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.

Continue reading

Skin Health: New Insights from a Rare Disease

Forehead of study participant with rare form of ichthyosis

Courtesy of Keith Choate, Yale University School of Medicine, New Haven, CT

Skin is the largest organ in the human body, yet we often take for granted all of the wonderful things that it does to keep us healthy. That’s not the case for people who suffer from a group of rare, scale-forming skin disorders known as ichthyoses, which are named after “ichthys,” the Greek word for fish.

Each year, more than 16,000 babies around the world are born with ichthyoses [1], and researchers have identified so far more than 50 gene mutations responsible for various types and subtypes of the disease. Now, an NIH-funded research team has found yet another genetic cause—and this one has important implications for treatment. The new discovery implicates misspellings in a gene that codes for an enzyme playing a critical role in building ceramide—fatty molecules that help keep the skin moist. Without healthy ceramide, the skin develops dry, scale-like plaques that can leave people vulnerable to infections and other health problems.

Two patients with this newly characterized form of ichthyosis were treated with isotretinoin (Accutane), a common prescription acne medication, and found that their symptoms resolved almost entirely. Together, the findings suggest that isotretinoin works not only by encouraging the rapid turnover of skin cells but also by spurring patients’ skin to boost ceramide production, albeit through a different biological pathway.

Continue reading

Eczema Relief: Probiotic Lotion Shows Early Promise

Staphylococcus aureus bacteria

Caption: Scanning electron microscopic image of Staphylococcus aureus bacteria (orange).
Credit: CDC/Jeff Hageman, MHS

Over the years, people suffering from eczema have slathered their skin with lotions containing everything from avocado oil to zinc oxide. So, what about a lotion that features bacteria as the active ingredient? That might seem like the last thing a person with a skin problem would want to do, but it’s actually a very real possibility, based on new findings that build upon the growing realization that many microbes living in and on the human body—our microbiome—are essential for good health. The idea behind such a bacterial lotion is that good bugs can displace bad bugs.

Eczema is a noncontagious inflammatory skin condition characterized by a dry, itchy rash. It most commonly affects the cheeks, arms, and legs. Previous studies have suggested that the balance of microbes present on people with eczema is different than on those with healthy skin [1]. One major difference is a proliferation of a bad type of bacteria, called Staphylococcus aureus.

Recently, an NIH-funded research team found that healthy human skin harbors beneficial strains of Staphylococcus bacteria with the power to keep Staph aureus in check. To see if there might be a way to restore this natural balance artificially, the researchers created a lotion containing the protective bacteria and tested it on the arms of volunteers who had eczema [2]. Just 24 hours after one dose of the lotion was applied, the researchers found the volunteers’ skin had greatly reduced levels of Staph aureus. While further study is needed to learn whether the treatment can improve skin health, the findings suggest that similar lotions might offer a new approach for treating eczema and other skin conditions. Think of it as a probiotic for the skin!

Continue reading

Creative Minds: Interrogating a Master of Disguise

Monica Mugnier

Monica Mugnier

When I volunteered several years ago as a physician in a small hospital in West Africa, one of the most frustrating and frightening diseases I saw was sleeping sickness. Now, an investigator supported by the NIH Common Fund aims to figure out how this disease pathogen manages to evade the human immune system.

Monica Mugnier’s fascination with parasites started in college when she picked up the book Parasite Rex, a riveting, firsthand account of how “sneaky” parasites can be. The next year, while studying abroad in England, Mugnier met a researcher who had studied one of the most devious of parasites—a protozoan, spread by blood-sucking tsetse flies, that causes sleeping sickness in humans and livestock across sub-Saharan Africa.

Continue reading

Creative Minds: Stretching the Limits of Wearable Devices

Darren Lipomi

Darren Lipomi/ Credit: UC, San Diego

Whether it’s a pedometer dangling from a belt loop or a skin patch to monitor heart rate and hydration levels, wearable and mobile devices have become essential gear for many of today’s fitness minded. But Darren Lipomi, a nanoengineer at the University of California, San Diego, envisions even more impressive things to come for optimizing workouts and bringing greater precision to health care. Lipomi is helping to build a future of “stretchable electronics,” semiconducting devices that will more seamlessly integrate with the contours of our bodies, outside and even inside, to monitor vital signs, muscle activity, metabolic changes, and organ function—to name just a few possibilities.

Lipomi and his colleagues specifically want to create a new class of semiconducting polymer that has the mechanical properties of human skin. This transparent “electronic skin” will have a soft elasticity to conform to shape, sense contact, absorb blunt force, and even self heal when dinged. It will do all of this—and possibly more—while continuously and wirelessly performing its programmed health-monitoring function. To help Lipomi build this future of real-time health monitoring, he has been awarded a 2015 NIH Director’s New Innovator Award. This NIH award supports exceptionally creative new investigators who propose highly innovative projects with the potential for unusually high impact.

Continue reading