Dasha: [00:00:00] Welcome to the Biomedical Frontiers podcast, where we explore pivotal research projects and disruptive innovations aimed at translating scientific advancements into tangible healthcare solutions. I'm your host, Dasha Tyshlek.
Shayn: The micro vessels are part of our body's circulatory system, so, they carry blood, and they carry all of the important things that are contained within blood. Technically speaking, a micro vessel is any blood vessel in your body that is less than 100 microns in diameter. That's about the diameter of one of the hairs on your head, for example. Capillaries are really important, these are the micro vessels we study the most, and in fact every cell needs to be within 100 microns of a capillary or it will not have enough oxygen and nutrients to survive.
They're so critical to human health and function and many diseases cause really bad problems with micro vessels. So, by studying the micro vessels we can try to identify new targets for drugs that we can develop to basically cure and prevent disease. If we look at the leading cause of death in this country according to the CDC 9 out of 10 causes relate back to problems in the microcirculation, you know, heart disease, right? Of course, cancer kind of, hijacks the microcirculation and causes the small capillaries to start feeding tumors. Stroke, chronic lower respiratory disease, Alzheimer's disease and diabetes, these are the two diseases that we study in my lab, profoundly impact and influence the microcirculation.
Dasha: What exactly is that link between Alzheimer's and diabetes that you're seeing?
Shayn: So, we know at the population level 80 percent of patients who have Alzheimer's disease also have diabetes or prediabetes. Additionally, patients with diabetes are 1.5 times more likely to develop Alzheimer's disease. So, the data in the population says, at least suggests, there's a really strong connection between these two diseases.
We make good use of computational modeling to try to help us unravel some of this complexity. Ultimately, I think it's about early detection and early intervention with, you know, drugs and strategies and therapies that can you know prevent the progression of both of these diseases.
Dasha: Welcome back to Biomedical Frontiers. Today's guest is Dr. Shayn Peirce-Cottler. She is the Harrison Distinguished Teaching Professor and Chair of the Biomedical Engineering Department with secondary appointments in the Department of Ophthalmology and the Department of Plastic Surgery at University of Virginia.
Dr. Peirce-Cottler received her bachelor's degree in Biomedical Engineering and Engineering Mechanics from John Hopkins University and her PhD in the Department of Biomedical Engineering at UVA. Dr. Peirce-Cottler develops computational models and combines them with wet lab experiments to study how tissues heal after injury and to develop therapies for inducing tissue regeneration, a popular topic here on this show.
She has published over 125 peer reviewed papers and book chapters and is a fellow in both the American Institute for Medical and Biological Engineering College of Fellows. and the Biomedical Engineering Society. She was awarded the UVA School of Medicine Robert H. Kadner Award for Excellence in Graduate Teaching and Mentoring.
Her courses in Cell and Molecular Physiology and Computational Systems Bioengineering are foundational to the BME undergraduate and graduate studies at UVA. Dr. Peirce-Cottler is passionate about mentoring students and faculty, promoting diversity in STEM and participating in K-12 outreach to increase students interest and self confidence in pursuing STEM careers.
Shayn, welcome to the show.
Shayn: Thank you so much for having me, Dasha.
Dasha: Well, we want to get started with a crash course on microvessels, something that you are an expert in. What are they, what is their function in the body, and what do you research about them?
Shayn: So micro just means extremely small and vessel means a duct or a tube that carries fluid.
So a micro vessel is just an extremely small tube that transports fluid. And what kind of fluid? Well, the micro vessels are part of our body's circulatory system, so they carry blood and they carry all of the important things that are contained within blood, like the oxygen and the nutrients that our cells need to stay alive, the white blood cells, platelets, circulating stem cells, all the cells that need to get transported throughout our body to all of our tissues and organs travel through the microcirculation.
And technically speaking, a micro vessel is any blood vessel in your body that is less than 100 microns in diameter. That's about the diameter of one of the hairs on your [00:05:00] head, for example. So, they're barely visible to the human eye and to see the smallest micro vessels, the capillaries, which are only about five to 10 microns in diameter, we need a microscope.
Capillaries are really important. These are the micro vessels we study the most. They're responsible for delivering, as I said, the oxygen and nutrients to every cell in your body. And in fact, every cell needs to be within 100 microns of a capillary, or it will not have enough oxygen and nutrients to survive. And normally, our microcirculation, these small networks of capillaries are connected to each other and branch structures, kind of like what you see when you look at the back of a leaf and you see the veins running through a leaf. Those patterns are very similar to the patterns of micro, micro vessels in our body.
But if we were to line up all of our capillaries end to end, just the capillaries in our body would actually extend 100,000 kilometers, which is about twice around the circumference of planet Earth. So, needless to say, we've got a lot of micro vessels in our bodies and we are fascinated by them when we study them because they are so pervasive. They're so critical to human health and function and many diseases cause really bad problems with micro vessels. So, by studying the micro vessels, we can try to identify new targets for drugs that we can develop to basically cure and prevent disease.
Dasha: How did you decide to pursue microvasculature as your area of research?
Shayn: So, my story starts back in high school, actually. I fell in love with the cardiovascular system in 11th grade when I was taking AP biology. And I think, you know, it came from the fact that I was a competitive swimmer and I spent like five hours a day in the pool, training and competing.
And I was really fascinated by the connection between my heart, and my blood vessels, and my skeletal muscle, and how it could be that, you know, my heart could pump blood throughout my body and deliver enough oxygen so that my muscles could help me swim down the pool. At the same time, my dad was an engineer and he's actually engineering professor at Duke.
He's one of my heroes and my mentors, and he introduced me to engineering, as a discipline where I could, you know, find more of the things that I love. So, even as an 11th grader, I knew I liked problem solving. I liked helping others, I'd like to be creative and designing things and teamwork, and I was really curious about studying the microcirculation and the small blood vessels.
And, I thought, you know, being a biomedical engineer would be a great way to do that. so I went to college and said, I went to Johns Hopkins. I pursued a major and undergraduate major and BME, and I swam there for four years on their swim team. And, I was lucky enough to do undergraduate research, in the laboratory of my mentor, Bill Hunter, and I also was able to take this amazing class with Dr. Sasha Popel called Physiological Fluid Mechanics. And those two mentors were really the first to, you know, expose me to research, and expose me to how we study the microcirculation and blood vessels in the body, and they pointed me to UVA where I came for a graduate school and earn my Ph. D. with Dr. Tom Skalak, who I think is a previous guest on your show.
And it was there in the lab, as a graduate student, that I got to see my first micro vessel and it was just a transformative experience looking under the microscope and seeing this beautiful small capillary delivering, these incredibly, organized, red blood cells and white blood cells, you know, throughout this network of tissue. And so I just fell in love with it and I had about a million questions. And so I just wanted to start studying it, and honestly, that's what I've been doing for the past 25 years or more, just looking at small blood vessels and trying to figure out, you know, what they do, how they grow, and how disease affects them.
Dasha: Is there something that you have learned about microvessels, in all of this extensive study, that you wish that everybody would know so that they would have better health?
Shayn: Yeah. So, we already talked about the fact that these microvessels are crazy abundant in your body, so it's only natural that so much of our health and our propensity for disease would be determined by the health of our microvessels.
In fact, some people refer to the microcirculation as a systemic organ, which reflects the fact that micro vessels are, you know, within each and every tissue and they're actively regulating our health and serving as a common target of disease. So, if we look at the leading cause of death in this country, according to the CDC, 9 out of 10 causes relate back to problems in the microcirculation.
So, for [00:10:00] example, you know, heart disease, right? Like, that is a critical source of problems that start in the microcirculation, that lead to heart disease. Of course, cancer, kind of hijacks the microcirculation and causes the small capillaries to start feeding tumors. You know, COVID was a major cause of death, and the reason why we get infected with the covid virus, the SARS virus, is because the receptors on that virus bind to endothelial cells in our small blood vessels.
Stroke, chronic, lower respiratory disease, Alzheimer's disease and diabetes, these are the two diseases that we study in my lab, profoundly impact and influence the microcirculation. So these small blood vessels, they're everywhere and they are incredibly important to your health, and to disease, and they do a lot more actually than just deliver, you know, blood and oxygen to your tissues. They also deliver stem cells, so when you need to regenerate, you better have a healthy microcirculation so that your stem cells can get to where they need to be in order to regenerate a tissue.
Dasha: What is kind of the frontier of knowledge for micro vessels right now? What is it that we don't know about them at all, but need to?
Shayn: So, I love talking about frontiers, but also before we get to that part, if it's okay, I'd like to kind of honor the past, because it's sort of a fascinating story about how we even discovered microcirculation.
So it turns out that back in the 1600s, there was an anatomy professor, Marcello Malpighi, at the University of Pisa, and he was the one who, because of the fact the microscope had just been invented, was able to visualize the microcirculation in frog lungs for the first time. And, I think this is just a great example of how technology is, you know, what enabled this new scientific discovery, the existence of the microscope, is how we saw the first micro vessel.
And of course, you know, even before then about 30 years earlier, William Harvey, who was a famous English physician, and he was the physician to King James, the first and King Charles, the first, and he published this incredibly important book called De Motu Cordis, which means on the motion of the heart. And he basically postulated that there had to be capillaries that connected the arterial tree to the venous tree in the body. So those foundational discoveries kind of set the stage for appreciating the importance and the abundance of these small vessels in our body.
So now to the frontiers, you know, where are we headed? Well, I think one of the most amazing things about the microcirculation is that we're appreciating that it is not a stagnant set of networks of blood vessels. These blood vessels are constantly changing in our body in ways that we don't completely understand, but I keep saying it over and over, definitely contributes to disease.
And so I think, kind of where the field is headed is understanding the interactions between the cells that comprise our blood vessels, the endothelial cells, which line all of our blood vessels and the pericytes, which wrap around them. Understanding how those two cells communicate with the rest of the cells in our body and respond to changes in our environment, over the duration of the human lifespan.
So, understanding those dynamic processes, so these micro vessels are growing, they're regressing, they're morphing, they're changing shape, they're connecting, and uncoupling, that's happening all the time in our bodies. A great example is when we go to the gym and we start to, you know, work out and we build some muscle.
Of course, our muscle grows, but guess what also grows? Our microcirculation is expanding and growing so that it can feed the new muscle tissue with more oxygen and nutrients because it has a higher metabolic demand. So understanding the communication of these cells, how they're responding to their environment, how they're dynamically changing, and how these changes happen in different organs differently.
So, we now know that the capillaries in your brain are really quite different from the capillaries in your heart, and the capillaries in your lung, and your liver, and your bicep. So, it's important to understand those specific differences and how they influence cell behaviors that would contribute to disease.
Dasha: Sounds like a really exciting and promising area of research and one that could have so much benefit to human health. You just published a paper Brain Microvascular Parasite Pathology, which is a mouthful but we're going to get into what that means, Linking Alzheimer's Disease to Diabetes dot Microcirculation.
And I think for many people, this idea, okay, there's a link between [00:15:00] Alzheimer's and diabetes. This might be huge. These are two very difficult diseases, ones that are very prolific, very devastating to people's lives. So, let's dive into this. What exactly is that link between Alzheimer's and diabetes that you're seeing?
Shayn: So, we know at the population level, 80 percent of patients who have Alzheimer's Disease also have diabetes or prediabetes. Additionally, patients with diabetes are 1.5 times more likely to develop Alzheimer's disease. So, the data in the population at least suggests, there's a really strong connection between these two diseases.
And in fact, you may have heard, you know, in recent terminology, people are saying Alzheimer's disease is essentially a type 3 diabetes. So, we know there's a link between these two diseases, but we really don't understand what that link is is and our hypothesis is that this link is one of the important links, connections link between Alzheimer's and diabetes, is happening in the microcirculation.
So, I mentioned this before, there's two types of cells that comprise our microcirculation, the endothelial cells, these are the cells that line all of the blood vessels in our body from the biggest blood vessel, the aorta that connects to our heart down to the very smallest capillary, and then the pericytes, which are cells that wrap around or encase the endothelial cells, kind of like, you know, a loose insulation around a hollow tube.
So it's really critical, not just in the brain, but in all of our tissues and organs that the relationship, the connection, between the endothelial cells and the pericytes is very healthy and robust and tight and strong because the pericytes are instructing the endothelial cells about what's going on and the endothelial cells are instructing the capillaries.
And regulating things like permeability of capillaries, so fluid leaks from capillaries into tissues, that's a normal healthy thing. And, the rate at which that happens is regulated by pericyte-endothelial interconnections. The amount of blood that goes through capillaries, especially in the brain, can be regulated by the extent to which the pericytes are wrapping around and physically constricting the capillaries. So, actually, blood flow in your brain is regulated by the connections between endothelial cells and pericytes. So, it's really important that these connections are stable and our hypothesis is that in both Alzheimer's and diabetes, these connections between the two cells are falling apart.
The relationship is breaking up. These cells are no longer communicating and that's causing excessive leakiness of blood vessels. So, the fluid that normally flows out, more of it is flowing out in the brain than should, it's causing additional inflammation and also changes in blood flow that could be really harmful for the neurons that are relying on oxygen and nutrients that these micro vessels are delivering.
Dasha: So, can you go into a little bit of what that actually looks like when you're studying this relationship? How are you able to study the relationship between these two cells at such a molecular level? And how are you able to detect that it's being disrupted in some way and correlate the differences and similarities between how it's disrupted in these two diseases?
Shayn: Yeah, so, in order to study blood vessels is really helpful to study them in, you know, a living organism, ideally a mammal where there is a heart and a fully developed microcirculation. So, a lot of our work is done using mouse models, and there are a number of different mouse models of disease, both diabetes and Alzheimer's and so we have mice that have diabetes.
We have mice that Alzheimer's and we have mice actually now, that have, you know, combinations of both. And so in those mice, and this is all work that's done in very close collaboration with Eyo Ukpong, who is a professor in neuroscience at UVA. In these mice, we can install cranial windows, which lets us peer into the brains using microscopes to see literally see what's going on between the connections, between the endothelial cells and the pericytes in the brain.
So the amazing thing, and I have the incredibly talented PhD student, Kareem Al Ghazali, working on this project in my lab right now. Kareem's done some beautiful work tracking individual pericytes and endothelial cells over days and weeks as these diseases manifest in the brain and watching these cells kind of start out, you know, happy and healthy and snuggled up against one another. And then over time, as [00:20:00] the diseases progress, as I said, this relationship kind of breaks down, and then, as a result, we're seeing changes in the physiology of the brain, seeing unusual things that shouldn't, you know, be happening, that wouldn't be happening, if those diseases weren't present.
So, a lot of it is the same way, Dr. Malpighi, back in the 1600s, was making observations of the capillaries. It's just taking capillaries and looking at them under the microscope over time and watching these incredible dynamic of events.
Now, in addition to this, these things are complicated. These relationships, as you mentioned, the molecular signals that control this relationship, you know, they're complicated. You know, there's hundreds of molecules that contribute. And so, we make good use of computational modeling to try to help us unravel some of this complexity.
So, as we are also making these observations in the lab, on the bench, we're developing computational models to try to understand how endothelial cells and pericytes communicate and how these diseases might disrupt the molecular signals that are orchestrating that communication. And, so it's really by combining the computational modeling with the experiments, that we think we can move the needle and try to understand some of these complicated mechanisms and how they change over time.
Dasha: And in terms of root causes, so you're seeing a specific effect that's present in both diseases. Is it providing any clues as to the potential root causes of either or both of the diseases at a kind of bigger scale?
Shayn: Yeah, so that's an awesome question. And that's a really hard question to answer because there's so many potential root causes.
So, you know, one is that, hypotheses that are out there is that, diabetes, obviously, you have the levels of hyperglycemia, high levels of blood glucose, of sugar in the blood, essentially, and those high levels of sugar can affect the glycation of basically, you know, proteins and carbohydrates, that bind to the endothelial cells. And, we think that could be a possible reason why the pericytes are getting signaled that those endothelial cells are sort of sick as they're sort of collecting these sugars on their surface.
That's one hypothesis that we're pursuing. There's also suggestions of inflammation being a driver or connector of both diseases that kind of intersects the level of the microcirculation. As I mentioned, every, white blood cell, every inflammatory cell has to travel through a capillary to get to a site of injury or to get into a tissue, including in the brain.
And so there's a lot of crosstalk between inflammatory cells and blood vessels, and we think that that could also be a driving reason why in both diseases the connection between endothelial cells and pericytes is getting, you know, disrupted and kind of going off the rails. So a lot of questions and we're trying to dig into it, and see where the science takes us.
And ultimately, you know, if we can understand these mechanisms, the ideas to develop new therapies that would ameliorate and kind of get things back on track.
Dasha: How do you think some of this research, and understanding that there's a long way before this gets translated to treatments, but how do you think this type of research could actually impact the treatment of Alzheimer's and diabetes?
Shayn: So, ultimately, I think it's about early detection and early intervention with, you know, drugs and strategies and therapies, that can, you know, prevent the progression of both of these diseases. So, obviously, these diseases develop, you know, over a lifetime. They're very long term. They're, you know, kind of diseases of aging, they're associated with aging. And so, I think recognizing the early symptoms, the early signs and having tools where we can go in and intervene, is going to, you know, obviously make the biggest impact, especially for our aging population.
Dasha: Are we actually, this might sound like a dumb question, but are we able to take tissue samples in a human and actually see some of these effects that you're describing seeing in mice, but maybe without the brain window?
Shayn: Yes, no, it's not a dumb question. No such thing as a dumb question, it's a great question. So, it's hard, like, we can't put windows in human brains and we can't take samples of brain tissue very easily.
But one of the levers that we have is the fact that our eyes, actually, our retinas are a window into the brain. So, your eyes are part of your central nervous system, and so it's neural tissue there, and the great thing about our eyes is that they're, you know, [00:25:00] optically pretty clear, and we can look into them.
In fact, you know, our annual eye exam and our ophthalmologist takes pictures of the back of our eyes. And guess what? There's a lot of blood vessels in our retinas. And those blood vessels we think are behaving in very similar ways to the blood vessels in our brain. So by peering into the eye and looking at the blood vessels that live there and micro vessels, the capillaries there, we think we can actually kind of see, in a much more, you know, accessible way what might also be happening in the brain at the same time.
So we're now collaborating with ophthalmologists and other experts who do a lot of imaging of the eye, to try to correlate the findings that we're having in the brain with those that we've also observed in the retina, in the diabetes conditions.
Dasha: That's incredible. Well, at the beginning of this topic, you mentioned that, there are many people thinking about this connection between diabetes and Alzheimer's.
You're focusing on the micro vessels. Are there other areas of research into this in other areas of the body that you are finding really promising and interesting?
Shayn: Yeah, so, you know, I mentioned, inflammation being a common connector and our collaborator, Dr. Eyo and the neuroscience department has some beautiful work where he's studying how the microglia, which are basically sort of the macrophages, or some of the, you know, immune cells that live in our brain all the time, how they are changing in to these diseases and also their intersection and communication with the blood vessels.
So I'm really excited to see that work develop. Also there's, you know, hypotheses about mitochondrial dysfunction and metabolism. You know, we're talking about blood flow here and oxygenation, so of course your cells and their metabolism are going to be very tightly controlled by how much oxygen they're getting.
And so I think there's a lot of interesting changes that are happening in both diseases at the level of the mitochondria, carbohydrate metabolism, I already talked a little bit about, insulin resistance being a key driver of amyloidosis, which is this notion we've heard about it in Alzheimer's where you get these amyloid beta plaques developing.
And there are suggestions now that changes in our pancreas and response to diabetes can actually get communicated up into our brain and further contribute to plaque development. So, there's all kinds of fascinating research that's coming out now. And I think biomedical engineers have a really important role, because we're systems thinkers, and we are great at connecting different organ systems, different concepts, different ideas and complex ideas and figuring out where the key drivers are.
Dasha: Well, this has been a really fascinating topic, but I want to switch gears to another one that you're so deeply expert in and it's a topic we've already started to dive in a little bit on this podcast, actually, with two different episodes. Episode with Dr. Jennifer West and with Dr. Griffin and Dr, Daniero, which is specifically about, synthetic tissue, tissue regeneration, and regenerative medicine, and also, within that, specifically blood flow, which seems like a really big challenge to overcome.
Your own work also focuses on this challenge, which shows just how important it is that there's so many people trying to work it out and figure it out for different tissues. Can you give us an overview of the work your team does on regenerative medicine and also how that connects with things like synthetic biology and other terms that we have heard on the show?
Shayn: Sure, so, yeah, I really enjoyed listening to Dr. West's podcast. I think she explained it beautifully, this notion that a tissue is not going to heal, it's not going to regenerate without a vascular supply providing oxygen and nutrients.
And so it's really a bottleneck, honestly, getting these small vessels to grow into a tissue that's trying to regenerate, or if you're going to say bioprint or biomanufacture a tissue that you're going to then implant into the body, if it doesn't have a circulation, if it doesn't have a way to get those blood cells there it's just not going to survive, or it's not going to survive for very long. So, it is a critical bottleneck and it is something that that we're working on. It's challenging, as you said, because, you know, cells are alive, right? We kind of take that for granted. But what does that mean?
It means as engineers, as much as we're trying to control things, we actually have very little control over what our cells do. When we print them into a tissue engineered construct, or when we inject them into an injury site and, you know, provide a biomaterial to support them, there's a little bit of just kind of [00:30:00] crossing our fingers and hoping that they do what they're supposed to do, which is form blood vessels and, you know, get the tubes formed so the blood can flow through and deliver the oxygen.
So, you know, we hope we hope it works and we're trying to figure out the conditions. You know, what are the biomaterials? What are the, extracellular matrix queues? What are the mechanical queues that blood vessels, you know, need to see in order to do their thing, which is grow into this regenerating tissue.
And so our angle, how I think we complement a lot of the work, in the Griffin lab and in the West lab, who we collaborate with a lot, by the way. Our angle is to bring in the computational modeling and kind of appreciating that you know, as I said, I keep saying it over and over. These systems are complex. There's a lot of molecules, a lot of cell behaviors, a lot of cues, not just chemical, but mechanical electrical. And how do we bring that together? Well, we use computational models to simulate these processes.
And the great thing about models is that they're kind of playgrounds, to put in what we know and say, do we know everything we need to know in order to predict whether this, microvascular network is going to form in this by material. And sometimes we have pretty close, a model that comes pretty close to what we actually see in the experiment. And we say, okay, we probably know most of what we need to know. But a lot of times our models fall short. And they don't do a good job at predicting what we're seeing in the experiments with these cells and biomaterials.
And that's actually even more helpful. I think, because it says we need to go out there and do some more experiments and get some more data. And often it points us in the right direction of where to start looking. So, by bringing in computational models, it kind of helps us grapple with this complexity. And it helps us know what to look for and what we're missing.
Dasha: You've mentioned computational modeling is such an important part of your research and your lab. What are some specific approaches that you guys have used in your modeling in order to think about blood supply in growing tissues?
Shayn: So, our bread and butter when it comes to modeling, is agent-based modeling and it's a type of modeling that's been used actually for decades by epidemiologists and ecologists. It's a way to study emergent phenomena in a population of individuals. So, a lot of the modeling of COVID, for example, was done using agent-based models, trying to understand the spread of COVID where we're simulating individuals in Charlottesville, for example, and they have interactions with each other and they have exhibit individual behaviors.
They go to the grocery store, they wear a mask, they wash their hands, they go to school, they get sick. They stay home for two weeks. What are the consequences of those individual behaviors at the population level? How does COVID spread throughout Charlottesville when the individuals are each kind of doing their own thing?
So, agent-based models are perfect for studying those sorts of questions. And we recognized back in graduate school, that they can also be useful modeling approaches for studying how cells interact and what are the consequences of individual cells in the tissue, interacting and changing over time.
So, we've been developing agent-based models to study, capillary growth and remodeling and regression for a very long time. And kind of the new frontier, which is the no surprise is that, you know, AI and machine learning are now here, and they're robust tools for amplifying the power of mechanistic models like agent-based models. So we can do, you know, massively high throughput simulations that we weren't capable of doing previously and understanding patterns in the predictions of those simulations.
So basically, by bringing together artificial intelligence machine learning tools, we can make even more out of these incredibly complicated agent-based models to try to understand how cells interact and how those interactions over time will produce a emergent phenomena like a tumor recruiting a new vascular network or a biomaterial effectively recruiting a new capillary network into a regenerating tissue.
Dasha: For people who are not as familiar with agent-based modeling applications, particularly in biomedical and bioengineering, work, could we go into maybe an example of something that you've done in your lab that shows some of the best practices and also ideas that your team has developed about how to, you know, apply this tool to biological problems effectively?[00:35:00]
Shayn: Yeah, so, as I mentioned, you know, when we started, doing agent-based modeling, it's actually back when I was in graduate school, there weren't too many people applying this type of modeling approach to biological tissues and to study multi cell behaviors. And so, we kind of had to figure it out along the way, and, we started collaborating really closely with a lot of amazing researchers here at UVA. Silvia Blemker is one example, Jeff Saucerman, Jason Papin, Kevin James, a lot of my colleagues here. And you know, through those interactions, what came out of it is, kind of, deploying best practices in computational systems biology, to agent-based modeling.
So, there are other types of modeling, the finite element modeling that Silvia does in her lab, for example, that has been used for many more decades than agent-based models to study biological tissue. And there are some really important practices. How do you build a model? How do you validate a model?
How do you find parameters appropriately that describe the biology and put them into your model, so that your model predicts something that could be, you know, relevant to what you're studying? Borrowing tools, from other modeling approaches, I think has been something, that has been really important and really enabled by the incredible community we have here in biomedical engineering, in terms of the researchers that study and use computational systems models to study complicated biology.
Dasha: Where do you see a potential future applications of agent-based modeling that, maybe even outside of of biomedical engineering or within it, where you see, there could be real good potential for exploring this tool.
Shayn: So, what we appreciate in biology, known this for a long time, but it's really been a challenge to study is that there are cause and effect mechanisms across spatial and temporal scales.
So, what does that mean? Well, it means you have changes in gene expression inside a nucleus, which then will cause changes in protein in the cytoplasm cell which then will cause changes in the immediate surroundings outside of that cell, which then causes changes in other cells, which then causes the tissue to change, which causes the organ to change.
So there are cause and effect, mechanisms happening across, you know, very small, microns, even smaller, up to meters, if we're talking about the human body. And so, wrestling with this, you know, things are changing across scales is something that has always been a challenge and the field of computational systems biology has introduced tools that enable multi scale modeling. That's actually what we call it, multi scale modeling. And, it turns out that agent-based models, because they can model individuals in a population, are really great kind of starting place to build multiscale models. So, one example is we're collaborating with Jeff Saucerman here at UVA to do a much more refined simulation of the intracellular networks, the signaling networks inside of cells that drive cell behaviors.
So, we're now modeling inside the cell at a very small scale, and we're able to, thanks to the agent-based models, model outside the cell and tissue level as well. So it's kind of, bringing together the biology across all of these spatial scales from nanometers and hopefully up to, one day, up to, up to meters, where we have a simulation of the entire body, representing every single cell.
It will happen one day. I'm not sure in my lifetime, but it'll definitely happen one day. And then, when you have that I mean, just think about the potential. We're talking about literally a digital twin, right? Like, we could have, you know, the Dasha and then we could have the computational Dasha that has every cell in your body represented as, you know, as a unique entity as it is, but interacting with its neighbors and, you know, driving health.
So that's ultimately where things are headed and I think that's where agent-based modeling can play a unique role is it's the level where the cells interact, that's what we're simulating. And, we can scale up and we can scale down very easily by coupling agent-based models with other modeling approaches like the ones that are being developed in the Saucerman lab.
Dasha: So, that is very interesting because when we've talked about multi scale modeling on this show, what we really talked about is that the same lab is doing modeling at multiple scales, but in separate experiments and in separate models. So, here you're modeling the cell level and then here you're doing the tissue level and then separate of all of that, you're doing the human body level and it takes [00:40:00] human interaction to bring the ideas from one to the other.
What I heard you describe is that using the agent-based modeling we're able to scale the model to include multiple levels simultaneously, like the cell model into the full tissue and you're able to see the impact of one translate into the model of the other. Is that a correct interpretation?
Shayn: Exactly. Exactly. You need to come and come back to UVA work in my lab, Dasha. You totally get it.
Dasha: I've been thinking about it. I've been really thinking about it. Well, going forward with computational modeling, AI digital twin concept, what is it that needs to change or evolve in our education in order to prepare students to be able to take on problems through modeling?
Shayn: So, this answer might surprise you, but I am convinced that students are entering our programs are graduating from high school with more computational skills and acumen than ever before. I had two amazing high school students in my lab this summer. They knew a ton more about AI than I did, their coding proficiency was on par with that of, you know, fourth year undergraduate students.
And, I think that the challenge from the educator standpoint is to keep up with these amazing young people who are entering the field of biomedical engineering, completely equipped to do unbelievable things. So, yeah, I think the future of computational modeling education is to kind of harness that power. The appetite that these students have for coding and the curiosity they have for trying to understand biology and ultimately, you know, come up with cures and medicines that leverages that knowledge and the and their coding skills, I think that's all there.
I think what we need to do is maybe do do a better job, kind of, helping students frame the questions, right, because it's easy to get lost in the forest these days. There's just so much out there, so, really emphasizing how do you take all those skills, all those questions and put them into a framework where you can go from A to B to C and answer a question, and the higher level thought processes, the strategies, you know, how do you deploy these things so we can get an answer? So it's no longer teaching the skills because the students come in with the skills. It's teaching them what to do with it, with their skills to, to understand these complicated problems.
Dasha: And I also know, you guys are working on a new curriculum and some new programs within the BME department. What are they and how are those going to affect the student experience?
Shayn: Yeah, so for as long as I've been in our BME department, which is over 27 years now, when I first joined as a grad student, our department's teaching mission has been to provide the highest quality educational experience possible. And, we've received national recognition, you know, over the years for doing that.
What's new now is that we're expanding our educational mission to ensure that every single student in our program, regardless of background, however you defined it, you know, where they're from, the high school they attended, the access they had to AP courses, socioeconomic background, sex, gender identity, race, ethnicity. Whatever makes them unique, every single person who comes to UVA and wants to be a biomedical engineer will be supported by our faculty and throughout our curriculum and our courses to learn the skills necessary to be a high achieving biomedical engineer.
So we're really talking about accessibility and providing our students with a sense of belonging. So, from day one, they know no matter what their experiences prior to coming to UVA, they have every potential to be one of the best biomedical engineers in the world. So, how are we doing this?
Well, we're increasing our accessibility to students, we're opening up courses, making courses available that were previously limited, creating new courses. We have a brand new course coming online this spring. It's a course in engineering for women's health. That's going to be taught by Dr. Shannon Barker.
We're elevating our support that we're providing to our students, by teaching the teachers what it means to be a supportive mentor, to students from diverse populations. Appreciating the diversity in each one of us, and then we're really revamping our advising and our mentoring with a focus on career planning from day one.
So, when students come to you, they are already on track to start exploring what are their unique strengths and what industries, what higher education, what avenues are out there for them in the future where they can leverage their unique strengths to be truly a contributor and someone who's making a real difference.
And, we're doing that, actually, by connecting [00:45:00] students with alumni in a much more intentional way where students can have conversations with alums and talk about life experiences and shared career goals and kind of plot out a path, and see what the possibilities are so they can start looking for them, and planning for their futures.
Dasha: And I know one of the big changes also has been the size of the BME engineering class, used to be, there was a limit to the number of people, but, and that led to many people who wanted to be biomedical engineers, if they didn't get into the program because their first semester, their first year, they maybe struggled in a class, or they were still adjusting.
But now you guys have opened it up. You are not limiting the number of BME's. What has been the impact of that on the school school in general. And where do you see that heading in the future?
Shayn: So, yes, as you said, one of the best things our department did was get rid of the cap. We called it a cap, which you said basically was an enrollment cap based on GPA in your first year.
And, you know, we all know that GPA in your first year is not a very good predictive of your potential to be an amazing biomedical engineer. So, as soon as we did that, instantly, our, our class size got larger because biomedical engineering is popular. A lot of people want to do biomedical engineering.
Our class size got more diverse. Our class quality went up dramatically because we had more diverse students working in diverse teams, coming up with more creative thoughts that had more impact on more diverse populations. So, it had an immediate impact on the student body and what they were able to accomplish and that reflected back on our school and on our department. You know, the things we're doing now as a result of, you know, having those talented students, diverse students, more students in the program, I think has made us, you know, truly different than we were back when we had that cap.
So, I think one of the best thing that's happened in our department since, since I got here, actually.
Dasha: Well, I think it's also encouraging to hear kind of from a global perspective, because, when I read reports on industry growth challenges and an industry across all stem, disciplines, there is a shortage, an anticipated greater shortage of skilled employees in the coming decades and for specifically biomedicine as a really growing and expanding area, still very much an emerging field, that's really taking off. There is an even greater challenge there than some other disciplines in terms of the number of people being graduated with the skills, and, you know, my observation for biomedical engineering, you oftentimes need advanced degrees in order to really be able to work on some of these really advanced problems.
It takes that much expertise and experience and mentorship to get to a point of independently problem solving in such a complex area. And so, to get to having that many graduate students, you got to have a lot of undergraduate students at first because not obviously not everybody's going to go to graduate school and do that.
So, I think from an industry perspective, this is also so encouraging to hear this should encourage the alums and industry professionals who are listening to the show to get involved in the program for mentoring students.
So we're calling alums and biomedical professionals who are interested in mentoring to reach out to Dr. Shannon Barker, director of the undergraduate program in the biomedical engineering department at UVA. And the project is called project connect. So if you reach out to her, say project connect, we'll post a link, about this. So that anybody who's interested can become a mentor and with a larger class size, we need more mentors.
Shayn: Absolutely. Thank you, Dasha. That is exactly what we need and where we're headed. There's so much potential in just a single conversation between an alum and a student, to open doors, open ideas for that student, open new pathways, show them possibilities of, you know, where they can go.
You mentioned biomedical engineers are well equipped to do so many important things in society. And our training is inherently broad, but also deep. And, I think that's a unique type of engineering training. In that role, with that training, we are the connectors, we're the communicators, we can bring together other engineers and doctors and patients. And, with problem solving skills and the analytics skills that we provide our students really the sky's the limit.
There's so many places our graduates can have an impact and to help them find those places where they can really shine, and, you know, do a job that brings them joy and really helps other people. They need exposure to what's out there, and the way to get that exposure is is through [00:50:00] the mentoring that can be provided by the people that are out there by the alum.
So, I thank you for making that call to action. It's absolutely critical for our students to reach their full potential. And we greatly appreciate appreciate people who are interested in participating in BME project connect.
Dasha: Well, Dr. Shayn Peirce-Cottler, it was such a pleasure having you on the show. We learned so much about our body and new models, new methods for computational modeling.
Hope you enjoyed the show and thank you for joining us on Biomedical Frontiers, Stories with Innovators in Healthcare.
Shayn: Thank you, Dasha.
David: Thank you for listening to Biomedical Frontiers, stories with innovators in healthcare. My name is David Chen and I am the Managing Director of the Wallace H. Coulter Center for Translational Research at the University of Virginia. Our mission is to help bring promising new biomedical research and technology into the hands of the provider and the patient.
If you found this episode valuable, please let us know by subscribing, following, or sharing. You can learn more about our promising translational research projects on our website. See links in the show notes.