Dr. Cate Speake is a Research Assistant Member at Benaroya Research Institute (BRI) at Virginia Mason, where she is investigating biomarkers for type 1 diabetes. She also plays a central role in BRI’s biorepositories, including being the Project Lead on a new project to profile the healthy immune system in partnership with the Allen Institute for Immunology. We sat down with Dr. Speake to discuss this partnership, and how it relates to the biorepositories at BRI.

BRI is well known for their extensive biorepository resources for the study of autoimmune diseases. What exactly is a biorepository, and how do researchers use it?

A biorepository is a collection of biological samples (such as blood or other tissue) gathered from a group of participants, and paired with a registry where the participants share their medical data and information. The collection provides scientists with samples and data to use in their research. For the remainder of this interview, I’ll be using the word “biorepository”, but what I really mean is the biorepository paired with the registry.

At BRI, our research focuses on the immune system and how it functions or malfunctions. It therefore shouldn’t be a surprise that all of our biorepositories are also related to the immune system. They were first created 20 years ago, and include samples from over 15,000 participants. These samples are used not just here at BRI, but by researchers around the world.

Specifically, what type of immune-related biorepositories does BRI have?

I’m involved in the BRI diabetes biorepository, but we also have well established biorepositories for studying other autoimmune diseases, including rheumatoid arthritis, lupus, multiple sclerosis, and inflammatory bowel disease. We more recently established a biorepository for studying Down syndrome, because people with Down syndrome are more frequently impacted by autoimmunity than the rest of the population, as well as a cancer biorepository, as we’re interested in understanding the role that the immune system plays in cancer. 

Can you provide an example of how a biorepository could be used by a researcher in a study?

Absolutely. Many of the researchers who are using our biorepositories are trying to understand the difference between immune health and immune disease. To allow for this type of research, we have a very active biorepository containing samples from people with healthy immune systems. A researcher here at BRI, Erik Wambre, published a cool study a couple of years ago where he accessed our biorepositories of individuals with allergies (pollen, dander, food, etc) and without allergies, and specifically got samples from various people at different times of the year (to account for the presence or absence of pollen).

Through this research, he identified a particular type of T helper cell that is broadly present in people with different kinds of allergies, but is almost entirely absent in people lacking allergies. He’s now studying these cells in more detail, but his original research was performed based on his ability to access these kinds of samples from a biorepository.

Stepping away from biorepositories for a moment, what is it that you study at BRI?

We study immune diseases at BRI, and type 1 diabetes (T1D) is the one that I’m most interested in. This form of diabetes occurs when the immune system attacks the insulin-producing cells of the pancreas, resulting in an inability to produce the hormone. Insulin is needed for all the cells of your body to uptake glucose, so people with T1D require insulin supplementation for the rest of their lives. The disease causes hyperglycemia, which can lead to long term complications, and hypoglycemia, which can lead to death. 

I’m interested in the discovery and validation of biomarkers related to T1D. Biomarkers are essentially anything that we can measure that tells us something about someone’s health. In the context of T1D, an existing biomarker is hemoglobin A1C, which can tell us what your glucose control looked like over the last three months. I run a large study that involves researchers across North America and Europe, who are all working together to try to discover biomarkers that can predict what’s going to happen to someone’s insulin secretion after they’re diagnosed with T1D. 

The reason for this interest is that at the time that a patient is diagnosed with T1D, they are likely still making some level of their own insulin. But there is variability in the amount they make, and the length of time that they continue to make it. Some patients will only produce insulin for one year after diagnosis, while others will still be producing it 50 years later. Knowing when insulin secretion will halt is important, because making even a small amount of your own insulin has been shown to be protective against some of the long-term complications associated with the disease. My goal is to identify biomarkers that can predict this.

Have you taken advantage of BRI’s biorepositories in your research?

Yes. In order to identify biomarkers, we are accessing samples from T1D patients enrolled in clinical trials, which include really well characterized clinical and metabolic measurements taken during the first couple of years after diagnosis. But in order to access those samples, I first asked that all the researchers participating in the study validate their assays using samples from the BRI biorepository, in order to demonstrate technical reproducibility. 

We’ve also been using the biorepositories to study biological reproducibility. In order for a biomarker to be a true biomarker, it needs to vary in the population. If it’s found in every person at the same level, then it doesn’t tell us anything. To test for possible biomarkers, we took biorepository samples from a cohort of people with varying ages, clinical characteristics, and other factors. If no variation in a particular substance is found in that population, it suggests that there probably isn’t any variation in the whole population, and we shouldn’t pursue it as a biomarker. So all the labs involved in this study measured their markers in the two different cohorts, and those samples came from the BRI biorepositories.

BRI has recently partnered with the Allen Institute for Immunology with the goal of creating a deeper understanding of the immune system. Can you describe this partnership? 

Absolutely. The goal of the Allen Institute for Immunology is to deeply understand the immune system in health and disease. They’re partnering with sites around the country to try and start that process by looking at the immune system in health from childhood all the way through to late adulthood. BRI’s biorepositories make us a logical partner in this initiative. 

Our role in this partnership is to specifically study healthy immune systems in more depth than has previously occurred. This is critically important, because without an understanding of a healthy system, it’s impossible to understand what has changed in a diseased system. We plan to expand our biorepository of individuals with healthy immune systems by increasing the data that we collect in our registry. We will start to include data on lifestyle and environmental factors (such as food intake, exercise, travel habits, etc.) in order to really understand what drives the variability that we’re sure to see throughout the duration of the project. The plan is to bring in people with healthy immune systems between 25-35 or 55-65 years of age for ten visits over two years. Our second goal is to use flu immunization as a way to understand the response of immune systems. These responses differ between individuals with healthy immune systems as well as individuals whose immune systems are being challenged by disease.  

It’s clear that BRI’s biorepositories have driven much of its success. If you were to launch a new biorepository, what would you want it to be?

That’s a good question. To be honest, I actually think that creating another biorepository is probably not the next thing we should focus on. Instead, we need to take what we’re starting to develop with the Allen Institute for Immunology partnership, and begin to expand it across all of our biorepositories. While we’ve been able to bring in people longitudinally through the context of various studies over time, making it something that we do routinely and consistently would really change the kinds of questions that we could answer. Analyzing lifestyle and environmental factors in our immunological analyses is something that should be extended to all our existing biorepositories as well. 

Thank you for taking the time to discuss your research with us, Dr. Speake! We wish you, BRI, and the Allen Institute for Immunology the best of luck in your partnership!