CCTS KL2 scholar, Dr. David Tofovic, talks about his work at the intersection of heart health and sickle cell disease.
David Tofovic, MD
Assistant Professor of Clinical Medicine
Department of Medicine, Division of Cardiology
UIC College of Medicine
Find Dr. Tofovic on X @tofovic
If you would like to see your interdisciplinary team featured on the podcast, reach out to me at laurenw@uic.edu.
0:00 Dr. David Tofovic:
We have to be very careful when studying in large scales like this. We’re basically looking at numbers and some outcomes. And those outcomes are basically a 0 and a 1. And there's people that that represents underneath.
0:10 Voice Over (VO):
Welcome to Collaborative Endeavors, a podcast about how experts from different areas of research come together to tackle big health challenges, leading to better therapies and healthier communities.
In this episode, we meet one of CCTS’s newest KL2 awardees in the Clinical and Translational Scholars- or CATS- program. Dr. David Tofovic is an assistant professor in the division of cardiology, assistant program director for the cardiovascular disease fellowship, and the director of education for the Center for Cardiovascular Research, as well as medical director for the heart center and cardiac ambulatory services. On top of his many clinical hats, he is also principal investigator for the UIC Sickle Cell Disease Cardiovascular Database (S(CD)2) and the UIC Multi-Ethnic Dilated Cardiomyopathy (DCM) Registry. The latter is currently funded, in part, by a CCTS pilot grant award.
Fortunately, Dr. Tofovic found time to speak with me about his work on atrial fibrillation in sickle cell disease, which underpins his KL2 mentored career development award. We started the conversation with his professional background and what led to him to the intersection of heart health and sickle cell disease.
01:30 Tofovic:
If I had to ask myself where I saw myself in ten years, I would have said this, but then how I got here is very different than I would have assumed I would get here. There's always that picture of a straight line to success, and that's never it. There's always these little roadblocks, and you learn these different tools and try these different experiments and things like that. My background is really in a study of rare diseases and the junction of hematology and cardiovascular physiology. I did my training for fellowship here at the University of Illinois Chicago, where I did a cardiovascular disease fellowship, and a general cardiology fellowship. Before that I was at Case Western Reserve University. I did, I think, a whirlwind tour of kind of deep diving into clinical and translational research. I started in bench and translational research in college, then went to med school, focused on med school, continued some bench and translational work. And then in residency, really got the translational clinical bug and when I was done with residency and applying for cardiology, I knew that I wanted to do a research fellowship and I knew that I wanted to study, in particular, sickle cell disease and the cardiovascular effects of sickle cell disease. Which is what brought me here to UIC, which, you know, we're a sickle cell disease center of excellence, and there's a great team of hematologists and multidisciplinary team there.
2:40 VO:
For those who may not be familiar with sickle cell disease, it is a genetically inherited disease where the body produces red blood cells shaped like crescents or sickles. These don’t live as long as typical red blood cells, which leads to anemia- a low red blood cell count. The sickle shape also causes the cells to get stuck in blood vessels, blocking blood flow. Beyond anemia, symptoms include repeated infections and periodic episodes of pain. While the National Institutes of Health categorize sickle cell as a rare disease, Dr. Tofovic explained that this is far from an accurate depiction of the condition.
03:20 Dr. Gaber
I think rare diseases as a concept is a bit of a misnomer, and that's some of what I've devoted my life to. If you look at the continental United States, you're talking about probably 300 to 350,000 individuals with sickle cell disease, likely somewhere between 25 to 35 million across the world. That's not a small number of human beings that that are born with and live with sickle cell disease. The landscape in sickle cell disease is much more heterogeneous or varied. You know, different people get different treatments. Different people have different opportunities to care. Different people tolerate treatments differently. And so, there's this wide range and wide spectrum of how that disease, even without treatment, presents in people, and how it affects their lives. But also, when some people get treatment or can tolerate it and others can't, it kind of creates this big disparity in how we're treating that disease and how well we're doing at controlling the symptoms and the effects of that disease. For a long time, you know, we ignored things like this in in rare diseases, sickle cell disease being a great example. These are people who have a lifelong condition, who have very frequent hospital use for many of them, and it's a debilitating condition for a lot of people. And there's others who are able to live more able lives who are not as affected by the disease, but it still affects everyone who has it. I think the scientific community is finally starting to recognize that.
Classically, what we've thought of about diseases like this, and about sickle cell disease as a whole, is just not sufficient in how we study it. I think for a very long time it was considered a blood disorder, and it just affects the blood, and maybe it'll affect one organ or two organs. And I think of myself and some of the work that I've done, and others have done, and we've shown that it's a whole body illness, and it affects multiple organs. I mean, for a long time you thought it didn't do anything to the heart. Well, no, that's not true. We thought, you know, the kidneys take hits. Yes, they do. But there's also neurologic [DT1]disorders, liver disorders, pain disorder. There’s a lot that happens in this disease that hasn't really been touched on. On top of that, with some of those aforementioned treatments that I mentioned, people with sickle cell disease are now living longer. But what's really unfulfilling to myself, and as somebody who cares for individuals with sickle cell disease, is that we've really plateaued in how long people are living who have sickle cell disease. And there's this huge gap still in between those individuals and the general public that doesn't have it. That doesn't carry both genes for sickle cell disease. And so, there's a lot of work to be done.
For myself, the heart is my bread and butter. It's what I do for a living. What we're starting to see now is these two factors coming into play here. One is that sickle cell disease itself affects heart, and there's some unique changes that happen to it then. You see that now, luckily, a lot of people with sickle cell disease are living older than they were before, they're living much longer. Still, there's a gap compared to the general population, but they're living much longer. And so, we're starting to see things that happen to the general population start to creep into sickle cell disease. And then there's the interplay of those two things. And people haven't really started to study that and take a look at when you have a disease that's rare, like sickle cell disease. Sickle cell disease is challenging to study for a couple of reasons. You need a big enough sample size, or you need a big enough group of people to be able to study something well enough. And sickle cell disease, for a long time, we just haven't had that. The studies that you look at in sickle cell disease, the kind of landmark ones, are still relatively few people. I mean, when you look at a heart disease trial, you're talking, you know, 5, 10 hundreds of thousands in some case, and we just don't have that here. But what's exciting for us is that we're in this kind of new dawn and bustling age of technology that allows us to interconnect systems and process these larger bundles and larger groups of data. Now, what we're looking to do with my project in particular, is we're focusing our cohort here at UIC, and then we're going to hopefully expand this in the future to a couple of multi-site groups to see if we can really build a robust data usage for everybody.
07:17 VO:
Dr. Tofovic described his interdisciplinary mentor team and how their respective expertise helps to fill gaps in his professional training.
07:28 Dr. Tofovic:
As a whole, there's not a lot of heart doctors that look at sickle cell disease. I think that there's only a handful of us in the entire world that are doing it. I've been very fortunate because the sickle cell disease community is still smaller, particularly in the continental United States. Right now, I'm focusing particularly on arrhythmias or abnormal heart rhythms and sickle cell disease. But I've had the wonderful opportunity to partner with and really get trained by some of the “who's who” of people in this. So, my primary mentor, Dr. Darbar, who is a world renowned expert in atrial fibrillation and the genetics behind atrial fibrillation, the physiology behind atrial fibrillation. And Dr. Santosh Saraf, who is a very well respected expert in the kidney effects of sickle cell disease and sickle cell disease as a whole. So UIC was just this little hub for me to kind of come in and really just be able to interact- let alone get mentored by- some phenomenal human beings who are really pioneers in their fields. What that brings in, and what I hope to develop, not just for my career, but I think for studying sickle cell as a whole is this not only awareness, but this toolkit for myself and for sickle cell disease as well as this database and kind of our approach and what we're looking at, and how we're looking at it, and then hopefully gain insight into why certain things are happening in sickle cell disease to the heart. Then obviously from there the end goal is always, how do we prevent it? Or how do we treat it when it happens? You know my work is very multidisciplinary and collaborative, and I think cardiology, for a very long time, has been focused on classic heart conditions. But it's important to recognize that it's a wide field. Now that we have these intersections with other fields in medicine, things are starting to get very exciting. You know, cardio-oncology, women's health now is a very big issue- and should have been for a very long time. Sickle cell disease, I think, still has a lot more that can be done there for heart doctors. There's a lot a lot to do and a lot of work and a lot of good. And you have the potential to impact 25 to 35 million people worldwide. That's huge.
09:22 VO:
Thinking about the translational science underpinning this study, I asked Dr. Tofovic if aspects of the project, including the S(CD) Squared database, could be generalized or repurposed for those studying other diseases in the sickle cell patient population- or even other rare diseases.
09:42 Tofovic:
I think that's one of the major goals, and that's why my team, and my mentors and everybody else who's been involved has spent so much time in building the SCD Squared database. What we're hoping to do here is to expand that and to keep and preserve it for later generations as well as for collaborators and other sites, and within our own institution. The hope is also that some of the methods that we're using to approach the study of sickle cell disease do get validated within our data set, and then we can expand those to other datasets for further validation. I mentioned the challenge of studying rare diseases is there's not as many patients in a single site, and sickle cell disease also has a lot of other challenges. Individuals sometimes will jump in between centers, because when a crisis happens, they have to go immediately for care. There is also a very much the high influence of social determinants of health in sickle cell disease. Many of these patients do not get the access to care that more affluent individuals will receive. The goal here is to just create the sphere of this is how we can approach this group. These are the toolkits that we can use. We want others to eventually use these tools and these toolkits, and informatics is not a not a bad way to approach it. And also, the second half of this is creating a biobank or biorepository of samples from those that decide to participate, or would like to participate, within our state. Those samples are then going to be available to collaborators, to future generations, individuals at other sites to answer other questions, getting better knowledge of how does sickle cell disease affect the lungs? And what is happening in the kidneys? And I'm one person. My team is still only a handful to two handfuls of individuals. Even with trainees and mentees and research coordinators and everybody who comes in and works, we're still a small team in the grand scheme of scientific inquiry in the world. So that is one hundred percent the goal.
11:32 VO:
As we concluded our conversation, I asked Dr. Tofovic about how he hopes to leverage the KL2 award to advance his career as a translational scientist- and what that career might look like a decade from now.
11:47 Tofovic:
Number one, it's to create this clinical and sample biorepository for myself, for other collaborators and future generations to study. And then build up the methods to analyze it. That is exactly what the KL2 is funding. As I mentioned earlier, I have much bench to translational research expertise. But when you study rare diseases in 2024, that's just not sufficient. You've got better tools to help bring in patients to help study patients longitudinally, to make sure that we get a more complete picture of what's happening to those individuals. And so, for myself and what I really hope is two-fold. One is just a deeper understanding of the methods utilized to really recognize the patterns and clustering of what's happening. And is there groups? Are we seeing phenomenon in these individuals that we haven't recognized before? Along that route, I'm developing my own informatics- health informatics, bioinformatics- background. There's this saying, “bad data in means bad research out or bad data out.” We have to be very careful when studying in large scales like this. We’re basically looking at numbers and some outcomes. And those outcomes are basically a 0 and a 1. And there's people that that represents underneath. On top of that, we have to be very careful about the data that we're analyzing and how that data is collected because most of our data goes through someone's hands. And that data itself has bias, and that data, and how it’s viewed afterwards can also have bias. And as we get into this blossoming age of informatics, we really have to be cognizant and aware that the systems that we're developing can kind of continue and perpetuate the biases that we have.
Where I see myself in ten years is really just the natural progression of where I am currently. I wear a couple of different hats within my division, and in this university, but those hats still tailor into bringing and expanding clinical and translational and bench research opportunities to those who haven't been studied, right? Who haven't gotten access to that, because with every new tool that we develop with every progress made in science, if it doesn't get applied to everybody then you're missing opportunities. We keep talking about a healthcare gap and that certain individuals get more access to care, but the same thing is happening in the research world. There's a research gap, right? Certain individuals get access to research opportunities, the ability to participate in research, and others don't. So, my career goal has always been to study that and develop what I call minimally invasive or minimally obtrusive methods for research participation and that are culturally competent, that are socially competent, to make sure that we adequately represent everybody within research. And that that's exactly what I want to do. That's exactly where I want to be. I am almost positive that I will still be working on sickle cell disease research in ten years. I don't think sickle cell disease is going away anywhere anytime soon, unfortunately, we still have a lot of work to do with it.
14:55 Voice Over, Closing Credits:
Collaborative Endeavors is written and produced by me, Lauren Rieger, on behalf of the Center for Clinical and Translational Science (AKA the CCTS) at the University of Illinois Chicago.
To learn more about Dr. David Tofovic and the CCTS’s KL2 CATS and CATS affiliate program, visit the links in our show notes.
The CCTS is supported by the National Institutes of Health’s National Center for Advancing Translational Science through their Clinical and Translational Science Award. Opinions expressed by guests of the show are their own and do not necessarily represent the views of myself, the CCTS or our funding agencies.
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