Why We Do Research with Sunil Patel, MD, Chip Norris, PhD & Cortney Gensemer

A two-part conversation on how MUSC innovates health care with Drs. Sunil Patel, Russell “Chip” Norris, and doctoral student Cortney Gensemer on Ehlers-Danlos Syndrome.

Dr. Sunil Patel, Chair of the Department of Neurosurgery, and world-renowned neurological surgeon discusses the innovative Zucker Institute for Applied Neurosciences, or ZIAN, a neuro-focused biotech accelerator that aims to jumpstart the development process of medical devices.

Dr. Chip Norris, a basic scientist in the Department of Regenerative Medicine and Cell Biology, and Gensemer, a fourth-year doctoral student and patient, discuss their partnership and research on Ehlers-Danlos syndrome, specifically the hypermobile type which affects 1 in 500 people in the United States.

Read The Transcript

[00:00:04] Loretta Lynch-Reichert: Hello everyone, and welcome to the Medical University of South Carolina’s Science Never Sleeps Podcast. This edition of our podcast highlights a central mission of our academic health center – harnessing the talent, ingenuity, and passion of our research faculty to seek the answers, discover the solutions, and innovate the future. To change what’s possible in biomedical healthcare for those we serve.

And so, we have a two-part discussion. First, Dr. Sunil Patel, Chair of the Department of Neurosurgery, and world-renowned neurological surgeon, will discuss the innovative Zucker Institute for Applied Neurosciences, better known as ZIAN, a neuro-focused biotech accelerator that aims to jumpstart the development process of the medical devices.

The second part of our discussion centers on the life cycle of research discovery. From the basic science laboratory, or bench as we call it, through the translation of that research into clinical care, or as it’s commonly known, the patient bedside. Our guests: Dr. Chip Norris, a basic scientist in the Department of Regenerative Medicine -- the bench, Dr. Patel as clinician representing the translation of discovery, and Gensemer, doctoral student, and patient -- the bedside, showcasing the process that allows MUSC to make a difference in the lives of our communities.

[00:01:31] Lynch-Reichert: First up, Zian. The Zucker Institute for Applied Neurosciences brings together the worlds of engineering and medicine to speed the translation of innovative technology into the clinic, hence the descriptor biotech accelerator. It is a bold and visionary program developed with the Zucker family of Charleston and Dr. Patel. Welcome, Dr. Patel.

[00:01:53] Sunil Patel, MD: Yeah, thank you very much for having me.

[00:01:54] Lynch-Reichert: Dr. Patel, the vision of ZIAN came out of a heartbreaking experience. Can you share its origins and your vision for the institute?

[00:02:03] Patel: Sure. Several years ago, it’s almost 15 years ago, I treated a patient – Mr. Zucker – who suffered from a very bad brain cancer. Mr. Zucker, for those who may know him and those who don’t, was a very innovative businessman and very creative – had over 100 patents himself. And one of the conversations, recurring conversations with him during the last few months of his life with this very fatal cancer, were his frustration with medicine not moving new ideas through quickly, whether they worked or not. He relayed to me how industry, very quickly puts ideas through and sees if they’re going to work or not work and quickly commercialize them. He said medicine was slower; well obviously in healthcare, a lot more science needs to be done, but to some extent he was very right. Especially when it came to neurosurgery or surgical specialties where we’re thinking of new implants or new tools to help us do surgery, we were much slower. And as an academic health care center and a professor, physician working in one, our sciences tend to be slow.

But the other missing pieces was having, really engineering minds and people with commercial minds working together with physicians and surgeons to help them accelerate their idea, meaning to develop the engineering aspects of their conceptual ideas into prototyping devices and seeing if they would work. And basically, out in the real world, that’s called an accelerator or biotech accelerator, as you mentioned. But that is a new thing for an academic health care center. Now, a lot of large university centers all over the world – and I traveled all the way to Spain, to a couple of centers in the United States that tried this, but it sort of failed. Hundreds of millions of dollars were spent on developing this, but it didn’t have the flavor and did not succeed as well.

So, we thought we would try it differently at a very small level, rather than build a huge hundred-million-dollar building, to within the department of neurology, hire engineers with that kind of frame of mind of developing and commercializing products and working everyday with the surgeons and having them live here within the department, within the clinics, within the operating room. And that’s the beginning of ZIAN, it needed an infusion of dollars which the Zucker family -- finally, after he passed, Jerry Zucker passed -- and about a year later, his wife Anita donated money and we started ZIAN. It’s been a very successful thing having the engineers work hand in hand with the trainees, young faculty, and professors in neurosurgery and in neurology. We’ve been able to patent several ideas, many have been already commercialized, and what’s most satisfying is that once there was an idea, and now within three years we get to use that concept, that instrument in better care for our patients and everybody’s benefitted from it, especially the patients. That’s the background on ZIAN.

[00:05:37] Lynch-Reichert: Which is an incredible opportunity and you mentioned that other academic health centers have tried and failed but you guys decided to start with a very particular foci, if you will, so how would you explain your success?

[00:05:57] Patel: So, I think what makes things successful – I think you’re right, anytime you want to build something you ought to incubate that concept and the development of this accelerator didn’t mean we needed to serve 800 physicians at one go. I thought we would trial with a small group of people. The other reason why it succeeded is because ZIAN was not an isolated group of engineers just working on their own. Everyday and once a week, I met with ZIAN engineers and the inventor and pushed the processes through. You know, many times when you have R&D research labs and companies making instruments or implants, these companies are remote to where we work. Here in ZIAN, we made that as part of what we do in neurosurgery.

So, like I would have a research lab and meet my research group once a week, at least once a day, we did that with ZIAN. So we were able to drive the process and push both engineers and inventors to keep working on their concepts. And I think that’s very important. If you look at the foundation for research, which is the place where we file our disclosures at MUSC, once you file it, it’s a piece of paper with a signature sitting on a shelf somewhere. That doesn’t develop anything. You can say “yeah I’ve filed a patent”, but that doesn’t do anything. What ZIAN is is the engineer then takes that idea and makes a prototype. And two days later the surgeon meets with them and then every week, I come into the room, and we have a meeting. That’s where we look at each concept, each prototype and say “Where are we with this? How is it going? What’s the next step?” Look at the inventor – “You’re supposed to have done this? What do you think about this iteration? Why would this not work? What’s the animal test show?” etcetera, etcetera.

So, I think there needs to be a two-way street here. Engineers on their own can’t do anything, surgeons on their own. You’ve got to have a driving force, almost a frequent regular meeting that drives the research. Just like any research lab would have. So I think that’s what made ZIAN successful and engineers are supposed to come to the operating room where the surgeons are and surgeons are supposed to go to the engineering lab where the 3D prototype machine is and meet with each other. Engineers need to start thinking like surgeons and surgeons need to start thinking like engineers and when they work together, I think you can have a successful thing happen. I think that was very important.

ZIAN engineers are officed right inside the department, I was the only and still remain the only department in the College of Medicine at MUSC who has engineers, they actually have official appointments with us, but they work in ZIAN. So it was a little bit of an out of the box concept. When somebody says you can’t do it, that’s the key word for me. I can. I just need to be told I can’t do it and when somebody says I can’t do it, that’s when I know I definitely can. That’s what we did.

[00:09:27] Lynch-Reichert: That’s why I love our faculty, our research faculty, our clinical faculty working together to make that difference. It also distinguishes us from other health care institutions as an academic health center and I think you said it splendidly many a time, that this cross pollination of ideas and the dynamic nature of the research process just lends itself to that innovation and discovery. So, you’ve got a product, you got together with all of your colleagues. What is ZIAN’s timeline to market on a product?

[00:10:08] Patel: So the fastest we’re able to take something, it was a small needle like thing that we use for neurophysiology, was 18 months. And we licensed it and sold the first product in 18 months. That’s a dream come true; I mean we won’t see that kind of trophy in the near future. But, you know, we have other things that are being patented and licensed but waiting for the company we partnered with to further develop it. 18 months was the quickest. There are at least three things that have been already licensed that are about to hit the market in the next six months, of course the pandemic sort of slowed everything down out in the real world. It didn’t stop us. ZIAN continued meeting every week, even during the pandemic. Creativity and invention does not stop because of a virus.

[00:11:06] Lynch-Reichert: You got that right. Now I would like to pivot to the other side of our academic health center. A much slower process than a biotech accelerator, but no less important in life saving. I am speaking of the third leg of the tripartite mission of MUSC – the research that moves the needle forward for better understanding of disease, better treatment, and in the best cases, cures, and the reason why we do Science Never Sleeps podcasts. Dr. Russell “Chip” Norris is a professor in the Department of Regenerative Medicine and Cell Biology at MUSC. And if I may say, a renaissance man, an innovative scientist.

Joining him today at the microphone is Gensemer, a fourth-year doctoral student in his laboratory and lead researcher of an uncommon connective tissue disorder, called Ehlers-Danlos Syndrome or EDS. Chip and Cortney share a unique interest – Cortney has the EDS disease and Chip has relatives with similar concerns. Rounding out the team, Dr. Patel specializes in surgical treatment of the disease and has treated Cortney. So, let’s start with a basic understanding of EDS and what is its prevalence. Dr. Norris, would you provide the background?

[00:12:22] Chip Norris, PhD: Sure. Happy to be here. Ehlers-Danlos Syndrome are a group of connective tissue diseases. These diseases affect joints and ligaments and the specific type we’re studying is known as hypermobile Ehlers-Danlos Syndrome. It’s one of 14 different types of EDS and it’s by far the most common. The prevalence isn’t really well understood, its conservatively estimated at affecting 1 in 500 people but we believe it’s really far more common than 1 in 500. People with hEDS, as it’s called, have a number of problems in their joints as well as other areas of their body. Really the disease affects collagen and collagen can be viewed as the glue that keeps us together. So any organ or tissue that has collagen will have a defect and so patients have widespread chronic pain because of joint laxity. They dislocate their joints, they have GI problems, gastrointestinal problems, they have craniocervical instability and Chiari malformation and tethered cord which are neurological problems that Dr. Patel treats at MUSC. So, it really is a disease that affects many different organs and tissues and is chronic. It lasts the patients entire life and so we need to really get an understanding of what causes the disease and what can we develop to make treatments more relevant.

[00:14:27] Lynch-Reichert: I think one of the things that kind of astounds me is if you look at Cortney, one of the patients that suffers from EDS -- here is this vital, attractive woman that from the outside, who would know? Who would know the issues that she’s dealt with. So, I think it’s important for the public to know that this is not a disease that’s visible per say. The fact that you think there’s more than 1 in 500 suffering from this disease... what makes you think so?

[00:15:00] Norris: So the diagnosing of patients with EDS is a big problem. It’s not well understood by physicians so it’s hard to diagnose. It’s a clinical diagnosis and since it’s a multisystem disease, these patients have to see a lot of different types of doctors and these doctors – if you go in for chronic pain or you go in for a GI or cardiovascular problem, these physicians are not linking the dots together. They’re not really coordinating the different phenotypes into one syndromic disease. So we think it’s more than 1 in 500 because the physicians just aren’t making the connections between the different types of defects in these patients.

[00:15:55] Lynch-Reichert: And well, the question also comes up – is it a genetic disease? And if so, there’s no -- when you’re going for a physical or whatever and you present with some of these issues -- there’s no -- I mean, Cortney in your case did you say to somebody, “Oh by the way this runs in my family?” Because, if you wouldn’t mind telling your story, you didn’t really get diagnosed until very recently.

[00:16:24] Cortney Gensemer: Yeah, so I was diagnosed when I was 19 years old. I had signs of EDS my whole life, but it wasn’t until I had multiple major injuries in a row that someone finally connected those dots. It actually took me being diagnosed for my father and other people in my family to then get a diagnosis. One of the reasons too is that women are more severely affected than men, so in our patient registry right now, we have over 1500 patients from across the United States and roughly around 95% of our participants are women. In a lot of those families there are men who are affected as well but they probably would have no idea had a woman in their family who was more severely affected not been diagnosed.

[00:17:14] Lynch-Reichert: Why is that, why women more than men? Is that part of the question you’re trying to answer?

[00:17:20] Gensemer: Yeah, absolutely. So there are definitely hormonal influences on connective tissue and joint laxity and things like that, so we are in the process of investigating how hormones are playing a role in females being more severely affected.

[00:17:36] Norris: Yeah and getting back to the genetics question – it clearly has a genetic component. There is clear heritability that we know now for the disease and our registry, which has really been clinically revealing for these patients, is that 80% or so of the individuals in our registry report a family history. So you know that something has been passed down from generation to generation.

[00:18:09] Lynch-Reichert: So you could say it was serendipitous for Cortney to venture in your lab to discuss research options. You initially were focused on mitral valve prolapse but serendipity is sometimes the catalyst for discovery and you two have made some very promising discoveries relating to EDS. Even Miss America, Camille Schrier, wanted to meet you. Take us through the process that got you to this really promising next step – and I ask that because if you’re talking about genetics, what I hear all the time now is trying to find that biomarker related to a disease or something – so talk to us about what you’ve come across so far and how Miss America got engaged.

[00:18:51] Gensemer: Yeah, so to go back a little bit to sort of how we started this, I was a new PhD student at MUSC and during our first year, we do these lab rotations to sort of figure out what type of research we want to do and what research lab and mentor is a good fit for us. So, for the new students, Chip had come in and introduced himself and said “I’ve been at MUSC for a long time and if any of you need help navigating graduate school, I’m happy to help out.” I came in and had no idea what I wanted to do and so I was like ‘this guy seemed really nice so I’m going to talk to him and see if he has any advice on labs to look into or what might be a good fit for me’ and when I walked into his office I didn’t even know he studied mitral valve prolapse, so when he told me that, I shared that members of my family had mitral valve prolapse as part of Ehlers-Danlos Syndrome. And as a scientist, his first question was “What gene mutation does your family have?” And right away I was like “It’s the hypermobile type of EDS and they don’t know the genetic cause yet” and his eyes kind of lit up and he was like “Oh, do you want to try and find that?” I was like “Yeah, sure okay,” and as you can see, we’re here now, so we’ve been working on this for the past four years.

But it really started with an initial genetic discovery based on one family with hypermobile EDS. Where we identified a strong candidate gene for the disease, so we’ve been working on that for about the past year. We really wanted to make an impact on the EDS community outside of just what we were doing in the lab and to me as a patient, that’s always been really important to me. I know that patients go years without an accurate diagnosis, struggle to have doctors take their symptoms seriously and don’t really know what’s going on with themselves, so we wanted to make an impact on the EDS community from an outreach and advocacy and awareness side of things. And we got in touch with Camille Schrier, Miss America 2020, because she had been outspoken about her experience with having EDS herself, and hypermobile EDS specifically which is what we’ve been working on. So, we were really excited to talk to her – she’s actually in a science program in pharmacy school right now so she was so interested in the science we were doing. She was able to come to MUSC and spend time in the lab with us but also help us online through social media and through things even on the MUSC campus, to really spread awareness about EDS and how people are affected and help us with fundraising efforts to really help us expand our research and also reach for even bigger goals like the idea of developing a center for EDS at MUSC.

[00:21:36] Lynch-Reichert: Which is very exciting, and I think you’ll agree with me that an academic health center like ours, the only one in the state, is a prime location to make that happen. You’ve got your basic scientists, you’ve got your clinical scientists, you’ve got the hospital. It all comes together and great cross-disciplines. What do you think, Chip?

[00:21:58] Norris: I think we absolutely need to work on developing a center. The challenge with EDS patients is it’s a very complicated disease and oftentimes they’re not able to find appropriate care in their own city, so they have to travel. They have to travel to see orthopedists, they have to travel to see gastroenterologists, and these are travels that go across state lines. Because there is no real, designated center with a holistic approach of treating the disease where we can really treat all the different comorbidities and tissue problems with the disease. So developing a center here at MUSC would be lifechanging for patients with EDS. It would make MUSC a destination center for the hundreds of thousands of people in the US alone that have the disease. You pair the physician expertise -- which here we have a number of physicians who know what the disease is and how to treat it. So you pair that with a molecular diagnostics lab, a genetics lab, and then you can really provide groundbreaking discoveries as well as groundbreaking treatments that ultimately are going to be really beneficial for patients and patient care.

[00:23:41] Lynch-Reichert: You guys just had this one great breakout discovery – what’s your prognosis about how long it will take you to get to someplace where you really have something that can go to clinical trial?

[00:23:56] Norris: So that’s obviously a goal. Thera re a couple ways to approach the clinical trials one. The big problem with patients with EDS is diagnosing and having a diagnostic tool will change the lives of these people. Outside of the medical management of the disease, having a diagnostic tool, it takes on average 14 years for a patient with EDS to get diagnosed.

[00:24:23] Lynch-Reichert: Wow. That’s tragic really.

[00:24:26] Gensemer: That’s 14 years from the onset of symptoms. So it’s not that people are on average diagnosed at 14 years of age, that means that from the first time they really had a lot of problems and showed signs of the disease, it took 14 years until they were accurately diagnosed with hypermobile EDS. Not to mention that there might have been misdiagnoses or other things in that process that delayed their proper medical care too.

[00:24:51] Norris: Yeah, so it says 14 years -- during that 14-year period where these patients don’t know, and they engage in activities that may actually be very detrimental to their life. So, you know, it’s important to get diagnosed especially if you have someone in your family that has been diagnosed, the chances of having it are much higher. So having a diagnostic tool is really important. Our genetic discoveries I think are a first step in establishing a diagnostic tool. Putting a timeframe on it is always challenging and I don’t like to be held to timeframes [laughter]. But you know, certainly within the next few years is possible, if not sooner.

[00:25:50] Lynch-Reichert: Is there such a thing as – I’m just thinking of something – you know, how sometimes you can look online and you’re trying to figure out ‘I’ve got some problem’ and you go through a checklist. Have you guys come up with a checklist like ‘if you have this and this’, you know if you keep going through, and ‘if you said yes to this’, like one of those kind of maps, would that be a potential first step for people to say “Hey I need to look into this more”?

[00:26:23] Gensemer: Yeah, so currently for clinical diagnosis for hypermobile EDS, there is a checklist that was put out by the EDS Society in 2017. It is a good checklist and it’s helpful, but it could definitely be improved, and I know that there are clinicians out there working on ways to improve this, but we have also worked hard on our lab website to put together a list of resources for both patients and physicians. Even things like physicians who are interested in CME credits to increase their understanding of EDS. And then things for patients – lots of resources to things on how to accurately be evaluated for EDS, the diagnostic criteria, as well as links to our literature review that we published on the disease and even some additional things on like comorbidities that are associated with EDS for patients to reference.

[00:27:17] Lynch-Reichert: So, I want it to be clear with our audience that it started out at the bench in your basic science lab, Dr. Norris. You lucked out and got a great doctoral student who could be part of this really exciting discovery. You pulled in neurosurgeon Dr. Sunil Patel to help with the clinical aspect of things. This is what the audience needs to understand -- that sometimes it takes a long time, from the basic bench side of the house to the bedside, but that’s what we’re really good at here. Cortney, how does it feel for you personally to be at the forefront of what could potentially be the beginning of the end of the disease that has compromised your quality of life for some time?

[00:28:08] Gensemer: It’s really exciting because I think that being able to have a patient perspective in the lab – for me obviously the research means a lot – but it really also gives meaning to what we’re doing to other people in the lab too. I think in a lot of labs you’re studying a very specific protein in a disease, and it’s so withdrawn from the patient experience that you can often miss things that are really important. But I also recognize that I am, in terms of the spectrum of severity of EDS, I’m really more towards the middle and because of that I’m able to have this opportunity to do this and we also wanted to give that opportunity to other students.

So, I just wanted to mention the intern program we did in our lab over the summer. We actually had an internship program specifically for undergraduate and graduate students who also have hypermobile EDS. Who have an interest in research or medicine, or some aspect of clinical care and we had four students that were chosen, and we actually had a lot more applicants than we anticipated. We wanted to take three students and we had to take four because they were so awesome, and we had them in the lab working on various aspects of EDS.

Because what our big goal here with the internship program -- not only to have them contribute to the research but to go into their careers later having a really good understanding of the disease so that they could take that information and teach others in their programs and their hospitals and wherever they are later to kind of increase the number of people out there who understand what EDS is so hopefully we can kind of start at the bottom and improve patient care from that aspect as well.

[00:29:45] Lynch-Reichert: And that’s what it’s all about. And that’s why we’re here. And that’s why we do Science Never Sleeps podcast. This, dear listeners, is why science never sleeps at the Medical University of South Carolina. Long hours, hard work, peer review, frustrations and triumphs are all part of the research endeavor, which begins with the question “why?” and ends hopefully with a patient, family, community living a happy and healthy life.

Thank you to the Zucker family for their generous support of ZIAN, and Dr, Sunil Patel, Dr. Chip Norris, and especially doctoral students Gensemer and Allison Trouton for their generosity of time, their commitment to finding the answers, and for sharing this story.

I also want to thank our faithful listeners. This is our last podcast of 2021 and my last podcast as your host. I am retiring from the Medical University of South Carolina, however Science Never Sleeps will continue in the new year with more fascinating discussions. It has been a privilege to be by your side to discuss the biomedical health questions of the day, to raise your understanding of and interest in the people, processes, and science behind the research at MUSC.

Special and heartfelt thanks to the Medical University of South Carolina, the Office of the Vice President for Research under the guidance of Drs. Kathleen Brady and Lori McMahon. To our incredible and truly talented Director of Academic Media, Jonathan Coultas, and especially to our esteemed faculty whose work both at the bench and the bedside continue to fuel hope for the future. Because at MUSC, science never sleeps. Thank you so much for your support. Stay well.