Autoimmune disease happens when immune cells get confused and attack something they shouldn’t — for example, beta cells (cells that make insulin) in your pancreas in type 1 diabetes (T1D) or neurons (brain cells) in multiple sclerosis. A lot of autoimmune disease research is focused on slowing down the immune system cells that cause this attack. But Caroline Stefani, PhD, and Eddie James, PhD, are teaming up to ask a different question: Can we make beta cells more resilient so they survive the attack?

“We think about it like giving the cells a bulletproof vest or a survival pack,” Dr. Stefani says. “We want to see if there is a way — where even if the cells get attacked — we can make them more resilient so they can repair themselves or survive longer.”

Dr. Stefani is an expert in cell repair mechanisms and advanced imaging tools, while Dr. James is an expert in T1D. Together, they recently received an Innovation Fund award to combine two exciting approaches, in a study that could lay the groundwork for a completely new approach to treating autoimmune disease.

“BRI’s Innovation Fund gives us the opportunity to bring different skill sets together to work toward the same goal,” Dr. James says. “We’re combining our perspectives and techniques to answer a question that we could never answer alone.”

Tell us about your project. What is your team hoping to learn?

Dr. James: Broadly, we’re working to understand the behavior of pancreatic beta cells, which are cells that make insulin in your body. These are the cells that are targeted by the immune system and ultimately die off and lose their function in type 1 diabetes.

Historically, we were only able to study these cells through organ donors who have died and donated their pancreases to science. But now, we can grow these cells in a lab using a technique that Aisha Callebaut, PhD, a postdoc in my lab, learned from an expert group in Belgium.

Our project is getting the infrastructure in place to grow these cells at BRI. From there, Caroline will use a super powerful microscope which will enable us to answer questions about why these cells die and what could make them more resilient.

Dr. Stefani: I think about this work as making a mini pancreas in a dish. So Eddie’s team is actually creating that, and then I am leading the imaging. We will run different experiments where we genetically modify the cells and test different treatments to see if we can make them more resilient. The microscope will allow us to examine these cells in some really new and exciting ways including detailed 3D images and real-time videos.

Down the line, how do you hope this work will help predict, prevent, reverse and cure immune system diseases?

Dr. Stefani: I’m excited about our work because this is a very different approach to autoimmune disease research. We are building on one of my team’s previous findings where we identified a gene that seemed to make cells more resilient to the attack in autoimmune disease. This study will allow us to learn more about how this happens specifically in the context of type 1 diabetes.

If our idea of making cells more resilient works in pancreatic beta cells, this approach could be promising for other disease areas too. For example, could we make neurons more resilient to treat or prevent neurodegenerative diseases like multiple sclerosis?

How might other scientists at BRI eventually be able to use this approach?

Dr. Stefani: From the imaging side, we are developing methods to gather detailed information about which cells survive and how cells interact with the immune system and taking detailed 3D images. Once we have these methods in place, we could apply them to answer many different questions in many types of cells.

Dr. James: In terms of growing cells, we’ve actually started by making beta cells which are one of the hardest types of cells to make. They require seven steps, while skin cells, gut cells or neurons can be made with two or three steps. So, once we have the infrastructure in place to create these beta cells, we can create many other types of cells to study autoimmune diseases.

Why is philanthropy to support new research avenues and technologies important?

Dr. James: This funding is crucial to get the ball rolling on new technologies and early-stage research. Philanthropy is what we need to get the first tantalizing results that enable us to apply for larger grants. Part of this work is also bringing this technology to BRI to ask questions only BRI would ask or answer. There’s just a handful of other labs in the world making these beta cells, and getting this up and running at BRI really allows us to ask questions that are aligned with our mission and vision.

I was also on the selection committee for a past Innovation Fund award and it was so difficult to decide because there were so many interesting, exciting projects. Saying yes to one project means saying no to others, and a lot of these projects really deserve this funding. My hope in the future is that we can give more of these grants out each year and grow our capabilities even more. We're so excited to see this type of fund up and running at BRI, and we’re so grateful for everyone who has supported it.

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