Welcome to today's AOSSM Research Showcase webinar. My name is Andrew Sheean from the Brooke Army Medical Center in San Antonio, Texas, and a member of the AOSSM Research Committee. I'm excited today to be moderating today's session with Dr. Tad Kremen from the University of California, Los Angeles. Dr. Kremen is an Assistant Professor of Orthopedic Surgery at UCLA. He's an accomplished clinician scientist, and we're really excited today to be talking to him about his experience as a former AOSSM Stephen Arnoczky Young Investigator Grant Award winner. The goal of today's webinar is to provide our listeners with an overview of the types of research that the AOSSM has supported, and the ways in which these awards have provided a stepping stone for researchers to do great things in the realm of clinical and basic science research. Tad, welcome to the webinar. Thank you, Andy, and thank you to the AOSSM for an opportunity to share some of my work. I'm going to share my screen. Okay, hopefully everyone can see that. So yeah, I'm going to talk about my experiences with the Young Investigator Grant. I was awarded the AOSSM Young Investigator Grant in 2015. I am currently an assistant professor in residence at the David Geffen School of Medicine at UCLA, and I'm in the Department of Orthopedic Surgery. These are my disclosures, and these are some of my funding agencies. So tonight, I'd like to discuss my research interests, my specific research question that I conducted my Young Investigator Grant on. I'll review the application process and some nuances that you may or may not be aware of, and I'll also discuss my proposed project, how I executed it, as well as things that stemmed off of that and touch upon some of that. So obviously, I'm interested in sports medicine. I think of this as more of the soft tissue, musculoskeletal injuries, as opposed to the traditional orthopedic bone injuries. I am interested in regenerative medicine. I think that'll be focusing on the biology of healing is really probably the hallmark of my generation of orthopedic surgeons, as opposed to implants. That involves stem cells, a bit of an ambiguous term, but part of my project, I specifically worked on mesenchymal progenitor cells, and I have an interest in other progenitor cells like iPS cells. I'm also interested in novel growth factors and growth factor delivery strategies, and I actually have a matrix scaffolds, which I'll speak a little bit about. So this was my Young Investigator Grant question. I was curious about what happens to these therapeutic stem cells when we apply them to these soft tissue injuries. Do they survive? If so, how long do they survive? Do they actually proliferate? Do they metastasize? Do the genes that we manipulate them to express, do they continue to express those once you put them in vivo? Obviously, that has some therapeutic implications, and is the approach we're using to track these things or answer some of these questions, is that feasible in humans? It doesn't really do us much good if it only works in rodents. So this is the application process. This is off of this year's grant information page for ASSM, and currently there's a basic science track and a clinical track, which is good. That means it's growing, and when I applied for this in 2014, there was just one award. There is a pre-proposal aspect of this grant, which is analogous to what other funding mechanisms call a letter of intent, and then the full proposal, and you find out whether or not you were awarded the grant, and so on once later. But before you apply, you really want to identify what kind of resources you have at your disposal. So is there any kind of internal funding or perhaps philanthropic funding that's available to you to try and help you execute this award or obtain some preliminary data for the award? Is there equipment at your facility or a facility of access to you that you can use to help you execute your project, like core facilities, et cetera? And really try to identify some mentors. If you have some research experience, but not much, it's very helpful to have someone who has navigated this pathway in the past and can help you with little nuances and details to guide you through how to execute things at your specific institution, or maybe they're not at your institution, but they know a lot about the process. Identifying mentors can be, at least in my opinion, highly, highly recommended and will facilitate executing these things. I would start as early as possible, and I'll touch upon why that is. So when you start your application, you kind of brainstorm of how you want to try and answer your question. As I mentioned, at least for this funding mechanism, there's a pre-application, which is similar to an LOI, and then you get invited to submit your full proposal, and you follow a specific format with some of these bullet points here. What I will say that's not explicitly noted, if you don't know this, when I applied for this, I guess I did know about it, but it's very, very important, is that you've got to have some kind of preliminary data. There's got to be some pilot experiment that indicates that this work is feasible and that your results are possible, or that you can actually execute this in your hands at your institution. Having some preliminary data really helps, and that's one of the reasons why you have to start early, is because you need some time to generate that preliminary data before you draft your proposal and go through this process. So this was my specific project that I submitted in 2014 and was awarded in 2015. It's called Novel-in-Vivo Nuclear Imaging of Stem Cells and Tendon Regeneration. So I went through the pre-application process, was invited for a full proposal, and I got my notice of award. Well, one thing I wanted to mention about that is there are some potential administrative or logistic challenges that might arise. For example, if you are at an institution that requires indirect fees for any kind of funding, regardless of the source, and your funding mechanism doesn't have money set aside for those indirect fees, well, now you have to come up with that indirect cost. And it's different at different institutions, so be aware that that's something you might need to navigate. Did you ask for protected time, or did you negotiate protected time as part of your day-to-day life? And not every project can be executed on weekends and nights, so you've got to have a strategy for how you're going to address that challenge. I had the, I guess, fortunate challenge of getting awarded a Orthopedic Research and Education Foundation Young and New Investigator Award at the same exact time that I got the AOSSM Young Investigator Grant. So now I had two projects to conduct while I was in my board's collection and nearly in practice and trying to navigate a number of hurdles. So be aware that it's not just getting a grant out the door, there's a lot of downstream things that you may have to navigate. So this was my proposed project, so I was, we were going to use some specialized radioactive probes to track therapeutic stem cells in vivo. We're using a rat tendon defect model. The imaging equipment that was really essential to my project was this Microspect CT scanner as well as an MRI. But after I had executed my contract to conduct the work, there was a catastrophic failure of the Microspect CT and to repair it was $500,000. So time went by and the institution was evaluating whether or not it made sense to invest in this apparatus for either myself and other investigators. Ultimately, it was not fixed and so I didn't have a piece of equipment that was essential to my proposal. So I had to pivot in my, I didn't want to give up my research question or the ways that I, the questions that I wanted to answer, you know, I wanted to see if the cells survived, did they proliferate, is it feasible on humans. So I pivoted and I decided to look at iron oxide nanoparticle labeling of cells and image those by a micro MRI. Again, a non-invasive clinically applicable technology. So what I didn't have is preliminary data. The good news is I already had the funding, so I didn't have to convince reviewers that I could do this even though I had no experience actually doing it. And what I relied on was data from other disciplines. And this is a common theme in orthopedics where you can repurpose some technology that maybe wasn't designed for musculoskeletal environments and apply them to technologies that could actually be applied in something relevant to sports medicine. So there was evidence for this in cardiac disease and using stem cells to treat that. So this is a picture in a paper describing this in 2010 where they, you can see these low signal intensity areas by the black arrows that are labeled stem cells in a rodent heart. So I felt like it was a reasonable approach that allowed me to still answer my question in a clinically relevant manner. So this is what we decided to do. We took our mouse mesenchymal stem cells and we engineered them to express the separase, which allowed me to detect bioluminescence whenever those cells are alive and making luciferase so you can detect their presence just through the soft tissue envelope of a rodent using bioluminescence. And we applied, we used an Achilles tendon defect model. This is what this picture is, is about a two or three millimeter defect in the rat Achilles tendon. Ten animals, five animals received these transgenic cells which were labeled with superparamagnetic iron oxide nanoparticles and five animals got the transgenic cells that were not labeled with the iron oxide nanoparticles. We looked at bioluminescence or transgene and we also looked at micro MR imaging for these iron particles. We imaged them at a week, two weeks, and four weeks. We did our statistical comparisons and looked at the histology. The histology we stained for Prussian blue, which stains blue of any iron deposits that are there, and we used immunohistochemistry for the separase as well. This is what we found. So we implanted the cells at one week out. We saw that this bioluminescence signal was the same in both the iron nanoparticle and the non-nanoparticle labeled cells. And this is just some examples of a zoomed in area of the rat Achilles showing our bioluminescence. And at two weeks, we actually had a greater increase in the bioluminescence, indicating that the cells may be actually expanding. And the presence was even there, the signal was even present at four weeks, and it was above our initial seven day level. So we were impressed that the implanted cells not only survived, but they actually proliferated. They were detectable up to four weeks, and this iron oxide nanoparticle labeling didn't seem to affect their survival. This is what the imaging looked like. So if you, on the left here with these yellow arrows, these are iron oxide nanoparticle labeled mosaic homoprogenitor cells in the tendon defect at seven days, two weeks, four weeks. And then you can see in unlabeled cells, there's no nanoparticle cells in the tendon defect in the rat MRI here on the right. So it looked like this approach was reasonable to localize them in a non-invasive way up to four weeks after implantation and setting up a tendon injury. We looked at histology. So again, this is HMU Prussian blue staining. The tissue at low magnification looks tendon-like at high magnification, also very tendon-like, not tendon, but tendon-like. And when you look at the Prussian blue staining for these iron oxide nanoparticle labeled cells, they localize at the tendon defect site. And so it suggests that these labeling strategy does not affect the differentiation of these cells in the tendon-like tissue, and it is very similar between the two groups. When we looked at luciferase staining and histochemistry, these green labelings, the luciferase positive cells in both the iron oxide labeled and unlabeled, and you can see that at the defect site that co-localizes where that Prussian blue staining is, you also see this luciferase staining indicating that these cells survived, they expressed their transgene for at least four weeks. And really, the location of these cells and histologic appearance indicates that these cells are probably contributing to some kind of tendon regeneration. So MRI of exogenous transgenic mesenchymal progenitor cells labeled with this iron oxide nanoparticle seemed to allow for in vivo localization and assessment of retention of cells in the setting of tendon regeneration for at least four weeks. And the nanoparticles didn't seem to affect cell survival or transgene expression. And then this work you can see is published in American Journal of Sports Medicine 2019. So what stemmed from that? So we were curious about maybe doing something a little more translationally relevant. Rats is all well and good, but how about human cells in a large animal model? So we picked a pig ACL transection post-traumatic osteoarthritis model. We used a little bit different version of our iron oxide nanoparticles, but same basic idea. And in this case, it was human cells delivered into the knee joint percutaneously after a pig ACL transection. This is the experimental design. So we got our human bone marrow cells. We isolated our mesenchymal progenitors. We transduced them with luciferase to get them to express our luciferase transgene. The iron nanoparticles in this case were the nanoparticles covalently bound to a fluorochrome so we could image it with both fluorescence as well as MRI. And we also used a different fluorescent dye strategy, this DII, which is interrelated to the cell membrane of cells, not specifically. And then we tested it at time zero and at two weeks after implantation. So we first just wanted to see if we could image these cells. So we did our surgery, injected the cells, injected our luciferin substrate, and detected bioluminescence. So then our question was, OK, this technique seems to work. What happens if we implant the cells and then try to image them two weeks following implantation? This is what we saw from a histologic standpoint, just demonstrating that this is indeed a model of post-traumatic osteoarthritis. By the time we get to three weeks, you have pretty advanced chondromalacia. And imaging-wise, this is what we found. So this is a fluoroscopic image of our fluoroscopic-guided intraarticular injections. We injected some contrast, made sure we're on the joint. Then we injected our cells. When we added luciferin, you see this bioluminescence signal detected. So we determined that this number of cells imaged in this fashion was feasible. So then we did the same thing, where we did an ACL transsection, percutaneous injection of our cells. And then we followed them for two weeks after the injection of the cells. So at week two, our membrane died. We saw a great fluorescent signal. Our iron oxide particle coupled to a fluorochrome. We saw a great signal localized exactly where we did the injection previously. And this correlated well with our bioluminescence signal, as well as our MRI signature of these low-signal-intensity iron oxide particles. So we felt like this was a pretty good ground-level study, just demonstrating that we have a large animal model. We can use human cells and evaluate some human cell therapies in a large animal model that's able to be translated to the clinic in a late translational fashion, as opposed to a smaller animal model. Part of this project involved looking at some biomarkers. So interleukin-1 beta goes up in these synovial fluid of these animals. And by two or three weeks, it's really teetered down. We also evaluated these things in serum and urine. But what was interesting was that when you compare this to what people have reported with acute or early subacute, late subacute, and chronic arthrocentesis specimens, it really matches up where they see this acute IL-1 beta increase after an ACL injury. So it's a degree with which they will see in humans. Also looked at biomarkers, which is type 2 collagen breakdown products. And you see that it increases over time and then kind of normal or plateaus. And we looked at this also in the serum and the urine. And when you look at data on the placebo group of this Latterman study, where they were looking at placebo versus cortisone injected into acute ACLs, it's a similar pattern of expression in the placebo group to our ACL-injured pig. So again, this recapitulates a human disease in a large animal model. So from that biomarker data, I was actually able to have some sufficient preliminary data to apply for and get awarded an ORIF prospective clinical trial grant, which I have going on right now. We're looking at saline versus recombinant human interleukin-1 receptor antagonist injected into a knee after acute ACL in an effort to try and prevent downstream post-traumatic osteoarthritis. And we're looking at patient-reported outcomes, some biomarker data, as well as some specialized cartilage-sensitive MRI approaches. And you can read more about that on this clinicaltrials.gov site. From that, I was able to be awarded even further funding in this PTOA space. And I was awarded the 2023 ORIF Injectable Orthobiologics Knee Osteoarthritis grant for some work related to this, which is sort of the latest funding. Another thing that stemmed from my AOSSM Young Investigator grant was, you remember this collagen sponge I was talking about and this defect and the histologic appearance of this tendon-like healing in this tendon defect? Well, that's very different than what I've noticed or what people have reported in soft tissue to bone healing. So this is a panel, these four panels here is an uninjured native enthesis on the left and then a tendon repair on the right. And on the left, you see that there's this elegant transition of tendon fibrocartilage to bone. When you look at it with polarized light, these are well-aligned fibers and collagen. As opposed to a healed tendon repair has no fibrocartilage in this disorganized scar ball between the tendon and the bone. When you look at it with polarized light, it's just very disorganized collagen fibers. So why is that? Well, I looked up some of the biomechanical properties of this type one collagen sponge and it ended up being nearly identical to a native tendon. So I thought perhaps this matrix can help guide the cells toward a particular differentiation phenotype. And so that ended up being something that others had thought about as well. And so when you look at people on the bioprinting and engineering space, they're able to make a matrix or a bio-ink that can stimulate mesenchymal stem cells to become something like bone. You can make something that's a matrix similar to tendon that can push these mesenchymal stem cells to become tendon-like. And you can tinker with a number of biomechanical properties of these various substrates or bio-inks by changing mineral content or photocrosslinking to get biomechanical parameter changes or Young's modulus of elasticity changes. So the idea was can we make a extracellular matrix scaffold that can help push cells towards a specific phenotype and in our case recapitulate the mechanical properties of a enthesis so that these resident progenitor cells may be able to differentiate in the cell types required at the enthesis. So this has been, or this is one of the aims of my ongoing career development award. Also of interest from this work, I became interested in growth factor delivery. Right now we sort of sprinkle on growth factors like BMQ2 at the time of surgery, which is a time zero. We can't deliver a growth factor after that. It's a super physiologic dose that has a number of complications associated with it. Ectopic bone and seroma and airway compromise, which is what you see here on this image as well as ectopic bone at the greater tuberosity here in this study. And so how do we get growth factor delivered to this soft tissue bone interface and how do we do it at times after the time of surgery? Well, we investigated a one approach, which is to use bisphosphonates as chaperones for these bioactive molecules. Bisphosphonates have a natural affinity for hydroxyapatite and the calcium in hydroxyapatite, which is when you have unexposed hydroxyapatite in bone minerals, that's an abundant source of that. And the bisphosphonates just naturally attract that area. And there are commercially available bisphosphonates or chrome-bound molecules. And so what we did is decided to use one of these fluorochrome bisphosphonate molecules in the setting of a tendon repair model. So we transacted the Achilles tendon off of the calcaneus, took a dental bur to stir up a little healing and expose cancellous bone and hydroxyapatite residues and repaired that tendon down the bone. And before we closed the wound, we either applied local compound directly onto the tendon bone repair site and then closed the wound, or we closed the wound and injected systemically intraperitoneal injection of our study compound after the wound closure, and then took them over for fluorescence imaging. This is what we found. So over time, for at least a couple of weeks, you see this increased signal directly localizing at the site of tendon repair. And the local administration and the systemic administration were nearly equivalent at all time points. And the repair groups were elevated signal above the sham groups at all time points. So you do get some signal off target with these at a much, much lower level, as you can see from the graft at the contralateral extremity, but there's absolutely no signal at the repair site on this sham animal. We'll just get a skin incision. So we're trying to make this more specific. And one of my colleagues had developed a molecule they were looking at bone turnover called OFS3. And what it is, is a bisphosphonate bound to a fluorochrome, but it's also bound to a quencher. So the fluorochrome, even when it's excited, cannot emit light as long as the quencher is around. But the quencher was attached to the molecule by a amino acid sequence that was cathepsin case sensitive. So if you take this molecule and you expose it to activated osteoclasts with a secreted cathepsin K, then the quencher gets digested away from the bisphosphonate and the fluorochrome can now emit light. And we know that osteoclasts are present at the site of tendon bone healing. So similar approach, we used our rodent Achilles tendon to bone model, and we either applied the OFS3 directly to the wound before we closed, or we closed the wound and injected the intraperitoneally, and we compared that to our sham animals. And again, we saw repair was better than sham at all time points, and there was no difference between local or systemic injection. So that's all well and good, but hopefully we don't cause harm with our compound here. So bisphosphonates are often used to inhibit osteoclasts. So we want to know, can these things impair healing? We look at cathepsin K activity in an uninjured model. You don't see much there, but with our Achilles tendon model, our Achilles repair model, where we burr down some bone at this site of repair, this is where the suture was post-op day four, so it hasn't healed yet, as you can see, but you do see abundant immunohistochemistry standing for cathepsin K, indicating that this mechanism is a realistic pathway to target. And when you look at healing over six weeks, which is a reasonable timeframe for a rodent Achilles to heal, you don't see any difference on H and E at six weeks, and you don't see any difference between the OFS3 treated and the just repair group without our study drug. There's no difference in cathepsin K stains. It doesn't seem to impair osteoclasts or the overall structure of the healing tendon. So I'll stop there, and I'll just summarize that I think research is exciting. You can help us answer some questions, including ones that are clinically relevant. And for me specifically, the AOSSM Young Investigator Grant was a really important starter of my research career and really an essential stepping stone for me as well as other people. And I think if you end up taking that first step along the pathway, you'll end up realizing that you can do some exciting things, and if you follow the science, it'll probably take you in ways that you didn't necessarily plan on. At least that was the experience for me is I never imagined I would get these other grants and be taken down this road that I've been down, but I've been very lucky, and it's been very exciting, and I'm looking forward to continuing along this pathway. But with that, I'll just say thank you to, this is not all of my mentors, but just some of them, and my lab group, I couldn't have done this work without the help of some very talented mentors and technicians in my lab and various trainees at various levels. And certainly I wanna thank all of my sponsors, and RAF, ASBMR, the NIH, and certainly the VA, but also a big thank you to the AOSSM, which really helped start my research career. So with that, I'll turn it over to Andy, and I'm happy to answer any questions that you might have. Tad, thanks so much for that fantastic presentation. As a former AOSSM Sandy Kirkley Clinical Outcome Research Grant winner, a lot of what you said resonated with me from the standpoint of how one goes about undertaking research. Certainly, I'm sure a lot of our listeners are interested into your development and your trajectory as a clinician scientist. So I have a couple of questions here that I thought could be springboards for maybe you could elaborate on some of the things that you've discussed. In your introductory remarks, you rightly identified the importance of understanding the resources available to you at the time of writing your grant proposal. Can you describe what your enterprise looked like at the time that you were putting your proposal together? And also give the listeners a feel as to how this award helped take things to the next level and what your research team looks like today. Yeah, so I'm just about 10 years into my career as an attending orthopedic surgeon. The first five years, I was at an institution that was more of a sort of hospital employee or private academics sort of environment. And whereas now I'm at more of a sort of a classic academic program. So one difference when I first started in my first role was the availability of, or this role of project scientist was more of a thing at my first institution. And those individuals were people who had completed their PhD, maybe even a postdoc somewhere, and they were installed into a position where their funding came from multiple investigators or institutes and departments. And they were already in-house and sort of willing to work with you to do some projects as opposed to sort of the classic academic postdoc environment where they're usually working for one PI and sort of one project. So for me, it was great because I did not have the resources to go out and afford to hire a full-time postdoc dedicated to my project and hire them and train them and et cetera. So that was one difference is the availability of these project scientists in the environment I was in previously was actually beneficial when I was first starting out because it had a little bit of sort of pre-plug and play infrastructure for lack of a better term. The other difference I would say is trainees. So when I was at my previous sort of hospital employee model we didn't have medical students, we didn't have undergraduate volunteers and we were very much technician dependent. Whereas now we have sort of a number of individuals right on campus who are interested in participating in research. And then finally, I guess the biggest difference is probably that in previously I had really one group of core musculoskeletal researchers, like really one lab. And now I am at a institution that has multiple heavily funded musculoskeletal researchers. In addition to being on campus with sort of a very big engineering, chemistry, imaging and pharmacology department at UCLA. So those are, I guess the differences between my previous experience and what I have now. Well, it sounds like you have a fantastic collection of resources there. You concluded your presentation by thanking a number of individuals especially some senior mentors and scientists. And I think for those researchers that are just getting underway, it's really important obviously to have mentors and people that can help you and fill in the blanks so to speak when you're getting everything started. The relationships that you have now with those senior scientists and those researchers did those exist prior to your proposal or are those things that you established subsequent to coming up with your study design and putting your proposal together? Yeah, I would say a little bit of both. At my original position when I was first proposing and then conducting the Young Investigator Grant Project, like I said, there was one group. So I naturally, one basic science musculoskeletal group. So I naturally kind of gravitated to that group almost out of necessity. Whereas even before that, when I was in residency I had taken a year of dedicated research and I worked in Karen Lyon's lab who is now sort of my closest collaborator and at UCLA where we have joint lab meetings and a number of individuals are involved in both laboratories activities. So when I came back to UCLA where I trained in residency and had done my research fellowship and I had continued my relationship with the mentors I had during my residency but coming back and having people like Karen Lyons and John Adams was, I guess, set up ahead of time. And then as my projects grew, I ended up as I mentioned in the talk, we developed some of my colleagues had developed a molecule looking at bone turnover imaging and I worked with them to sort of repurpose that and got some new mentors working on that specific project. And then things just sort of grow and you keep the original mentors you had and get new projects based on where the science takes it. But I think a key thing, and for me, at least I was struck by when I was listening to your talk and then, you know, as we have this conversation now it's a lot about adapting your interests to the environment in which you find yourself in. And it seems like you've done a great job doing that. And I think the proof is in the pudding in terms of the output of all of your efforts. Yeah, I think the common thread there is everybody's excited about the science. And so people in general are very excited to work with you especially if you have something that's gonna work on a clinical problem and very feasible. So I think it's pretty easy to get people excited about something. I think a lot of young investigators out there struggle with figuring out how to define themselves in terms of what their professional role is. I think the term clinician scholar is used a lot. And I think early on, certainly this has been my experience is I've struggled with to what extent am I a clinician with a big C and a scientist with a little S or vice versa? How have you gone about developing your career in the way that you've set up your professional existence allocating the requisite amount of time for clinical activities, scholarly and research related activities? How do you think about it? Yeah, certainly a challenge as you're well aware. I do think at least early in your career, yes, there are a lot of challenges you gotta navigate. There's developing your clinical practice. You're in probably in boards collection. You're really learning how to operate without having an attending helping you out or an army of residents to help you out. But there's definitely some downtime as well. And even in a city or particularly in a city like Los Angeles where there's plenty of orthopedic surgeons around. So you're gonna have some downtime to think about your research interests. I also think it probably is a little different if you're doing basic science research versus clinical. So if you're doing basic science research I think you almost need to start very early in your career as an attending. When you get out into practice it's very easy to put your head down, start seeing patients and hop on that clinical treadmill of seeing patients getting very busy clinically. And at some point you stop to look up and you realize maybe years have gone by and literally all of your time is occupied. So at that point, I think you could find yourself kind of disconnected with the research infrastructure and it can be hard to bridge that gap to do basic science research. Whereas if you started doing it even just a small amount early I think having that small sort of toe in the pond of research, you might find that that project can grow legs and take off. So I guess my inclination would be to just have a small research presence if you're even partially interested and that way you can decide to do with it what you want as things evolve. Yeah, so, and to follow on, what's a normal week look like for you in terms of protected time? What are the nuts and bolts of ways in which that you're able to make all of this work and be a clinician and then do all the great research work that you've talked about today? Yeah, well, I don't think clinicians have a 40 hour work week. I think you know that. And regardless of whether you're doing research or not having a nine to five job as a physician especially as a physician surgeon is sort of a mythical unicorn. So for most of us, our days start pretty early whether it's 6.30, 6.00 AM particularly on operating room days. So I think most of our work weeks are probably like a 60 hour work week or so. And that would be true for me. And so I spend about half that time doing research and half that time doing clinic. I have the luxury of being funded by a career development award which allows me to have that protected time. Not every situation is like that. And certainly life doesn't fit into a box meaning my clinical activities certainly bleed into my research time. And yeah, that means my research time will bleed into my nights and weekends at times but you absolutely just have to make a conscious effort not to neglect one for the other. And at this point I've been doing it long enough but it feels much easier than when I started. But I think that's an eternal struggle that it's keeping that balance is a challenge but it does get easier as time goes on in my experience. Well, I gotta say, I think that what you presented today and the things that we've talked about and the candor with which you've spoken about being a clinician scholar these are all aspirational for me I'm sure for our listeners out there. And so it's been my overwhelming pleasure to be involved in putting this webinar together with you. And on behalf of the AOSSM Research Committee it's just so great to see that these types of awards and how the society supports our members what the yield of that is in terms of this award that you got way back when has overwhelmingly had a positive impact on your trajectory as a researcher, which I really think it's all about. So thanks again so much for participating. Yeah, well, thank you for taking the time to discuss these things with me and listen to my talk. And I'm sort of excited to do this maybe 10 years from now we can see where we both are but I definitely would again like to really thank the AOSSM for, I guess, believing in me and investing in me early in my career because it's definitely a huge benefit and great thing for our members. Well, Tad, thanks again. And thanks so much to everybody that tuned in for this edition of the AOSSM Research Showcase webinar. I'm sure you all got as much out of it as I did and hope you have a good rest of the day.

webinar

Dr. Tad Kremen

AOSSM

Stephen Arnosky Young Investigator Grant Award

sports medicine

regenerative medicine

stem cells

soft tissue injuries