Creative Minds: Helping More Kids Beat Anxiety Disorders

Dylan Gee

Dylan Gee

While earning her Ph.D. in clinical psychology, Dylan Gee often encountered children and adolescents battling phobias, panic attacks, and other anxiety disorders. Most overcame them with the help of psychotherapy. But not all of the kids did, and Gee spent many an hour brainstorming about how to help her tougher cases, often to find that nothing worked.

What Gee noticed was that so many of the interventions she pondered were based on studies in adults. Little was actually known about the dramatic changes that a child’s developing brain undergoes and their implications for coping under stress. Gee, an assistant professor at Yale University, New Haven, CT, decided to dedicate her research career to bridging the gap between basic neuroscience and clinical interventions to treat children and adolescents with persistent anxiety and stress-related disorders.

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Stem Cell Research: New Recipes for Regenerative Medicine

Cartilage and bone formation from stem cells

Caption: From stem cells to bone. Human bone cell progenitors, derived from stem cells, were injected under the skin of mice and formed mineralized structures containing cartilage (1-2) and bone (3).
Credit: Loh KM and Chen A et al., 2016

To help people suffering from a wide array of injuries and degenerative diseases, scientists and bioengineers have long dreamed of creating new joints and organs using human stem cells. A major hurdle on the path to achieving this dream has been finding ways to steer stem cells into differentiating into all of the various types of cells needed to build these replacement parts in a fast, efficient manner.

Now, an NIH-funded team of researchers has reported important progress on this front. The researchers have identified for the first time the precise biochemical signals needed to spur human embryonic stem cells to produce 12 key types of cells, and to do so rapidly. With these biochemical “recipes” in hand, researchers say they should be able to generate pure populations of replacement cells in a matter of days, rather than the weeks or even months it currently takes. In fact, they have already demonstrated that their high-efficiency approach can be used to produce potentially therapeutic amounts of human bone, cartilage, and heart tissue within a very short time frame.

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Snapshots of Life: Making the Brain Transparent

Brain webs

Credit: Ken Chan and Viviana Gradinaru Group, Caltech

What you are looking at above is something scientists couldn’t even dream of imaging less than a decade ago: bundles of neurons in the brainstem of an adult mouse. These bundles are randomly labeled with various colors that enable researchers to trace the course of each as it projects from the brainstem areas to other parts of the brain. Until recently, such a view would have been impossible because, like other organs, the brain is opaque and had to be sliced into thin, transparent sections of tissue to be examined under a light microscope. These sections forced a complex 3D structure to be visualized in 2D, losing critical detail about the connections.

But now, researchers have developed innovative approaches to make organs and other large volumes of tissue transparent when viewed with standard light microscopy [1]. This particular image was made using the Passive CLARITY Technique, or PACT, developed by the NIH-supported lab of Viviana Gradinaru at the California Institute of Technology (Caltech), Pasadena. Gradinaru has been working on turning tissues transparent since 2010, starting as a graduate student in the lab of CLARITY developer and bioengineering pioneer Karl Deisseroth at Stanford University. PACT is her latest refinement of the concept.

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International “Big Data” Study Offers Fresh Insights into T2D

World map

Caption: This international “Big Data” study involved hundreds of researchers in 22 countries (red).

It’s estimated that about 10 percent of the world’s population either has type 2 diabetes (T2D) or will develop the disease during their lives [1]. Type 2 diabetes (formerly called “adult-onset”) happens when the body doesn’t produce or use insulin properly, causing glucose levels to rise. While diet and exercise are critical contributory factors to this potentially devastating disease, genetic factors are also important. In fact, over the last decade alone, studies have turned up more than 80 genetic regions that contribute to T2D risk, with much more still to be discovered.

Now, a major international effort, which includes work from my own NIH intramural research laboratory, has published new data that accelerate understanding of how a person’s genetic background contributes to T2D risk. The new study, reported in Nature and unprecedented in its investigative scale and scope, pulled together the largest-ever inventory of DNA sequence changes involved in T2D, and compared their distribution in people from around the world [2]. This “Big Data” strategy has already yielded important new insights into the biology underlying the disease, some of which may yield novel approaches to diabetes treatment and prevention.

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Scoliosis Traced to Problems in Spinal Fluid Flow

Zebra fish model for scoliosis study

Caption: Normal zebrafish (top left) and a normal skeleton (bottom left); zebrafish with scoliosis (top right) and an abnormal scoliotic skeleton (bottom right).
Credit: Grimes DT, Boswell CW, Morante NF, Henkelman RM.

Many of us may remember undergoing a simple screening test in school to look for abnormal curvatures of the spine. The condition known as adolescent idiopathic scoliosis (IS) affects 3 percent of children, typically showing up in the tween or early teen years when kids are growing rapidly. While scoliosis can occur due to physical defects in bones or muscles, more often the C- or S-shaped spinal curves develop for unknown reasons. Because the basic biological mechanisms of IS have been poorly understood, treatment to prevent further progression and potentially painful disfigurement has been limited to restrictive braces or corrective surgery.

Now, in work involving zebrafish models of IS, a team of NIH-funded researchers and their colleagues report a surprising discovery that suggests it may be possible to develop more precisely targeted therapeutics to reduce or even prevent scoliosis. The team’s experiments have, for the first time, shown that mutation of a gene associated with spinal curvature in both zebrafish and humans has its effect by altering the function of the tiny hair-like projections, known as cilia, that line the spinal cord. Without the cilia’s normal, beating movements, the fluid that bathes the brain and spinal cord doesn’t flow properly, and zebrafish develop abnormal spinal curves that look much like those seen in kids with scoliosis. However, when the researchers used genetic engineering to correct such mutations and thereby restore normal cilia function and flow of cerebral spinal fluid (CSF), the zebrafish did not develop spinal curvature.

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