Author: Kat J. McAlpine

Another microbiome perspective: The host holds the leash

Abstract depiction of the microbiome

Most scientists and clinicians accept that the human microbiome impacts a person’s nutrition, immune system function, physical health and perhaps even mental illness, but exactly how or why is not well understood. Now, taking an evolutionary approach, a Boston Children’s Hospital infectious disease researcher suggests the host may play a more active role in controlling the microbiome than previously appreciated.

“I think we need to re-evaluate the way in which we think about the microbiome,” says Seth Rakoff-Nahoum, MD, PhD, a physician-scientist at Boston Children’s in the Divisions of Infectious Diseases and Gastroenterology, whose perspective was published today in Nature.

Read Full Story | Leave a Comment

Severe flu infections linked to underlying genetic variation

Flu virusesThe Center for Disease Control estimates that influenza virus–related illnesses account for more than 200,000 U.S. hospitalizations and 12,000 deaths annually. Young children, the elderly and people with respiratory, cardiac and other chronic health conditions are at particularly high risk for being hospitalized for influenza-related complications. Until now, there has not been a clear reason to explain why some individuals become severely ill from flu and not others.

New findings published in Nature Medicine, however, might change that.

“We’ve identified a genetic variant that we believe may put people at risk of getting life-threatening influenza infections,” says Adrienne Randolph, MD, MSc, a senior associate in pediatric critical care medicine at the Boston Children’s Hospital.

Read Full Story | Leave a Comment

CRISPR enables cancer immunotherapy drug discovery

Artwork depicting cancer cells with different genes deleted by CRISPR-Cas9, performed to identify novel cancer immunotherapy targets
These cancer cells (colored shapes) each have a different gene deleted through CRISPR-Cas9 technology. In a novel genetic screening approach, the T cells (red) destroy those cancer cells that have lost genes essential for evading immune attack, revealing potential drug targets for enhancing PD-1-checkpoint-based cancer immunotherapy. Credit: Haining Lab 

A novel screening method using CRISPR-Cas9 genome editing technology has revealed new drug targets that could potentially enhance the effectiveness of PD-1 checkpoint inhibitors, a promising new class of cancer immunotherapy.

The method, developed by a team at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, uses CRISPR-Cas9 to systematically delete thousands of tumor genes to test their function in a mouse model. In findings published today by Nature, researchers led by pediatric oncologist W. Nick Haining, BM, BCh report that deletion of one gene, Ptpn2, made tumor cells more susceptible to PD-1 checkpoint inhibitors. Other novel drug targets are likely around the corner.

PD-1 inhibition “releases the brakes” on immune cells, enabling them to locate and destroy cancer cells. But for many patients, it’s not effective enough on its own.

Read Full Story | Leave a Comment

SIDS associated with higher blood serotonin levels

A baby sleeping on its back, which is the safest sleeping position to prevent SIDS
The Safe to Sleep campaign has helped reduce SIDS deaths, but underlying causes for SIDS have largely remained mysterious.

Sudden infant death syndrome (SIDS) accounts for the greatest share of deaths in children between the ages of 1 and 12 months. What if a blood test could explain a third of SIDS deaths – and in the future, help prevent them? New findings by a Boston Children’s Hospital team show that an increased level of serotonin in blood serum may underpin some SIDS deaths and suggests the possibility that this biological vulnerability may one day be detected in the blood of living infants.

While there are known risk factors for SIDS — such as sleeping face-down or on soft surfaces — how and why such seemingly minor threats kill some children, and not others, remains a mystery.

“Research on the underlying pathology of SIDS is critical to further our understanding of the biological mechanisms contributing to a SIDS death,” says Robin Haynes, PhD, a researcher in the Department of Pathology at Boston Children’s Hospital.

Read Full Story | Leave a Comment

A new inlet to treating neurological disease

Image of brains showing red tracer dye, indicating passage of molecules through the blood-brain barrier
These brain images tell a story about the blood-brain barrier: At left, the brain before injection of red tracer dye. At center, an injection of tracer dye shows only a small amount of molecules can infiltrate the blood brain barrier. At right, a new approach for crossing the blood-brain barrier increases the tracer’s penetration into brain tissue.

The blood-brain barrier was designed by nature to protect the brain and central nervous system (CNS) from toxins and other would-be invaders in the body’s circulating blood. Made up of tightly-packed cells, the barrier allows nutrients to pass into the CNS and waste products from the brain to be flushed out, while blocking entry of harmful substances.

A dysfunctional blood-brain barrier can contribute to CNS diseases including Alzheimer’s and multiple sclerosis (MS). But, ironically, the same blood-brain barrier can keep out drugs intended to treat CNS disease. Scientists have long been seeking ways to overcome this obstacle.

Now, Timothy Hla, PhD, and members of his laboratory in the Boston Children’s Hospital Vascular Biology Program have found a way to selectively control openings in the blood brain barrier to allow passage of small drug molecules.

Read Full Story | Leave a Comment

A surprising new link between inflammation and mental illness — and a potential drug to protect the brain

A synapse being attacked by microglia, which causes neuropsychiatric symptoms in lupus
In the brain, a synapse (red – see diagonal “spine” across center of photo) is seen being wrapped around and attacked by immune cells called microglia (green), leading to synapse loss. Credit: Carroll lab / Boston Children’s Hospital

Up to 75 percent of patients with systemic lupus erythematosus — an incurable autoimmune disease commonly known as “lupus” —  experience neuropsychiatric symptoms.  But so far, our understanding of the mechanisms underlying lupus’ effects on the brain has remained murky.

“In general, lupus patients commonly have a broad range of neuropsychiatric symptoms, including anxiety, depression, headaches, seizures, even psychosis,” says Allison Bialas, PhD, a research fellow working in the lab of Michael Carroll, PhD, of Boston Children’s Hospital. “But their cause has not been clear — for a long time it wasn’t even appreciated that these were symptoms of the disease.”

Collectively, lupus’ neuropsychatric symptoms are known as central nervous system (CNS) lupus. Their cause has been unclear until now.

Perhaps, Bialas thought, changes in the immune systems of lupus patients were directly causing these symptoms from a pathological standpoint. Working with Carroll and other members of his lab, Bialas started out with a simple question, and soon, made a surprising finding – one that points to a potential new drug for protecting the brain from the neuropsychiatric effects of lupus and other diseases. The team has published its findings in Nature.

Read Full Story | 1 Comment | Leave a Comment

Flipping the switch on tumor growth

Pictures of angiogenic tumor cells
Time-lapse imaging can reveal tell-tale changes in cellular behaviors associated with tumor growth.

Without a blood supply, a tumor can remain dormant and harmless. But new blood vessel growth from an existing vessel, a process called angiogenesis, is a hallmark of both benign and malignant tumors. During angiogenesis, blood vessels invade tumors and activate them, fueling their growth.

Now, Marsha A. Moses, PhD, who directs the Vascular Biology Program at Boston Children’s Hospital, and members of her laboratory have revealed that a specialized imaging system can detect changes in cell behaviors. These changes predict when tumors are leaving a state of dormancy and becoming more likely to grow.

Read Full Story | Leave a Comment

Rare disease therapies: Three strategies to bridge the gap between research and industry

Rare disease research: DNA helix pictured here
Genetic mutations underpin many rare diseases.

Right now, there are about 7,000 rare diseases affecting 10 percent of Americans. Only five percent of these diseases have any FDA-approved treatment options.

Panelists:
David Williams, MD: President, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center; Senior VP, Chief Scientific Officer and Chief of Hematology/Oncology, Boston Children’s
Wayne Lencer, MD: Chief of Gastroenterology, Hematology and Nutrition, Boston Children’s
Phil Reilly, MD, JD: Venture Partner at Third Rock Ventures
Alvin Shih, MD, MBA: Chief Executive Officer at Enzyvant

Even at a place like Boston Children’s Hospital, where doctors regularly see children with rare diseases from all over the world, there are big challenges when it comes to drug discovery and treatment.

“Roughly 70 percent of drugs to treat children are used off-label,” says David Williams, Boston Children’s chief scientific officer. “That’s because these drugs were initially developed for adults and have not been tested formally in children.”

In order to cure rare diseases in children and adults, scientists must bridge the gap between research and industry. On May 25, Boston Children’s Technology and Innovation Development Office (TIDO) and MassBio held a candid panel discussion about what it will take to advance the development of rare disease therapies. Here are three of the biggest takeaways

Read Full Story | Leave a Comment

Precision drug delivery systems could ‘trigger’ an age of nanomedicine

Nanoscale drug delivery systems could target and destroy diseases in our body with increased precision and reduced side effects.

What if we could deliver biocompatible nanoparticles into the body and then activate them to release drugs exactly where they are needed, without causing side effects elsewhere?

Scientists like Daniel Kohane, MD, PhD, of Boston Children’s Hospital, are developing nanoscale drug delivery systems to do just that, using a variety of materials and triggers that are sensitive to a range of specific stimuli.

“Triggerable drug delivery systems could improve the treatment of many diseases by reducing side effects and increasing the effectiveness of therapeutics,” says Kohane, who directs the Laboratory for Biomaterials and Drug Delivery at Boston Children’s. He is the senior author on a recent article about the topic in Nature Reviews Materials.

One potential use of nanoscale drug delivery systems is of special interest to Kohane and his lab members

Read Full Story | Leave a Comment

Predicting influenza outbreaks faster with a digitally-empowered wearable device

Influenza viruses. Outbreaks can be predicted using digital health tools like Thermia.The Thermia online health educational tool, developed at Boston Children’s Hospital, has enabled one-month-faster prediction of seasonal influenza outbreaks in China, via its digital integration with a commercially-available wearable thermometer. The findings appear in a new study published in the American Journal of Public Health.

 “The fact that we were able to predict influenza outbreaks faster than China’s national surveillance programs really shows the capacity for everyday, wearable digital health devices to track the spread of disease at the population level,” says the study’s lead author Yulin Hswen, who is a research fellow in Boston Children’s Computational Epidemiology Group and a doctoral candidate at the Harvard T. H. Chan School of Public Health.

China has 620 million mobile internet users who can theoretically access the standalone Thermia application from any computer, smartphone or even the Amazon Alexa assistant.

Although the Boston Children’s team has previously demonstrated that social media can be used to track disease, this is the first time they’ve shown that outbreaks can be predicted through an integrated wearable device and online tool.

Read Full Story | Leave a Comment