Benaroya Research Institute at Virginia Mason (BRI) is relatively small compared to large research universities, but its impact goes well beyond its size and location, accelerating scientific discovery globally. A key reason for this is BRI’s “culture of collaboration,” which expands the impact of scientists’ work through engagement with numerous external investigators. This article illustrates this collaborative emphasis with a few examples of how BRI’s expertise and unique scientific resources are shared with researchers all over the world.

“In many cases these collaborations result in extended scientific interactions that strengthen both BRI and our collaborating scientists,” says BRI Associate Director Jane Buckner, MD. “It helps us move research forward.”

Studying cells to eliminate allergies

Bill Kwok, PhD, and Erik Wambre, PhD, with Imperial College London

For a project on one of the major causes of allergies (Timothy grass), supported by the National Institutes of Health (NIH) and the Immune Tolerance Network, Drs. Kwok and Wambre at BRI work with Dr. Stephen Durham of Imperial College London. Clinical research participants in allergy studies in London contribute blood samples that are shipped to BRI for analysis. “By studying the immune profiling of these cells, we expect to learn more about the cellular and molecular mechanisms that lead to successful immunotherapy,” according to Dr. Kwok. This would allow researchers to find better ways to turn off the immune systems’ reaction to allergens and eliminate allergies.

Understanding T1D progression

Helena Reijonen, PhD, and Bill Kwok, PhD, with University of Helsinki and University of Turku

In an NIH funded project to better understand genetic susceptibility of type 1 diabetes, Drs. Reijonen and Kwok at BRI work with Dr. Mikael Knip at the University of Helsinki and Dr. Jorma Ilonen at the University of Turku, Finland. Finland has a universal health system with excellent medical records. The country is able to track the diagnosis and health history of every child in the country who develops type 1 diabetes, as well as their siblings. Samples from these children are sent from Finland to BRI for tetramer analysis—a technology developed at BRI to study the cellular properties of the immune system. This is helping scientists to understand how the disease progresses before symptoms begin to appear. With this knowledge, scientists can figure out how to stop the immune system from attacking insulin-producing cells in type 1 diabetes.

Immune Cells and Skin Diseases

Adam Lacy-Hulbert, PhD, and University of Rochester

“Using models of immune responses in the skin, developed by Dr. Deb Fowell at the University of Rochester, we have together discovered that immune cells use different mechanisms to enter inflamed and normal skin,” reports BRI’s Dr. Lacy-Hulbert. “This may lead to new approaches to block autoimmune diseases that cause skin disease (such as psoriasis, pemphigus and lupus) without affecting normal immune responses.” The Lacy-Hulbert Laboratory has a number of collaborations to advance research into how the immune system balances defenses against infections while preventing autoimmune diseases.

Cellular therapy and T1D

Steve Ziegler, PhD, and Jane Buckner, PhD, with University of California, San Francisco (UCSF) and Yale University

As part of a consortium funded by JDRF, Drs. Ziegler and Buckner at BRI collaborate with Dr. Jeff Bluestone at UCSF and Dr. Kevan Herold at Yale to study regulatory T cells in type 1 diabetes (T1D). Regulatory cells are important for modulating the immune system. Studies focus on ways to modify these cells for use in cellular therapy. In clinical trials, regulatory T cells are injected into a patient to increase suppression of an immune system’s attack on the cells that create insulin. Techniques for growing and modulating these cells are jointly developed, and methods specifically developed at BRI for monitoring the cells infused into patients are used in the trial.

Cellular Stress and T1D

Eddie James, PhD, and University of Pittsburgh

“In collaboration with Drs. Jon Piganelli and Meghan Marre at the University of Pittsburgh, we’re investigating cellular stress and the formation of disease,” explains BRI’s Dr. James. Cellular stress happens when target cells—such as islet beta cells in type 1 diabetes—mistakenly come under attack by the immune system or infectious agents. How the cells respond to this stress can have a major influence on whether the cells will survive. Dr. Piganelli is an expert in cellular stress and the impact it has on immune system diseases. The James Laboratory at BRI links this type of cellular stress to specific changes in the immune system that appear to be an important step in understanding how the body attacks its own islet beta cells causing type 1 diabetes.

Translating research to therapies

Jane Buckner, MD, and Gerald Nepom, MD, PhD, with Bio Design Institute at Arizona State University

When Drs. Jason LaBaer and Ji Qiu of the Bio Design Institute designed a new technology to identify autoantibodies—molecules made by the immune system that can act as biomarkers for disease—they approached Drs. Buckner and Nepom at BRI to translate this technology into medical applications. Starting with rheumatoid arthritis, and now extending these studies to relapsing polychondritis, this technology has uncovered several new potentially important molecular targets. Based on these data, the BRI lab of Dr. Eddie James is now investigating whether T cells from people with rheumatoid arthritis recognize these same molecules and could be used as targets for new therapies.

Hub for immune research networks

Carla Greenbaum, MD, Gerald Nepom, MD, PhD, Eddie James, PhD, Jared Odegard, PhD, and Jane Buckner, MD

BRI investigators lead two of the major autoimmune disease clinical networks, both funded by NIH. TrialNet (Dr. Greenbaum) and the Immune Tolerance Network (Dr. Nepom) involve dozens of academic medical centers worldwide. BRI also acts as the coordinating center for other major collaborative initiatives such as the JDRF Core for Assay Validation (Dr. Odegard), the Immunology of Diabetes Society T Cell Workshop (Dr. James) and the NIH-sponsored Cooperative Disease Study Group for Autoimmunity (Dr. Buckner).