VCU researcher awarded NIH grant for study of mast cells

By Sathya Achia Abraham and Anna Goroncy

A Virginia Commonwealth University biology professor has received a $1.5 million National Institutes of Health grant to study the production and survival of mast cells, which are known to play a central role in asthma and allergy.

The work being conducted by John Ryan, Ph.D., associate professor in the Department of Biology, and colleagues may one day point researchers to new therapeutic strategies for the treatment or prevention of asthma and allergy, and inflammatory conditions such as rheumatoid arthritis, multiple sclerosis and heart disease.

Specifically, the five-year grant will allow Ryan's team to study how Interleukin-10 (IL-10) regulates mast cell production and survival. IL-10 is a cytokine, a type of signaling protein, which is well-known for being anti-inflammatory. IL-10 may be a key link in the body's normal dampening of potentially dangerous immune responses to prevent chronic disease, such as asthma, he said.

"This work should allow us to understand the basic way in which mast cells are normally regulated to prevent anaphylaxis and asthma in normal people," Ryan said. "IL-10 has also shown positive use in clinical trials, so we may be able to use it in therapeutic interventions once it's better understood."

Mast cells are packed with granules containing histamine and are present in nearly all tissues except blood. When mast cells are activated, inflammatory substances such as histamine, heparin and a number of cytokines are rapidly released into the tissues and blood, promoting an allergic response.

Ryan and his colleagues will conduct multiple in vivo and in vitro studies in mice to study IL-10's role in mast cell regulation. One of these studies involves a hookworm infection, Nippostrongylus brasiliensis, a pathogen similar to the hookworms that infect humans. Hookworms infect the intestines and cause abdominal pain, diarrhea, weight loss and loss of appetite. On the molecular level, the infection causes a huge mast cell response and an increase in the number of mast cells. As the body heals the infection, all those mast cells disperse.

The studies conducted by Ryan's team will include collaboration with Chris Kepley, Ph.D., and Larry Schwartz, M.D., Ph.D. in the VCU Department of Internal Medicine.

"VCU is a great climate to do this work because we have access to so many collaborators," Ryan said. He also collaborates with Sarah Spiegel, Ph.D., in the Department of Biochemistry and Dan Conrad, Ph.D., in the Department of Biochemistry.