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Dr. Anantha Shekhar and Translating Research into Treatments


Welcome back to the healthcare triage podcast. This podcast is sponsored by Indiana University. School of Medicine whose mission is to advance health in the state of Indiana and beyond promoting innovation and excellence in education. Research patient. Care. I you school of Medicine. 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 a NAMPA Shaker. He is the executive. Associate Dean for Research at Indiana University School of Medicine as well as the director of the Indiana see. Tsi or clinical translational research institute. I should say I'm just full disclosure. He's 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 an answer. Welcome thank you. We'd like to start off actually buy off talking to our guests about how you got to this position Sort of what got you interested in medicine. What got you interested in research and then sort of. What eventually brought you to to position today. Both I'd say executive Associate Dean Research and and headed the seat. Gsi Yeah it's You know it's an interesting journey when you look back Probably started when I was in high school. Began to Have interested 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 you know essentially go through chemotherapy and passed away. And that SORTA got me really interested in understanding the brain understanding neurosciences and medicine. So that's That started the journey. And so I became a doctor became a neuroscientist and most of my research is focused on that area. I came to I you as a as a resident they had a special program for residency PhD in neuroscience. So that's how I got to Indiana University and then would finished my residency here By during the time of his doing research and was essentially God my first star one as a resident in ended up joining here as a faculty and have staged for thirty years since then So most of my work has been in neuro psychiatric disorders trying to understand but 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 clinical research unit on lists You know doing a various types of administration As head of Adult Psychiatry so at that point about Let's say twelve years ago The Dean sort of approached me Dr Braider was the Dean then he he approached me to see if I would be interested in writing this new grant called the TSA grant He said Oh you do basic research or do clinical research. You would 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 we 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. The state committee talk a bit about what what is translational research? Because we've mentioned a couple of times on the show before but you probably better than anyone else's prepared to actually explain What is it? Yeah so translational. Research really spans. A broad Sort of space of biomedical research. Would we 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 war. 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 is our 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 war 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. So free search or what? I would call translational researchers. I find when I talked to the general public about this. That surprised that this isn't even an issue. Like why weren't we doing that always Why do you think it is that it took until say twelve years ago before? There were major initiatives to do that. Yeah I think. Part of it is just the way Researchers are trained and research as Walt Lord of the basic in discoveries and fundamental research occurs in what we would call the traditional scientific laboratories where people are working on cells or small animals or you know various different organisms that are not humans and then at the other end you have clinicians who are working with patients or trying to treat patients or trying to understand diseases and these two worlds were never fully integrated because the 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 or PhD's 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 Verses University laboratories are quite different. So I think a lot of this was just the way. We had sort of organized biology science and medicine With I think was a big problem so little more than a decade ago the NIH decided. We needed to do better. And the major way. I think we decided to do that was through which is called. C. T. essays. Can you talk a bit about that? And what they're supposed to do. Yeah so in In the nearby about fifteen years ago then National Institute of Health Director decided that this this silo of basic discovery and clinical research Is is a problem and we. They needed to create a large program. That connects the two. So what they proposed was Something called clinical and translational science awards. That will be given to Sort of leading medical centers very similar to the cancer center concept that they would find 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 is congressionally mandated program There's you know significant dedicated funds And over the last ten years they've now funded about sixty or so medical centers and each of them. are now mandated just like Indiana clinical and translational science institute to really connect discovery to people's health. How do we do that? What what what? What does the PSI House it? Setup and what are its major activities to try to get that done yeah so a typical see TSA or act SL has these in a standard Platforms for helping to make this happen. One of their biggest sort of I would say impact is is trying to create standardize way of studying and engaging patients in 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 that's limited way. We can make progress in medicine so Ct assays are dedicated to building infrastructure. For that and enhancing community engagement to improve participation. A second area that see. Tsa's are very dedicated to really training the next generation of scientists. So one of the major focus point of that is to really break down this silo of what I mentioned. You know people being trained differently to do discovery science and trained differently to do clinical research. We need to you know. Make sure that you both of those research types are cross fertilized understand each other better so new training that C. T. assays promote Helps them to become more translational if you will you mentioned community engagement. What are what are some of the things that we're doing in Indiana? Try to make that better. Yeah community engagement is a big challenge in terms of Academic medical centers in 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 in Indiana see. Tsi is really create Programs that specifically connect with community organizations we also partner with community organizations to do pilot projects to dial up. You know various Community focused Research as well as more. Recently we've started to do much more engagement through online connectivity and 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 so in addition to I'd say the partnerships between a U. Notre Dame and purdue. It seems that they're also connections to other organizations. That are not perhaps academic. Could you talk about those a little bit? Yeah absolutely I think. The non academic organizations are also fury important in this In this translational endeavor Agreed example. Is You know if you want to translate a treatment that you've discovered into making into a medicine that can be given to patients. You need the pharmaceutical industry. So one example is lily which is a great company here in Indiana. That's being a partner of this. Etsi 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 I you held Eskenazi health or an example of those kind of partners and then finally we also partner with the state which is a major you know. entity for human health then supporting various types of health initiatives. So we have partnered with the Department of Family and health services to within the State Challenge Wall so those are some examples of non academic partnerships. So this just seems like such utter common sense. Why why doesn't everybody do this or is everybody doing it and doing it in their own? Yeah it is you know. Unfortunately a violent all make sense would the challenges. It takes a lot of effort because everyone's busy. Everyone has their own particular issues. So and they're worried with their particular problems whether it's a hospital giving care or whether it'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 are you know takes this special effort and I guess that's what's Etsi's are doing is to provide that that effort are these spread all over the country they are. They're about sixty or so across the country. there's only one in Indiana but there's many other large medical centers also have them. Do THEY DIFFERENT. Foci or are they all sort of in general. Just broad spectrum transitional research there are some specific focal area so while they all have the major sort of expectations that they'll help Provide clinical research infrastructure and general and train the next generation of researchers they also specialize in some unique thing so for example the the area that. Indiana is well known for is public private partnerships where we can partner with companies partnered 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 you know large. It companies like Google and apple others have partnerships with national laboratories so they're warious types of partnerships. So this speaking of partnerships. It seems like it's a good time to transition to talk about precision health initiative which has also been something we've discussed with. A variety of guests are less program. We talked about Cancer Treatments especially without Sarcoma. So could you give us your description? Sort of what the position health initiative is and and how it's being operationalized. Yeah position. Health Initiative was one of the Grand Challenges for the Indiana University. Bicentennial celebration so what would we proposed about five years ago was that we would create a large program multi-disciplinary program across all of you that would focus on looking at human health differently and the idea was that human health is not just about biology or genetics. But it's in addition to those things. It's also about behavior peoples behavior about people's environment as well as serious 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 have their health so in order to define a person's health we need to get better position 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 and some of these areas such as genetics genomics as well as data sciences a 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 blitz also select some diseases and disease areas where we would actually make some grand challenges if you will wear heels challenge our researchers to think bigger and go for higher scored if goals so 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 those one of them was pediatric Sarcoma. The others were Triple negative breast cancer and multiple myeloma. These are you know. Obviously high goals but We're certainly challenging. Are Reflecting that it's interesting to have this discussion now. Because we've had we've had guests on to talk about all three of those problems we've had We had I think Milan on to talk about triple negative breast coma. We had a guest on to talk about Muslim Aloma Less so so clearly. It's good to have this brought together but I won't even step back for even get to that to talk about you mentioned building infrastructure and so often I'm I'm really moved by the fact that we invest too rarely in that the grants that we can get for me and I H 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. Yes so I mean that's a great question you know as you've mentioned that infrastructure is it's like roads and you know plumbing. Nobody thinks that sexy and nobody wants to invest in it Yet they without those. We can't function so the same way we felt like Indiana in school university Needed some of those Major investments in cutting edge technologies one of the challenges. Is You know technology's changing so fast. That within five years a leading academic medical center can 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 ourselves and you know sell manufacturing facility for a for immunotherapy for example similarly we wanted to discover drugs and new therapeutics that needed major investment in thing slyke electron and various other High end instrumentation that we did not have so. These are things that we've we needed to build that we built with the position health initiative but in addition to just getting equipment and technical kinds of free sources. You also need a lot of Investigators who can actually use it and actually make things out of those So we had to recruit a lot of scientists as well so we ended up recruiting Nearly forty forty two new scientists into I use school of Medicine. And I you can broadly through position health initiative All I to build this kind of scientific capacity and expertise and what are you. What are your hopes for that? Where do you think that'll go? I think it'll go in many different ways. It'll put us in In in great shape for the next ten years to be competitive for a grants and awards to be able to create the next generation of trainees that are trained in this 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 I use. Stand out for the next decade with this. Can you talk a bit about the precision part of precision health Yeah so the position. Part of the precision health is very interesting. It's it's an evolving field and it's still You know there's a lot of unknowns so that 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? So and a great example is Alzheimer's disease It's it's going to be a massive problem for our society in the future and we're already seeing no significant number of people suffering from it We don't fully understand what the disease is how. It's cost wide progresses differently in different people. And what do we do to either prevent or Slow down the progress of the disease. So they're what we're starting with is really very Sort of fundamental research. Were trying to understand. What are some of the mechanisms for Alzheimer's trying to build mouse model? So 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 a For example paediatric 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. What are you most excited about looking towards the future? 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 at in Indiana to the next level and really inspire the next generation of scientists. Ooh think big and to really go for the stars. It's good to have 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 and the community Certainly many of the diseases that we talked about but to sort of 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 to 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 in really thank you for joining us. Thank you thanks Thanks for the conversation was great Sharing this hour with your healthcare trash podcast is sponsored by the School of Medicine whose mission is to advance health mistake of Indiana 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.

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