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

DNA and the Roots of Hair Roots

An Asian family (adult male and female and two adolescents, male and female) sitting around a coffee table playing a board game

Researchers have discovered one genetic recipe for this family’s thick dark hair.
Source: National Cancer Institute, NIH; Bill Branson, photographer.

It’s intriguing to find the roots of physical traits: skin color, height, and those weird tufts of hair on Uncle Mike’s ears. We’re all curious to know why we look the way we do. But new technologies are allowing us to discover the precise genetic roots of human traits that vary across the world. Variations in our DNA have helped us resist diseases and adapt to different climates and foods, enabling us to colonize just about every environment on the planet.

Recent studies have pinpointed variations responsible for lighter skin in Northern climates (such as SLC24A5 [1]) and the ability to tolerate milk sugar (lactose) in adulthood [2]. But a new NIH-funded study of a gene variant that arose in China adds a fascinating wrinkle—the use of a mouse model to help understand a potential human advantage [3]. (Regular readers will note that last week in this space I wrote about how mouse models could sometimes be misleading—this week the mouse is a champion!)

Continue reading