Four health projects at Boston Childrens Hospital that could help adults – The Boston Globe

Read on for a sampling of adult-oriented research at Boston Childrens.

From the beginning, our brains are constantly reinventing themselves, pruning and sculpting their circuitryor synapsesin an effort to stay healthy and up to date.

That developmental process depends on cells called microgliathe Pac-Man of the brain, as Beth Stevens, an expert in neurocircuitry at Boston Childrens, calls them. Microglia hunt for the complement proteins that mark infected cells and extra synapses, gobbling up the bad or unnecessary stuff and making room for new connections.

But in the brains of people with Alzheimers disease, things go horribly wrong. Too many synapses are lost at the wrong time. So Stevens wondered if something might be triggering the microglia to destroy connections when they are still needed.

Stevens, who has been at Boston Childrens for 11 years, receives funding from the hospital, the NIH, and other sources, including as one of about 300 Howard Hughes Medical Institute investigators funded by the foundation. Her groundbreaking research also earned her a 2015 MacArthur genius grant.

While scientists dont yet know the initial trigger for inappropriate synaptic loss in humans, research in animal models has found that blocking the Pac-Man action of the microglia offers some protection, Stevens says. Meanwhile, studies show that there seems to be an abundance of activated microglia in some peoples brains.

That is changing the game in the sense that now these cells are thought to be potentially, not just a secondary player downstream, but they may even be causal, she says. And so now the big question is: OK, how do we figure this out? How are they contributing to Alzheimers, and in what ways are they doing this?

> Related: For more on Boston Childrens 150th anniversary, click here.

What if you were a pediatric infectious disease and vaccine expert, married to the director of a leading substance abuse and addiction program for adolescents? Would the two of you form a team? Two Boston Childrens doctors are doing just that, to develop a vaccine that could stop people from overdosing on opioids.

This would be a vaccine you give to somebody who has a known opioid-use disorder, or OUD, and is trying to get off but is at risk of overdosing, says Dr. Ofer Levy, who suggested the idea to his wife, Dr. Sharon Levy.

The couple teamed up with other doctors and researchers and won a $2.3 million NIH grant. Joining them from Boston Childrens are David Dowling, an immunologist and vaccinologist and instructor in pediatrics; and Elissa Weitzman, an associate professor at Harvard and an expert in approaching disease through the connection of biological, psychological, and sociological factors. They also work with the Inimmune Corp., based in Montana, and scientists at the University of Houston. (Two of their Houston collaborators, Therese and Thomas Kosten, are also married.)

As director of the hospitals precision vaccine program, Ofer Levy studies ways to develop vaccines for specific demographics. Hes also an expert in how to boost the immune response of a vaccine using adjuvantssmall molecules added to create a better immune response.

The ideal opioid vaccine would create an antibody response, blocking an overdose of heroin or fentanyl from getting from the blood into the brain and from suppressing breathing. But so far, trial opioid vaccines have not created strong enough antibody responses. Thats where our adjuvants come in, Levy says, adding that the trick is to find the right one to boost the vaccine and create long-lasting immunity.

The NIH grant allows the team to model the immune response of opioid users ages 15 to 30 by using blood samples from volunteers in the adolescent substance use and addiction program directed by Sharon Levy.

Meanwhile, Weitzman, whom Ofer Levy describes as one of the worlds experts on qualitative research, will do comprehensive interviews with patients and families about opioid abuse, medical interventions for addiction, and their expectations or attitudes regarding a vaccine. So were looking at precision at every level, Ofer Levy says.

While other sites also are working on an opioid vaccine, he says the Boston Childrens researchers are a powerful group because they are the only ones modeling the immune system outside the body, as well as creating adjuvant and vaccine models using blood from opioid users. Perhaps, he says, those tools will point the way to the right kind of vaccine.

Marsha Moses, the director of the vascular biology program at Boston Childrens, has a potent weapon in the fight against cancer: a world-class collection of urine.

Its part of her hunt for noninvasive biomarkers that could help with cancer detection and diagnosis, and monitoring treatment. She hopes the work leads to simple tests to detect breast and other cancers, such as brain cancers that currently may not be identified until they are symptomatic.

Urine is the perfect type of liquid biopsy, as we call it, for children as well as for adults, says Moses, also a professor at Harvard Medical School. Theres studies that show that people are much more compliant with a test if the test doesnt hurt. Also, urinary biomarkers would mean fewer children would need imaging that requires anesthesia, which carries its own inherent risk.

Moses lab, which receives support from the NIH, foundations, and philanthropic organizations, looks at how cancer affects an individuals protein profile, or proteome, and compares the presence of these proteins in urine samples. The researchers have identified a number of proteins that were different in healthy women compared with those of women who had various stages of breast cancer.

Researchers must validate, validate, validate the results in large cohorts, and thats resulted in her biorepository of thousands of urine samples from cancer patients, classed by gender, age, and health. Many markers are now being tested in trials.

In time, Moses hopes to make cancer screening and monitoring more available and economical, particularly for people without easy access to testing. Achieving that, she says, would be a huge contribution.

Even before he was the hospitals innovation leader, John Brownstein ran a research lab at Boston Childrens that studies how big data and new technologies can be used to improve our understanding of infectious diseases and their spread. He also has long been interested in how climate change affects disease-spreading insects such as ticks and mosquitoes.

The result is HealthMap.org, created partly with $3 million from Google, which uses crowd sourcing and machine-learning techniques to track the spread of illnesses worldwide: food poisoning, Ebola, West Nile, Zika, even the march of Eastern equine encephalitis across New England. The website and mobile app alert officials and help trace outbreaks. We have a huge volume of people across the globe that are using it, Brownstein says, from public health officials to clinicians.

Hes also brought mapping to consumers. FluNearYou.org tracks flu symptoms and outbreaks, and Vaccinefinder.org, developed with help from the federal government, lists nearby locations to get vaccines, such as for the flu and shingles, and how much they cost, as reported by the vendor.

Part of the point is to make immunization more accessible and acceptable, sometimes by using social media to combat misinformation. Its not like people are necessarily opposed to getting immunizations, Brownstein says, but they just dont find it convenient.

One of the drivers for Brownsteins work is climate change. He did his doctoral thesis on how changing climate affects the expansion of Lyme disease across North America. And so thats why its so important to improve our ability to monitor and survey these diseases, so we can enact public health interventions, he says, and also think about vaccine development.

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Four health projects at Boston Childrens Hospital that could help adults - The Boston Globe