From a series profiling researchers and innovators at Boston Children’s Hospital

He’s a big thinker focused on harnessing the hyper-small. Daniel Kohane, MD, PhD, is a leading drug delivery and biomaterials researcher, leveraging nanoparticle technology and other new vehicles to make medications safer and more effective.

It’s not quite what he had in mind as a child. He dreamed of studying life forms in remote galaxies.

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But when he became aware of the constraints of relativity, he re-focused his ambitions, ultimately concentrating on innovations in drug delivery. Here’s what he told us. Full story »

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“My biggest fear is that if I am not there to help him, when I wake him up he will be dead from seizures.”

That mother’s fear has a sound basis. The risk for sudden death from epilepsy, or SUDEP, is as high as 1 in 100 in the sickest children with epilepsy, says Tobias Loddenkemper, MD, of the Epilepsy Center at Boston Children’s Hospital. Many of those seizures occur in sleep.

Loddenkemper has been testing a novel wristband that uses motion and sweat sensors to detect the onset of a seizure—upon which the device would sound an alert. So far, the device has performed well on tests at Boston Children’s, picking up more than 90 percent of generalized tonic-clonic (grand mal) seizures, says Loddenkemper. But more work is needed to reduce false alarms (often generated when children are playing video games) and enable to device to spot more subtle seizures that are less convulsive in nature.

“This work is triggered by some very personal experiences of parents calling my office telling me their child died in sleep from seizures,” says Loddenkemper. “I dread these calls. We want to prevent those calls.”

The device manufacturer has created a fundraising site to help further the wristband’s development.

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Chromosome breaks translocations gene editing CRISPR TALENs ZFNs zinc fingers Frederick Alt

When chromosomes break, the ends can join together in a number of ways, some of which can cause trouble. A new QA method could help researchers avoid making problematic breaks when using gene editing technologies like CRISPR.

Labs the world over are jumping onto the gene editing bandwagon (and into the inevitable patent arguments). And it’s hard to blame them. As these technologies have evolved over the last two decades starting with the zinc finger nucleases (ZFNs), followed by transcription activator-like effector nucleases (TALENs) and CRISPR—they’ve become ever more powerful and easier to use.

But one question keeps coming up: How precise are these systems? After all, a method that selectively mutates, deletes or swaps specific gene sequences (and now can even turn genes on) is only as good as its accuracy.

Algorithms can predict the likely “off-target” edits based on the target’s DNA sequence, but they’re based on limited data. “The algorithms are getting better,” says Richard Frock, PhD, a fellow in the laboratory of Frederick Alt, PhD, at Boston Children’s Hospital. “But you still worry about the one rare off-target effect that’s not predicted but falls in a coding region and totally debilitates a gene.”

Frock, Alt (who leads Boston Children’s Program in Cellular and Molecular Medicine, or PCMM), fellow Jiazhi Hu, PhD, and their collaborators recently turned a method first developed in Alt’s lab for studying broken chromosomes into a quality assurance tool for genome editing. As a bonus, the method—called high-throughput genome translocation sequencing (HTGTS)—also reveals the “collateral damage” gene editing methods might create in a cell’s genome, information that could help researchers make better choices when designing gene editing experiments. Full story »

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Portal for beating heart surgery-analagous to mine entrance

When a patient needs a cardiac intervention, surgeons can choose to access the heart in one of two ways: open-heart surgery or a cardiac catheterization.

Open-heart surgery offers clear and direct access to the heart, but it also requires stopping the heart, draining the blood, and putting the patient on an external heart and lung machine. Catheterization—insertion of a thin, flexible tube through the patient’s groin and up into the still-beating heart—is less invasive. But it’s not suitable for very complicated situations, because it is hard to manipulate the heart tissue with catheter-based tools from such a far distance.

Both methods have been highly optimized, but each has its own risks, benefits and drawbacks. Wouldn’t it be nice if there were a way to directly access the heart and maintain normal heart function and blood flow while repairs are performed?

Nikolay Vasilyev, MD, thought so. A scientist in the cardiac surgery research lab at Boston Children’s Hospital, led by Pedro del Nido, MD, Vasilyev has designed a platform technology that may revolutionize the way we conduct cardiac interventions. Full story »

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Stem cell colony Wyss Institute James Collins George Daley complexity

Researchers discovered many small nuances in pluripotency states of stem cells by subjecting the cells to various perturbations and then analyzing each individual cell to observe all the different reactions to developmental cues within a stem cell colony. (Credit: Wyss Institute at Harvard University)

Stem cells offer great potential in biomedical engineering because they’re pluripotent—meaning they can multiply indefinitely and develop into any of the hundreds of different kinds of cells and tissues in the body. But in trying to tap these cells’ creative potential, it has so far been hard to pinpoint the precise biological mechanisms and genetic makeups that dictate how stem cells diverge on the path to development.

Part of the challenge, according to James Collins, PhD, a core faculty member at the Wyss Institute for Biologically Inspired Engineering, is that not all stem cells are created the same. “Stem cell colonies contain much variability between individual cells. This has been considered somewhat problematic for developing predictive approaches in stem cell engineering,” he says.

But now, Collins and Boston Children’s Hospital’s George Q. Daley, MD, PhD, have used a new, very sensitive single-cell genetic profiling method to reveal how the variability in pluripotent stem cells runs way deeper than we thought.

While at first glimmer, it could appear this would make predictive stem cell engineering more difficult, it might actually present an opportunity to exert even more programmable control over stem cell differentiation and development than was originally envisioned. “What was previously considered problematic variability could actually be beneficial to our ability to precisely control stem cells,” says Collins. Full story »

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Second in a series of videotaped sessions at Boston Children’s Hospital’s recent Global Pediatric Innovation Summit + Awards 2014.

Your first job as an innovator is to persuade your colleagues that playing it safe is the riskiest strategy of all, says Bill Taylor, Fast Company’s cofounder and founding editor. During his keynote address, “A Practically Radical Prescription for Health Care,” Taylor urged health care innovators to embrace change and look broadly to other fields–even the circus–for lessons.

He invoked what George Carlin called “vuja de”: The opposite of deja vu, it’s seeing a familiar thing in new way. “We learn and grow the most when we meet with people unlike us,” Taylor said.

Ask yourself, “What are we offering that is hard to come by?” Fill a need before other organizations even see it. It may be hidden in plain sight. Here’s Taylor’s talk in full:

Stay tuned as we post more sessions from the Pediatric Innovation Summit (also available on YouTube) and read our blog coverage.

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From a series on researchers and innovators at Boston Children’s Hospital

Improbable as it sounds, autism researcher Susan Faja, PhD, likens her job to improv. “I really like Tina Fey’s description of her days as an improv comedian,” says Faja, who joined Boston Children’s Hospital’s Laboratories of Cognitive Neuroscience in July 2014 as a research associate. “In improv, you have to say ‘yes’ to the lead handed to you by your partner and then add an ‘and’ with your own contribution. My research approach is similar. Understanding how a particular neural system is working provides a starting point. Designing a targeted intervention starting at that point is like saying, ‘yes, and…’”

Like an improv routine where new elements keep getting added, Faja loves to investigate how brain and behavior and research and clinical application can be combined. Currently, she is examining whether computer training can change brain responses and behavior in children with autism spectrum disorder.

She first investigates how neural responses correlate to symptoms of autism and then tests a targeted training, using electrophysiology to understand which aspects of brain and behavior it changes. Her work was recently recognized by the National Institutes of Health Career Development Award. Full story »

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Pain in a dish nociceptors

Neurons from patients could lead researchers to better drugs for chronic pain.

Chronic pain, affecting tens of millions of Americans alone, is debilitating and demoralizing. It has many causes, and in the worst cases, people become “hypersensitized”—their nervous systems fire off pain signals in response to very minor triggers.

There are no good medications to calm these signals, in part because the subjectivity of pain makes it difficult to study, and in part because there haven’t been good research models. Drugs have been tested in animal models and “off the shelf” cell lines, some of them engineered to carry target molecules (such as the ion channels that trigger pain signals). Drug candidates emerging from these studies initially looked promising but haven’t panned out in clinical testing. Full story »

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Paul Farmer, president and co-founder of Partners in Health, has dedicated his life to the idea that the problems of the world’s poorest people are humanity’s problems writ large. Having recently returned from West Africa, Farmer spoke at Harvard Medical School and appeared on the Colbert Report last week, calling for a stronger response to the Ebola outbreak.

“We want to have a radical inclusiveness,” Farmer told the Harvard Medical School audience. “We readily acknowledge that we are overwhelmed by this.” Full story »

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First in a series of videotaped sessions at Boston Children’s Hospital’s recent Global Pediatric Innovation Summit + Awards 2014.

Inspiration for pediatric innovation is everywhere—from hackathons to waiting rooms to research labs—but getting from concept to clinic is a challenge. This panel discussion offers observations, insights and strategies for success in pediatric health, from drug development to caregiver support:

Panelists:

Stay tuned as we post more sessions from the Pediatric Innovation Summit (also available on YouTube) and read our blog coverage.

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