In the 1860s, when the first American transcontinental railway was built, the first step in the process was to send out an advance team of scouts to identify the best route. After the pathway was mapped, a team of workers arrived to clear the road bed by blasting rock and leveling the ground. Another group laid the tracks, and then the trains were able to proceed.

Building a railroad is an apt analogy for medical research. Before new therapies can be developed, basic scientists need to scout out a pathway for research. At Benaroya Research Institute at Virginia Mason (BRI), where basic researchers work hand-in-hand with clinical investigators, the mission is to understand diseases of the immune system and find new therapies. Therefore, basic research at BRI is centered on this question: How does the immune system work? 

While scientific technology and knowledge of human diseases have exploded in the last several decades, the immune system is incredibly complex and hard to map. It has evolved redundant pathways over millennia in response to diverse challenges such as infections and viruses. Its random design can be prone to mistakes causing diseases of the immune system. Scientists have also learned there are multitudes of different immune system cell types, and few are exactly alike.

“The scientists in this field are extremely creative and have to have a long-term view of where they are headed,” says Dr. Nepom. “They are rewarded when they get to experience the incredible excitement of discovering something new that was previously unknown.”

Basic research in immunology at BRI is led by Steven Ziegler, PhD, program director. Major discoveries by BRI scientists and their teams in this field include the following:  

• Identification of genetic markers for disease susceptibility, particularly type 1 diabetes and rheumatoid arthritis. — Gerald Nepom, MD, PhD, and Barbara Nepom, MD.

• Descriptions of immune system genes, which provide insight into the way the immune system evolves and functions. — Steven Ziegler, PhD.

• Identification of a triggering molecule that promotes asthma and other allergic diseases. — Steven Ziegler, PhD.

• Discovery of ways the immune system cells cooperate and work together to fight infections while preventing immune attack against the body. — Adam Lacy-Hulbert, PhD.

• Descriptions of how the immune system turns on and off. — Daniel Campbell, PhD.

• Discovery of a “mirror” regulatory T cell that tells each different helper T cell how to respond. — Daniel Campbell, PhD.

• Identification of a subset of immune system cells believed to be potent inducers of multiple sclerosis and other diseases. — Estelle Bettelli, PhD.

• Definition of how external signals can react with immune system cells to change cell pathways. — Jessica Hamerman, PhD.

• Creating a topographical map of the molecular surface that initiates specific immune activation. — William Kwok, PhD, and Gerald Nepom, MD, PhD.