Pain and itch may seem like quite different sensations, but they both start from the same place—a bundle of nerves at the base of the spine known as the dorsal root ganglion. At the Johns Hopkins University School of Medicine, neuroscientist Xinzhong Dong is uncovering the molecular and cellular basis of pain and itch, with an eye toward better treatments for chronic conditions involving these sensations.

Dong first began studying sensory biology as a postdoctoral fellow at the California Institute of Technology. Working with HHMI Investigator David Anderson, Dong was searching for genes expressed only in sensory nerves, expecting they would likely have important roles in those cells. This led him to a family of about 50 protein receptors known as Mrg receptors.

A few years later, as an HHMI early career scientist at Johns Hopkins, Dong began to uncover the functions of the Mrg proteins. He discovered that a subset of the receptors is involved in certain kinds of itch sensations, while other receptors appear to play a key role in reducing pain perception. Now, he’s trying to identify and describe the biochemical pathways involved in these sensations in hopes of finding new therapies.

Because the functions of many Mrg receptors appear to be related to pain and itch, Dong’s most recent discovery is something of an anomaly. He’s found an Mrg receptor that is sensitive to a variety of compounds—including components of animal venoms and therapeutic drugs—that trigger the immune system, suggesting the receptor could be at the root of many painful and dangerous allergic reactions to medications. Dong’s team is looking for compounds that could safely block the receptor in humans to prevent such drug allergies or at least lessen the drugs' side effects.

Although Dong, now an HHMI investigator, has uncovered the functions of many Mrg receptors, he’s only scratched the surface. There are still dozens of other Mrg genes to study, and other unknown functions waiting to be discovered.

Image: Steve Ruark

About the HHMI Investigator Program

HHMI investigators, appointed through rigorous competitions, are among the most creative and promising biomedical researchers in the United States. The scientists receive long-term, flexible support, enabling them to follow their own curiosity in the pursuit of significant biological questions. The Investigator Program is the Institute’s flagship program, with an annual commitment of over $600 million to support the investigators and their host institutions across the country. The collaboration between HHMI and these institutions powerfully extends the nation’s research capacity. Read more >>