This post is first in a series of profiles of researchers and innovators at Boston Children’s Hospital.
Martha Murray, Braden Fleming and their children in San Francisco.
“I’d like to meet the innovator who made the tricorder that Bones used on Star Trek,” says orthopedic surgeon Martha Murray, MD. “A push of the button and things healed, no muss, no fuss. I’d like to know how he or she made that work because I could really use one.”
Murray has been on a 30-year quest to devise a better way to treat anterior cruciate ligament (ACL) tears. She recently crossed a major milestone: The Food and Drug Administration approved a first-in-human safety trial of a bio-enhanced ACL repair that encourages the ligament to heal itself. Murray expects the first patients to enroll in the 20-patient trial by early 2015. We had a few questions for her.
Short snippets of DNA called aptamers (red) readily get into cancer cells (green and blue) on their own (left panel). They can't penetrate cells when stuck to an oligonucleotide (center), but regain the ability when the oligonucleotide's bonds are broken by UV light (right). (Images courtesy Lele Li, PhD.)
You have a drug. You know what you want it to do and where in the body you need it to go. But when you inject it into a patient, how can you make sure your drug does what you want, where you want, when you want it to?
The fact that childhood cancer is, thankfully, rare belies the fact that it is the leading cause of disease-related death in U.S. children age 1 to 19. The number of people with a direct stake in expanding research into pediatric cancer is quite large, well beyond the small number of children with cancer and their families. Not only are the life-long contributions of children cured of cancer enormous, but understanding cancers of young children could also hold the key to understanding a broad range of adult cancers. The time is ripe to allocate more resources, public and private, to research on pediatric cancer.
In an age of increased understanding of the genetic basis of diseases, one thing is striking about many childhood cancers. They are relatively “quiet” cancers, with very few mutations of the DNA. Young children haven’t lived long enough to acquire the large number of mutations that create the background “noise” associated with years of living. This makes it much easier to pinpoint the relevant genetic abnormalities in a young child’s cancer.
Add to this the growing realization that biology, including how various tumors use common “pathways,” is a major factor in how the cancer responds to treatment. Thus, a mechanism that’s relatively easier to observe in the cancers of young children could help scientists understand cancers in adults, in whom the same mechanism is hidden amid the clutter of mutations acquired over a longer life. Full story »
Teen science prodigy Jack Andraka, 17, addressed more than 300 summit attendees and shared his journey from Baltimore, Maryland high school freshman to developer of an early diagnostic test for pancreatic, ovarian and lung cancers. And he achieved this extraordinary task before getting his driver’s license.
After the loss of a close family friend to pancreatic cancer in 2010, Andraka, then 13, sought answers. Full story »
It’s increasingly clear that good health care is as much about communication as about using the best medical or surgical techniques. That’s especially true during the “handoff”—the transfer of a patient’s care from provider to provider during hospital shift changes. It’s a time when information is more likely to fall through the cracks or get distorted.
Subtract 68 from 100 to get a pulse pressure of 42 (Wikiphoto/Creative Commons)
Second in a two-part series on cardiovascular prevention in children. Read part 1.
Carrying too much weight is tough on the body. The dramatic rise of obesity in recent years means more and more people are confronting increased cardiovascular risk due to changes in their blood vessels, cholesterol levels, blood pressure, and blood sugar. And the problem isn’t limited to adults: Today, there are more than three times as many obese children in the U.S. than there were in the early 1970s.
However, not every person with excess weight has cardiac risk factors, and not everyone with cardiac risk factors carries excess weight. So what is the relationship between childhood obesity and cardiac risk factors later in life? What links excess weight to its consequences?
Justin Zachariah, MD, MPH, a cardiologist at Boston Children’s Hospital, was inspired to investigate these “risk factors of risk factors” when he observed a pattern in his pediatric preventive cardiology clinic. He noticed that many of his patients who were carrying excess weight did not have very high blood pressure, or hypertension. Full story »
First of a two-part series on cardiovascular prevention in children. Read part two.
As childhood obesity has increased over the past 30 years, so has pediatric hypertension, which now affects one in 20 children. However, 48 percent of children with high blood pressure (BP) are of normal weight; other risk factors include low birth weight, which has also increased in the past 30 years (more recently dipping slightly to about 8 percent of births).
While children with hypertension rarely develop diseases that adults do, such as myocardial infarction, heart failure and stroke, they are at risk for adult hypertension and early symptoms of heart disease. “Attacking pediatric hypertension is the next frontier in cardiovascular disease prevention,” says Justin Zachariah, MD, MPH, of the Department of Cardiology at Boston Children’s Hospital.
The Affordable Care Act’s mandate to identify elevated BP in children is expected to increase referrals for screening. But diagnosing pediatric hypertension through BP screening in the clinic can be problematic. In a recent study, Zachariah found that ambulatory BP monitoring (ABPM) with a take-home device is both effective and cost-effective—especially when done from the get-go. Full story »
CRISPR—a gene editing technology that lets researchers make precise mutations, deletions and even replacements in genomic DNA—is all the rage among genomic researchers right now. First discovered as a kind of genomic immune memory in bacteria, labs around the world are trying to leverage the technology for diseases ranging from malaria to sickle cell disease to Duchenne muscular dystrophy.
In a paper published yesterday in Cell Stem Cell, a team led by Derrick Rossi, PhD, of Boston Children’s Hospital, and Chad Cowan, PhD, of Massachusetts General Hospital, report a first for CRISPR: efficiently and precisely editing clinically relevant genes out of cells collected directly from people. Specifically, they applied CRISPR to human hematopoietic stem and progenitor cells (HSPCs) and T-cells.
“CRISPR has been used a lot for almost two years, and report after report note high efficacy in various cell lines. Nobody had yet reported on the efficacy or utility of CRISPR in primary blood stem cells,” says Rossi, whose lab is in the hospital’s Program in Cellular and Molecular Medicine. “But most researchers would agree that blood will be the first tissue targeted for gene editing-based therapies. You can take blood or stem cells out of a patient, edit them and transplant them back.”
The study also gave the team an opportunity to see just how accurate CRISPR’s cuts are. Their conclusion: It may be closer to being clinic-ready than we thought. Full story »
Dolly the sheep, the first mammalian example of successful somatic cell nuclear transfer. (Toni Barros/Wikimedia Commons)
We all remember Dolly the sheep, the first mammal to be born through a cloning technique called somatic cell nuclear transfer (SCNT). As with the thousands of other SCNT-cloned animals ranging from mice to mules, researchers created Dolly by using the nucleus from a grown animal’s cell to replace the nucleus of an egg cell from the same species.
The idea behind SCNT is that the egg’s cellular environment kicks the transferred nucleus’s genome into an embryonic state, giving rise to an animal genetically identical to the nucleus donor. SCNT is also a technique for generating embryonic stem cells for research purposes.
While researchers have accomplished SCNT in many animal species, it could work better than it does now. It took the scientists who cloned Dolly 277 tries before they got it right. To this day, SCNT efficiency—that is, the percent of nuclear transfers it takes generate a living animal—still hovers around 1 to 2 percent for mice, 5 to 20 percent in cows and 1 to 5 percent in other species. By comparison, the success rate in mice of in vitro fertilization (IVF) is around 50 percent.