Shana Kelley: Instrumented Tissues for Monitoring Human Body in Real-Time

Jonathan D. Grinstein, PhD, North American Editor of Inside Precision Medicine, hosts a new series called Behind the Breakthroughs that features the people shaping the future of medicine. With each episode, Jonathan gives listeners access to his guests’ motivational tales and visions for this emerging, game-changing field.

Shana Kelley, PhD, is unafraid to tackle ambitious scientific challenges—concepts that might seem drawn from science fiction. For example, she envisions technologies that could monitor immune system activity in patients in real time, much like a glucose monitor tracks blood sugar levels. Transforming such a vision into a clinically viable and practical technology is a formidable task. It demands interdisciplinary expertise spanning chemistry, biology, engineering, and computer science. It also requires flexible financial support beyond the constraints of traditional government funding, and it calls for strong, visionary leadership.

An acclaimed scientist, inventor, and entrepreneur, she has earned numerous prestigious awards, holds over 50 patents, founded four biotech companies, and serves in leadership roles across major journals and research initiatives in nanomedicine and regenerative medicine. Kelley is the Neena B. Schwartz Professor at Northwestern in the departments of chemistry, biomedical engineering, and biochemistry & molecular genetics, as well as the president of the Chan Zuckerberg Biohub Chicago. At the Biohub, she is developing what she describes as “instrumented tissues”—advanced technologies designed to measure biological processes within human tissues at a precise, molecular level. In this episode of Behind the Breakthroughs, Kelley discusses her career path, shaped by her passion for making the invisible visible, and provides insight into the innovative work underway at the Chan Zuckerberg Biohub Chicago.

This interview has been edited for length and clarity.

IPM: What are you working on at the CZ Biohub Chicago?

Kelley: At the Biohub, we’re pursuing new technologies that allow us to study inflammation, and if you really dig into the literature and try to understand how dysregulated T cells contribute to different types of autoimmune disease or how they contribute to chronic inflammation, you’ll quickly realize there are a lot of open questions. We don’t know how immune cells get off track and start doing bad things inside the body. We have bits and pieces of information, but we don’t really understand or have a complete picture. That’s a big question: How do immune cells become dysregulated, and what exactly causes inflammation? So we’re developing platforms and technologies that will allow us to visualize and listen in on the communication between immune cells and other types of cells in human tissue. So we’ll be able to do that for the first time. And that’s really how I’ve always worked: just looking at a part of biology or medicine and noticing that there’s something there that is currently intractable. Then you go to work on building the hammer, which will allow you to reach that nail. 

The approach we’re taking, which is our first set of platforms in development, is referred to as instrumented tissue. So we’re taking engineered tissue models and embedding various types of microfabricated devices that will allow us to either continuously profile biomarkers of inflammation in real time or extract very small samples from the engineered tissue model so that we can do things like proteomics and metabolomics to get a very comprehensive profile of how inflammation evolves over time. These instrumented tissues have quite a technology stack.

IPM: You mentioned “instrumented” tissue. Can you clarify that?

Kelley: We only use this term to refer to the fact that we are introducing scientific instrumentation into tissue. If you think about how labs work, we have all these pieces of instrumentation around the lab; that’s how we take all of our measurements and get all of our data. What if we could have those types of measurement technologies but in a form where they could be interfaced directly with the human body? To me, that sounds like a much better way to keep tabs on what’s going on with your body and the status of your health versus getting a bunch of lab tests once a year. “Instrumentation” just means measuring technology and then bringing it into human tissue and eventually, hopefully, into the body. 

IPM: Do you think people will be amenable to having instrumented tissues?

Kelley: Going back to the CGM, most people are comfortable with that. It’s a patch on the arm. If you’re a diabetic, it has transformed your experience as someone with diabetes. People can really understand that continuous monitoring just has these incredible benefits. And if you’re someone with a different kind of chronic disease, you know about the pain points. If you have heart failure, for example, you live in fear that you’re about to have another episode. There’s nothing that you can carry around in your pocket that tells you how you’re doing.

Anyone dealing with a health problem would appreciate more information, and if it’s just a patch on the arm that appears harmless enough, how far would we want to go beyond that?

It probably means different things to different people. Some people want as much information as they can get about what’s happening in their bodies. Other people just want to let things run their course, and we see technology development or technology adoption at different levels and in different populations of people. But I do think that we’re all starting to understand more than just the impact of prevention. If you look at what’s going on with GLP-1 drugs, we’re seeing that if people have diabetes, weight, and inflammation, there’s a huge potential health benefit. I think we can continue to pile on to that momentum to, again, give people things to help us get at the early signs of disease. 

IPM: How does the funding situation at the CZ uniquely enable your approach and research?

Kelley: I wouldn’t want to write a nice proposal about any of this because there are so many moving parts. There are a lot of unknowns. How do you get metal electrodes to work well with the engineered model of skin? How do you interrogate this model to extract a small amount of liquid? The reviews of these approaches would go on and on in terms of people’s questions, but we can simply take a very ambitious project like this and find the talent we need to take on each component of it, moving quickly. We do not have to sit around for months writing proposals and waiting for feedback.

It’s a way of working that allows us to be very agile and move quickly, and by bringing together these different types of people, we can quickly progress from idea to prototype to something that resembles a piece of instrumentation. That’s a really powerful and unique feature of the model, and it just allows us to take on anything we believe has enough merit and potential impact. 

IPM: How are you focusing your efforts to advance instrumented tissues?

There are three areas where I hope to make a significant impact. As we build this instrumental tissue, we’re gathering data on what’s going on at the proteome and metabolome levels during inflammation. As you can imagine, these are massive data sets and an invaluable resource for those seeking to understand inflammation at the molecular level. And so we’ll undoubtedly use the data sets we collect to identify new modulators of inflammation and things we can target to reduce inflammation in the human body. We’ll also take advantage of the fact that these are large datasets, which we’ll be collecting in order to build very powerful AI models that will allow us to simulate tissue-level inflammation. I believe that simply leveraging what artificial intelligence can do with large data sets will result in a series of discoveries.

Finally, we want things to have an impact in the clinic. By learning how to instrument tissues, we can imagine how we might one day instrument humans and think about the concept of a continuous glucose monitor (CGM), which is a very powerful device in and of itself. A lot of the technology we’re developing could one day provide you with a CGM-like device that tells you about 100 things rather than just one. I’m using that same kind of non-invasive approach. I think that would be incredibly powerful for maybe even not needing precision medicine because we’ll do precision prevention. So, I believe there is a direct link to clinical relevance there. And, again, just discovering the drivers of inflammation is the key to lowering the burden of human disease. Inflammation occurs much earlier. That is when something first goes wrong in the human body. 

IPM: What’s next for instrumented tissues?

Kelley: We are expanding the sensing systems that we’re building beyond inflammation, really trying to go after a lot of the really tricky monitoring applications in chronic disease, and also things like sepsis, which is really hard to manage within the healthcare system. And so we’re building a lot of different systems; we’re also starting to look at how different anti-inflammatory drugs affect different organ-level inflammatory responses, and that’s turning out to be really interesting. So over the next few years, I think you will see a steady stream of papers from us and hopefully technologies that will go on and be commercialized that just really get at what’s happening in real time in living systems. We’re at such an exciting time in this field and the bioelectronics field in particular.

Electronic signals are critical in almost every area of the body, especially the heart and the brain. They don’t work without those signals being highly coordinated. So as we really want to gain a better understanding of how organs work, we’ve got to measure those kinds of things and really understand how they contribute to how the brain works, how cognition works, and how organs break down and stop working. So I agree that there’s been a lot of work there over the years, but I don’t know if we’ve been where we need to be in terms of having the right types of really noninvasive devices to get at the activity kind of in a native setting. That’s why I think this idea of embedding bioelectric materials into a developing organism is just so interesting because it’s just kind of hardwired in from the start. 

I’m not a neuroscientist, but any time I talk to neuroscientists, I get insights into how we think the brain works. But there are still many gaps in our understanding of that. It really is something I marvel at, just the evolution of how that all came together. And also, in thinking about artificial intelligence and where it can go and what intelligence is, and how we got what we have right now, and where we’re going with computation. That’s probably the one that I find most interesting and just amazing. 

I think inflammation is really worth pursuing, but also development, and just the brain at different stages and all of these things. We’re really entering a golden age of being able to measure organism-level biology through devices. That’s incredibly exciting, and so there’ll certainly be more to come from us on that front. 

IPM: What is the implementation plan for instrumented tissues?

So we think about that quite a bit because these tools, they’re not useful unless we get them into the clinic at some point. And that’s not a trivial thing to do—the safety requirements, the accuracy requirements. There’s just a lot of work that has to be done there. This has been the way I’ve run projects throughout my career: you always want to have people in your network who understand the unmet clinical needs and who also understand the barriers to taking things into the clinic. And so with the type of continuous monitoring technology that I’ve described, we understand the use case really well for diabetes. What’s that next use case where you don’t just look at glucose, you look at 10 things, where would that be most informative? You get answers back that relate to just mainly chronic disease management and how problematic it is right now. That’s just a constant work in progress for us: what is the right use case for the technologies that we want to get out there? 

I’ve also spent time with the original founders of DEXCOM to learn more about how that first continuous glucose monitor was developed. What hurdles did they have to get past? So we know what the big practical considerations are and the things where there’s going to have to be a significant amount of work and so we know what we have to do but it’s not trivial, it’s not inexpensive, and there’s a lot of time and money that goes into taking things to the level of sophistication that they need to be for a commercial clinical-grade product. 

IPM: What do you think is the “next big thing” in precision medicine?

Kelley: We’ve done some work in my research group on developing cell-based therapies—incredibly powerful. That’s probably our best hope for curing cancer—truly curing cancer. But we’re not there yet, because the manufacturing aspects are really hard, getting these types of therapies out to people. We’re getting to a place with the ability to do in vivo CRISPR, understanding how to use things like cell therapy.

We have these advanced technologies that are very, very powerful, but now we’re at that scaling problem, and that’s a pretty big undertaking, to go from the small numbers that we can do now to make things really mainstream. There’s also the combination of the two. You can think of using in vivo gene therapy to get cells inside of the body to do the things that you need them to do to eliminate disease or to surveil for disease. So with what we’re learning about the immune system and immunology, we’re just going to have this incredible toolbox to attack diseases that have been intractable. So to me, that’s really, really the future, but there are always these practical challenges that have to be tackled.