggests new avenues for developing treatments for the debilitating disease.

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Dually-targeted liposomes curb triple-negative breast cancer, metastases in mice

dual targeting for triple-negative breast cancer
(IMAGE: ADOBE STOCK)

Some 15 to 20 percent of all breast cancers are triple-negative, meaning they lack receptors for estrogen, progesterone and human epidermal growth factor type 2. They have the worst prognosis of all breast cancers and very limited treatment options. Finding a treatment that distinguishes between cancer cells and normal cells has been especially challenging.

A novel precision medicine strategy described today in Science Advances offers an intriguing ray of hope. Researchers at Boston Children’s Hospital, with bioengineers at the City College of New York (CCNY), showed that dually-targeted, antibody-guided nanoparticles, loaded with an existing chemotherapy drug, markedly improved tumor targeting, decreased tumor and metastatic growth and dramatically improved survival in a mouse model of triple-negative breast cancer. There were no observable side effects.

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Biological explorers find new player in the formation of the nervous system

Tom Schwarz recently found a new function for the kinetochore
(PHOTO: MICHAEL GODERRE / BOSTON CHILDREN’S HOSPITAL)

Tom Schwarz, PhD, is a cell biologist who conducts his research in a cluttered laboratory overlooking Boston Children’s Hospital. But he likens his scientific approach to that of the great explorers of the past.  “It’s like marching off into the jungle,” he says, “because you really don’t know what you’re going to find.”

Schwarz and colleagues at the F.M. Kirby Neurobiology Center have just returned from an “expedition” that could profoundly change our understanding of how the nervous system forms — and give an unexpected new role to an old standby in cell biology: the kinetochore.

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Small samples, big data: A systems-biology look at a newborn’s first week of life

newborn biology, through tiny blood samples
(PHOTO: ADOBE STOCK)

The first week of a baby’s life is a time of rapid biological change. The newborn must adapt to living outside the womb, suddenly exposed to new bacteria and viruses. Yet scientists know surprisingly little about these early changes.

Reporting in today’s Nature Communications, an international research team provides the most detailed accounting to date of the molecular changes that occur during a newborn’s first seven days. The team pioneered a technique to extract volumes of data from a tiny amount of newborn blood — including what genes are turned on, what proteins the body is making and what metabolites are changing.

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The threat from mosquito-borne diseases: Forecasting mosquitoes’ global spread

Aedes albopictus
Aedes albopictus (ADOBE STOCK)

Outbreaks of mosquito-borne illnesses like yellow fever, dengue, Zika and chikungunya are rising around the world. Climate change has created conditions favorable to mosquitoes’ spread, but so have human travel and migration and accelerating urbanization, creating new mini-habitats for mosquitoes.

In Nature Microbiology yesterday, a large group of international collaborators combined these factors into prediction models that offer insight into the recent spread of two key disease-spreading mosquitoes — Aedes aegypti and Aedes albopictus. The models forecast that by 2050, 49 percent of the world’s population will live in places where these species are established if greenhouse gas emissions continue at current rates.

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