On this episode of the Healthcare Triage podcast, Aaron is talking to Dr. Anantha Shekhar, founding director of the Indiana Clinical and Translational Sciences Institute (CTSI) and leader of the IU Precision Health Initiative. You’ll learn about the importance of translational research and why personalized medicine is putting researchers on the forefront of future developments in healthcare.
The Healthcare Triage podcast is sponsored by Indiana University School of Medicine whose mission is to advance health in the state of Indiana and beyond by promoting innovation and excellence in education, research and patient care.
IU School of Medicine is leading Indiana University's first grand challenge, the Precision Health Initiative, with bold goals to cure multiple myeloma, triple negative breast cancer and childhood sarcoma and prevent type 2 diabetes and Alzheimer's disease.
Dr. Aaron Carroll: Welcome back to the Healthcare Triage Podcast. This Healthcare Triage Podcast is sponsored by Indiana University's School of Medicine, whose mission is to advance health in the state of Indiana and beyond by promoting innovation and excellence in education, research, and patient care. IU's School of Medicine is leading Indiana University's first grand challenge, the Precision Health Initiative, which we will talk about today, with bold goals to cure multiple myeloma, triple negative breast cancer, and childhood sarcoma and prevent type two diabetes and Alzheimer's disease. Our guest this week is Anantha Shekhar. He is the Executive Associate Dean for Research at Indiana University's School of Medicine, as well as the Director of the Indiana CTSI, or Clinical Translational Research Institute. I should say, just full disclosure, he is also my boss in more than one way, but we're going to be talking today about translational research and the Precision Health Initiative, which we've discussed with various guests in the last few months. So, Anantha, welcome.
Dr. Anantha Shekhar: Thank you.
Dr. Aaron Carroll: We like to start off actually by often talking to our guests about how you got to this position, what got you interested in medicine, what got you interested in research, and then what eventually brought you to the position you're in today, both I'd say Executive Associate Dean of Research and Head of the CTSI.
Dr. Anantha Shekhar: Yeah. It's an interesting journey when you look back. It probably started when I was in high school. I began to have interest in biology and was very interested in learning about human body, but really when I started to focus more on becoming a doctor was when my closest friend in high school was diagnosed with brain tumor and became blind and had to essentially go through chemotherapy and passed away. And that got me really interested in understanding the brain, and understanding neuroscience and medicine. So that started the journey. So I became a doctor, I became a neuroscientist, and most of my research has focused on that area. I came to IU as a resident. They had a special program for residency and PhD in neuroscience. So that's how I got to Indiana University, and then finished my residency here, but during that time, I was doing research and essentially got my first RO-1 as a resident, and ended up joining here as a faculty, and have stayed for 30 years since then.
So most of my work has been in neuropsychiatric disorders, trying to understand both the brain mechanisms as well as how we understand that in the clinical context and developing new treatments. So as part of that, I was running a basic science lab as well as running a clinical research unit, and was doing various types of administration as Head of Adult Psychiatry. So at that point, about I would say 12 years ago, the Dean approached me, Dr. Braider was the Dean then, he approached me to see if I would be interested in writing this new grant called the CTSA Grant. He said, "Oh, you do basic research. You do a clinical research. You'd be in a good position to write this." So that was how I got roped into this, and next thing I know the grant was funded and we decided were going to do this as a translational research platform for the whole state. So we got Purdue involved and then eventually Notre Dame came on board. So all three universities really committed to this vision of creating translational research in the state.
Dr. Aaron Carroll: Can we talk for a bit about, what is translational research? Because we've mentioned it a couple of times on the show before, but you probably better than anyone else is prepared to actually explain, what is it?
Dr. Anantha Shekhar: Yeah. So translational research really spans a broad space of biomedical research. What we've realized in biomedical research is that people can do research at various levels of biology. So there could be, for example, a cancer researcher who studies cancer cells at the cellular level, or there could be a cancer researcher who studies cancer prevention at a statewide prevention program. So you have this enormous breadth of medical research going on. What is missing though, or was missing for a long time, was people who can connect these different levels of research that is going on so that you can take a discovery in the laboratory and bring a treatment to patients, or if there is a successful treatment in patients that is shown to be very effective in a clinical setting and then taking it into policy and into populations. So the people that do that kind of work in the interface of these different levels of research are what I would call translational researchers.
Dr. Aaron Carroll: I find when I talk to the general public about this that they're surprised that this isn't even an issue. Why weren't we doing that always? Why do you think it is that it took until, say, 12 years ago before there were major initiatives to do that?
Dr. Anantha Shekhar: Yeah, I think part of it is just the way researchers are trained and research has evolved. A lot of the basic inner discoveries and fundamental research occurs in what we would call the traditional scientific laboratories, where people are working on cells or small animals, or various different organisms that are not humans. And then, at the other end, you have clinicians who are working with patients who are trying to treat patients or trying to understand diseases. And these two worlds were never fully integrated because people who do clinical work usually are trained as physicians or nurses and have a very different professional background, whereas people who do fundamental research are PhDs and really know their biology and their basic science. So the training is different, their culture is different, and the types of environment they work in. Hospitals versus university laboratories are quite different. So I think a lot of this was just the way we had organized biology, science, and medicine, which I think was a big problem.
Dr. Aaron Carroll: So a little more than a decade ago, the NIH decided that we needed to do better and the major way I think we decided to do that was through which was called CTSAs. Can you talk a bit about that and what they're supposed to do?
Dr. Anantha Shekhar: Yeah. So about 15 years ago, the then National Institute of Health Director decided that this silo of basic discovery and clinical research is a problem and they needed to create a large program that connects the two. So what they proposed was something called clinical and translational science awards that would be given to leading medical centers, very similar to the cancer center concept, that would fund major academic medical centers to create this platform that helps connect clinicians and clinical researchers to basic discovery research. This started as a grant program. It's a very large program. It's a Congressionally mandated program. There's significant dedicated funds, and over the last 10 years, they have now funded about 60 or so medical centers. And each of them are now mandated just like the Indiana Clinical and Translational Science Institute to really connect discovery to people's health.
Dr. Aaron Carroll: How do we do that? What does the CTSI, how's it set up and what are its major activities to try and get that done?
Dr. Anantha Shekhar: Yeah. So a typical CTSA or a CTSI has these standard platforms for helping to make this happen. One of their biggest, I would say, impact is trying to create a standardized way of studying and engaging patients in research. I think the biggest challenge we face as a country is not enough patients are participating in research, participating in learning about their disease, both for themselves, but also for the field and then testing new treatments and new methods to improve their outcomes. So that's a big issue that's limited the way we can make progress in medicine. So CTSAs are dedicated to building infrastructure for that and enhancing community engagement to improve participation.
A second area that CTSAs are very dedicated to is really training the next generation of scientists. So one of the major focus points of that is to really break down this silo of what I mentioned, people being trained differently to do discovery science and trained differently to do clinical research. We need to make sure that both of those research types are cross fertilized and understand each other better so the new training that CTSAs promote helps them to become more translational, if you will.
Dr. Aaron Carroll: You mentioned community engagement, what are some of the things that we're doing in Indiana to try and make that better?
Dr. Anantha Shekhar: Yeah, community engagement is a big challenge in terms of academic medical centers and medicine in general has not been very effective in engaging people in both taking care of their own health, but also helping understand large health problems better. So I think what we need to do and what we have been doing at Indiana CTSI is really create programs that specifically connect with community organizations. We also partner with community organizations to do pilot projects to develop various community focused research, as well as more recently, we have started to do much more engagement through online connectivity as well as social media. So I think there's a lot of effort being put into getting Hoosiers more focused on their own health.
Dr. Aaron Carroll: So in addition to I'd say the partnerships between you and Notre Dame and Purdue, it seems that there are also connections to other organizations that are not perhaps academic. Could you talk about those a little bit?
Dr. Anantha Shekhar: Yeah, absolutely. I think the non-academic organizations are also very important in this translational endeavor. A great example is if you want to translate a treatment that you have discovered into making it into a medicine that can be given to patients, you need the pharmaceutical industry. So one example is Eli Lilly, which is a great company here in Indiana that's been a partner of the CTSI, and they are very important for translating medicines into drugs or products. Similarly, we have connectivity with all of our large health systems, which, of course, provide healthcare to a large number of patients, but also provide the platform for doing clinical research. So IU Health and Eskenazi Health are an example of those kinds of partners. And then finally, we also partner with the state, which is a major entity for human health and supporting various types of health initiatives. So we have partnered with the Department of Family and Health Services within the state as well. So those are some examples of non-academic partnership.
Dr. Aaron Carroll: So this just all seems like such utter common sense. Why doesn't everybody do this? Or is everybody doing it and doing it in their own way?
Dr. Anantha Shekhar: Yeah, it is unfortunately. While it all makes sense, with the challenges, it takes a lot of effort, because everyone's busy, everyone has their own particular issues, and they're worried with their particular problems. Whether it's a hospital giving care or where there's a company making products, they're all busy with their own work and to get out of that box and connect with one another and think of the big picture and the big issues in healthcare takes this special effort. And I guess that's what CTSIs are doing, is to provide that effort.
Dr. Aaron Carroll: Are these spread all over the country?
Dr. Anantha Shekhar: They are. There are about 60 or so across the country. There's only one in Indiana, but there's many other large medical centers also have them.
Dr. Aaron Carroll: Do they have different foci or are they all just in general just broad spectrum translational research?
Dr. Anantha Shekhar: There are some specific focal areas. So while they all have the major expectations that they'll help provide clinical research, infrastructure, and train the next generation of researchers, they also specialize in some unique things. So for example, the area that Indiana is well-known for is public private partnerships, where we can partner with companies, partner with the state, partnering with endowments and foundations to help bring projects forward. But then there are others who have different types of partnerships. Some may have partnership with large IT companies like Google and Apple. Others have partnerships with national laboratories. So there are various types of partnerships.
Dr. Aaron Carroll: So speaking of partnerships, it seems like it's a good time to transition to talk about the Precision Health Initiative, which has also been something we've discussed with a variety of guests. On our last program, we talked about cancer treatments, especially with osteosarcoma. So could you give us your description of what the Precision Health Initiative is and how it's being operationalized?
Dr. Anantha Shekhar: Yeah. Precision Health Initiative was one of the grand challenges for the Indiana University Bicentennial celebration. So what we proposed about five years ago was that we would create a large program, a multidisciplinary program, across all of IU that would focus on looking at human health differently. And the idea was that human health is not just about biology or genetics, but in addition to those things, it's also about behavior, people's behavior about people's environment, as well as various other social determinants of health. So we thought that we should define a person's health not by their physical aspects only, but really this entire spectrum of things that might affect their health. So in order to define a person's health, we need to get better precision about their genetics and their behavior and their environment, et cetera. So that was the big proposal.
But within that proposal, we specifically focused on building capacity in some of these areas, such as genetics or genomics, as well as data sciences, large informatics initiatives, and understanding environmental factors that affect health. So we built very specific programs called pillars to address these. But, again, in order to not just focus on building a lot of infrastructure and not doing anything specifically useful, we said, "Let's also select some diseases and disease areas where we would actually make some grand challenges," if you will, where we challenge our researchers to think bigger and go for higher goals. So the grand challenges we proposed were that we would focus on trying to cure at least one cancer, and then we selected three areas of cancer to try and look for cures. And one of them was pediatric sarcoma. The others were triple negative breast cancer and multiple myeloma. These are obviously high goals, but we're certainly challenging ourselves.
Dr. Aaron Carroll: I'm just reflecting that it's interesting to have this discussion now because we've had guests on to talk about all three of those problems. We've had, I think, Milan on to talk about triple negative breast sarcoma. We had a guest on to talk about a multiple myeloma last time. So clearly it's good to have this all brought together. But I want to even step back before even get to that to talk about, you mentioned building infrastructure. And so often I'm really moved by the fact that we invest too rarely in that. The grants that we can get from the NIH and a lot of the investment is often, here's a project, here's a bit of research, but we so rarely invest in the broad infrastructure, which then allows us to do that kind of work. So could you talk a little bit more about the infrastructure and what we do with that?
Dr. Anantha Shekhar: Yeah. So I mean, that's a great question. As you've mentioned, that infrastructure, it's like roads and plumbing. Nobody thinks that's sexy and nobody wants to invest in it, yet without those we can't function. So the same way we felt like Indiana University needed some of those major investments in cutting edge technologies. One of the challenges is technology's changing so fast that within five years a leading academic medical center can be behind the curve. So we wanted to invest in large scale capacity for doing genomic medicine, which meant that we needed to create facilities that could actually do genome sequencing of patients. We created a facility that could actually make products to be given to patients that are cells and cell manufacturing facility for immunotherapy, for example.
Similarly, we wanted to discover drugs and new therapeutics. That needed major investment in things like electron microscopes and various other high-end instrumentation that we did not have. So these are things that we needed to build that we built with the Precision Health Initiative. But in addition to just getting equipment and technical kinds of resources, you also need a lot of investigators who can use it and actually make things out of those. So we had to recruit a lot of scientists as well. We ended up recruiting nearly 42 new scientists into IU's School of Medicine and ICU broadly through Precision Health Initiative, all that to build this scientific capacity and expertise.
Dr. Aaron Carroll: And what are your hopes for that? Where do you think that'll go?
Dr. Anantha Shekhar: I think it'll go in many different ways. It'll put us in great shape for the next 10 years to be competitive for grants and awards, to be able to create the next generation of trainees that are trained in these novel technologies and that are going to be competitive for jobs in the future. And then most importantly, really finding new treatments and solutions for diseases that we currently can't treat effectively. So I think those are all things that would make IU stand out for the next decade with this.
Dr. Aaron Carroll: Can you talk a bit about the precision part of Precision Health?
Dr. Anantha Shekhar: Yeah. So the precision part of the Precision Health is a very interesting. It's an evolving field and there's a lot of unknowns in that area. Whereas we are learning more about certain types of cancers and we are able to do genetic sequencing of cancer tissue and really tailor appropriate treatment for the genetic mutation in a cancer. That is one of the few exceptions currently. There are many other diseases where we really don't even know what are some of the causes of the disease or what certainly causes complications of those diseases. A great example is Alzheimer's disease. It's going to be a massive problem for our society in the future and we're already seeing a significant number of people suffering from it. We don't fully understand what the disease is, how it's caused, why it progresses differently in different people, and what do we do to either prevent or slow down the progress of the disease?
So there what we're starting with is really very fundamental research. We're trying to understand what are some of the mechanisms for Alzheimer's, trying to build mouse models of those fundamental mechanisms, and then trying to develop new drugs based on those kinds of laboratory models. So it's a very early stage. On the other hand with, for example, pediatric sarcomas, where we can actually take the tissue and do genetic sequencing and find the right mutation and perhaps find the right treatment today, we can already cure patients with some of those diseases.
Dr. Aaron Carroll: What are you most excited about looking towards the future?
Dr. Anantha Shekhar: I'm excited about the possibility of what this could do to our patients. I'm also excited about the possibility that this could take science in Indiana to the next level, and really inspire the next generation of scientists who think big and to really go for the stars.
Dr. Aaron Carroll: It's good to have I think this discussion because so many of the things you mentioned I feel like we've talked about in past episodes, whether it was talking about Alzheimer's or talking about social determinants of health, talking about even smoking prevention in the community, certainly many of the diseases that we talked about. But to get it all wrapped up together to talk about not only how does the Precision Health Initiative and all the ways we're trying to attack these problems matter, in fact, we talked about the infrastructure too. We talked about informatics. We've talked about genomics. But to bring it all together as useful, so can't thank you enough. It's been a pleasure having you and really thank you for joining us.
Dr. Anantha Shekhar: Thank you. Thanks for the conversation. It was great sharing this hour with you.
Dr. Aaron Carroll: Healthcare Triage Podcast is sponsored by IU's School of Medicine, whose mission is to advance health in the state of Indiana and beyond by promoting innovation and excellence in education, research, and patient care. They're also leading the university's first grand challenge, the Precision Health Initiative, with bold goals to cure multiple myeloma, triple negative breast cancer, and childhood sarcoma and prevent type two diabetes and Alzheimer's disease.