BENAROYA RESEARCH INSTITUTE AT VIRGINIA

Studying down syndrome and type 1 diabetes (t1d) to understand how autoimmune diseases startin october 2023, bri received the immune drivers of autoimmune disease (idad) grant. This study is examining people at higher risk for developing autoimmune diseases those with down syndrome (ds) and those with autoantibodies for type 1 diabetes (t1d) to better understand how and why autoimmune diseases develop. This work builds on previous findings from bernard khor, md, phd, which found that individuals with ds experience premature immune aging and are significantly more likely to develop conditions like autoimmunity and infections. The idad grant will support a multidisciplinary effort led by bri scientists to identify the genetic, molecular, and environmental factors that drive autoimmune disease progression. Researchers will compare immune profiles of individuals with ds with those at risk for t1d to uncover common mechanisms of immune dysfunction. The study will draw from bri's extensive biorepositories, providing a valuable resource for advancing knowledge in this field. This research has the potential to inform new treatments and prevention for autoimmune diseases in people with and without ds.

Understanding how lupus starts and progressesscientists have long known that an antibody called igg plays a big role in lupus. But bri's hayley waterman, phd, wanted to know - do other antibodies play a role in lupus too? She launched a study examining whether an antibody called iga may also play a role. She found that iga played a small role in lupus. But when she tested iga and igg together, she found a much bigger immune system response than either antibody acting alone. Dr. Waterman's findings could lead to breakthroughs in both diagnosing and treating lupus. Lupus is often difficult to diagnose because it has a wide range of symptoms that often come and go. And currently available treatments don't work equally well for everyone. So research into signs of iga and igg working together - and finding ways to disrupt that - holds tremendous promise for advancing care for this debilitating disease.after this initial finding, dr. Waterman and her mentor, jessica hamerman, phd, received significant nih funding to further explore these findings. They plan to study exactly how iga and igg work together to cause this significant immune system response in lupus. They're also interested in studying whether the presence of iga might explain why lupus can have such a wide array of symptoms. Lupus can cause everything from a skin rash to arthritis to kidney and lung problems, but scientists don't fully understand why it affects people in different ways. The research team wants to find out if iga is associated with certain symptoms or more severe disease.clinical research program bri oversees the clinical research program at virginia mason medical center, uniquely combining the expertise of a world-renowned medical research institute with the care of a healthcare quality leader. The clinical research program supports virginia mason clinical investigators in studies across a wide variety of autoimmune and immune-mediated diseases and conditions, as well as a broad range of other diseases such as cancer and cardiac disease. The clinical research program staff annually enrolls approximately 2,264 study participants into virginia mason trials.innovation fund awardestablished in 2023, the innovation fund award is given twice a year to internal recipients at bri. The objective is to facilitate development and implementation of new technologies that will advance work across our institution, through the funding of collaborative projects. Each award is funded by philanthropy. Bri's regular track and research track faculty are award eligible. Projects are required to include two or more bri faculty and address innovations useful to multiple research groups within the institute. Further, it is required that the protocols and results generated in the project will be made available to all bri investigators. At the end of 2023, eddie james, phd, and caroline stefani, phd, earned an innovation fund grant to combine two groundbreaking technologies: lab-grown human beta cells and a state-of-the-art microscope. Beta cells are pancreas cells that the immune system attacks in t1d. Previously, the only way to study these cells was if someone died and donated their body to science. In 2023, bri's aisha callebaut, phd, traveled to belgium to learn a new way to access these cells: growing them from human beta cells. The innovation fund grant supported the implementation of tools and technology needed to grow these cells at bri. Now, drs. James and stefani are examining these lab-grown cells to better understand why immune system cells attack beta cells in t1d and how they might make beta cells more resilient to that attack. This technique and infrastructure can also be used to engineer other types of immune cells - from neurons, to skin cells to gut cells - opening the door to answer new and important questions about a wide variety of diseases. In 2024, bri president jane buckner, md, and oliver harrison, dphil, earned an innovation fund grant to implement new methods of genome engineering in human t cells and mice, using crispr/cas9 and adeno-associated virus technology. This collaboration between the harrison and buckner labs aims to create advanced models for studying autoimmune disease.dr. Buckner's team will engineer human t cells by reintroducing t cell receptor sequences, allowing researchers to study autoreactive t cells. Meanwhile, dr. Harrison's group will develop new transgenic mouse models, including mice with b cell receptors that recognize bacterial antigens. These innovative approaches will enhance bri's ability to study immune response, improve disease models, and better understand the role of b and t cells in autoimmunity.