Creative Minds: Designing Personalized Clinical Trials

Karina Davidson

Karina Davidson/Jörg Meyer

It might have been 25 years ago, but Karina Davidson remembers that day like yesterday. She was an intern in clinical psychology, and two concerned parents walked into the hospital with their troubled, seven-year-old son. The boy was severely underweight at just 37 pounds and had been acting out violently toward himself and others. It seemed as though Ritalin, a drug commonly prescribed for Attention Deficit Disorder, might help. But would it?

To find out, the clinical team did something unconventional: they designed for the boy a clinical trial to test the benefit of Ritalin versus a placebo. The boy was randomly assigned to take either the drug or placebo each day for four weeks. As a controlled study, neither clinical staff nor the family knew whether he was taking the drug or placebo at any given time. The result: Ritalin wasn’t the answer. The boy was spared any side effects from long term administration of a medication that wouldn’t help him, and his doctors could turn to other potentially more beneficial approaches to his treatment.

Davidson, now an established clinical psychologist at the Columbia University Irving Medical Center, New York, wants to take the unconventional approach that helped this boy and make it more of the norm in medicine. With support from a 2017 NIH Director’s Transformative Research Award, she and her colleagues will develop three pilot computer applications—or digital platforms—to help doctors conduct one-person studies in their offices.

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Helping People in Need of a Stem Cell Transplant

Hoggatt and Chou in the lab

Caption: Study co-authors Jonathan Hoggatt (r) and Bin-Kuan Chou (l) look through a microscope at a patient’s mobilized stem cells.
Credit: Lee Hopkins, OLP Creative

In certain people with cancer or other serious diseases, transplants of healthy adult stem cells can be lifesaving. But donating blood-forming stem cells is a bit more complicated than giving blood. For example, stem-cell donors most often undergo five days of injections to build up enough of those vital cells in the blood for donation.

Wouldn’t it be great if we could find a way to make the donation process easier? Such improvements are now on the horizon.NIH-funded researchers recently found that, at least in mice, a single injection of two complementary treatments can generate enough stem cells in 15 minutes [1]. What’s more, stem cells harvested in this way have qualities that appear to increase the odds of transplant success.

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Snapshots of Life: Growing Mini-Brains in a Dish

Brain grown in a lab dish

Credit: Collin Edington and Iris Lee, Department of Biomedical Engineering, MIT

Something pretty incredible happens—both visually and scientifically—when researchers spread neural stem cells onto a gel-like matrix in a lab dish and wait to see what happens. Gradually, the cells differentiate and self-assemble to form cohesive organoids that resemble miniature brains!

In this image of a mini-brain organoid, the center consists of a clump of neuronal bodies (magenta), surrounded by an intricate network of branching extensions (green) through which these cells relay information. Scattered throughout the mini-brain are star-shaped astrocytes (red) that serve as support cells.

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Adding Letters to the DNA Alphabet

semi-synthetic bacterium

Credit: William B. Kiosses

The recipes for life, going back billions of years to the earliest single-celled organisms, are encoded in a DNA alphabet of just four letters. But is four as high as the DNA code can go? Or, as researchers have long wondered, is it chemically and biologically possible to expand the DNA code by a couple of letters?

A team of NIH-funded researchers is now answering these provocative questions. The researchers recently engineered a semi-synthetic bacterium containing DNA with six letters, including two extra nucleotides [1, 2]. Now, in a report published in Nature, they’ve taken the next critical step [3]. They show that bacteria, like those in the photo, are not only capable of reliably passing on to the next generation a DNA code of six letters, they can use that expanded genetic information to produce novel proteins unlike any found in nature.

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Creative Minds: Taking Aim at Adverse Drug Reactions

Sherrie Divito

Sherrie Divito

As a practicing dermatologist, Sherrie Divito sees lots of patients each week at Brigham and Women’s Hospital, Boston. She also sees lots of research opportunities. One that grabbed her attention is graft-versus-host disease (GvHD), which can arise after a bone-marrow transplant for leukemia, lymphoma, or various other diseases. What happens is immune cells in the donated marrow recognize a transplant patient’s body as “foreign” and launch an attack. Skin is often attacked first, producing a severe rash that is a harbinger of complications to come in other parts of the body.

But Divito saw something else: it’s virtually impossible to distinguish between an acute GvHD-caused rash and a severe skin reaction to drugs, from amoxicillin to carbamazepine. In her GvHD studies, Divito had been researching a recently identified class of immune cell called tissue-resident memory T (Trm) cells. They remain in skin rather than circulating in the bloodstream. The clinical similarities made Divito wonder whether Trm cells may also help to drive severe skin allergies to drugs.

Divito has received a 2016 NIH Director’s Early Independence Award to find out. If correct, Divito will help not only to improve the lives of thousands of people with GvHD, but potentially benefit the millions of other folks who experience adverse reactions to drug.

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