Welcoming Our New CEO, Joshua Tarnoff March 6, 2018 by Lauren Eva NephCure Welcomes Joshua Tarnoff, Our New Chief Executive Officer The NephCure Board of Directors is thrilled to announce that Joshua M. Tarnoff has joined our team as Chief Executive Officer. Read the full press release here. Recently, we spoke with Josh to learn more about him and what he’s looking forward to in his new role. Read more about Josh and what’s on the horizon for NephCure in our full interview with him, below. NephCure: Could you lead us through some of the professional experiences that brought you to NephCure? Josh Tarnoff: From a professional perspective, I’ve been in the healthcare industry for over 30 years in various management roles. One of my passions in particular is in growing organizations: it’s not uncommon for me to be the first employee in an organization or new start-up and take it for a 5-year run or so to grow it. At AstraZeneca, I started up one group, and by the time I left, that unit was doing a billion and a half dollars in sales. At Complexa, it was pretty much the same, and they’re now on their way into a Phase II clinical trial. This also applies to civic organizations, where I started a co-ed youth group. So my experience, as well as what I enjoy, is in taking organizations to the next level. If he’s not at the office, you’ll probably find Josh outdoors—he loves backpacking, sailing, fishing, and scuba diving, to name just a few of his outdoor hobbies! NephCure: What is it about working for NephCure, a patient advocacy group, that interests you? Josh: It’s both personal and professional. On the personal side, I was bitten by a rattlesnake about 15 years ago, and I wound up with extreme kidney failure and interstitial nephritis. It was life-threatening. I had to take massive doses of steroids for a long time, and I now live with long-lasting side effects from those drugs. I have cataracts and metabolic conditions going on that will live with me for the rest of my life. So there’s a personal touch in recognizing that we need therapies for kidney disease that just don’t exist right now. And I know that in my experience with kidney disease, I’m one of the lucky ones. But I can relate very much when I hear patients talk about what they’re going through and there not being many options. From a professional perspective, NephCure is an organization that I’ve seen, from the industry side, really make a difference. NephCure is an organization that’s been around for a relatively short time—not like many of the large organizations that have been in existence for 50+ years—and in that short amount of time, has made a tremendous impact. Not many years ago, there were absolutely no alternatives to steroids for these diseases; we now we have the FDA collaborating with key opinion leaders, industry, patient advocacy groups like NephCure, and patients. Through this collaboration, we have been able to witness the modification of drug approval guidelines, which made it easier for companies to bring new therapies into late-stage research. At the end of the day, we now have a pipeline of drugs that are coming through that target FSGS and related nephropathies. Through its advocacy and being the ‘center of the wheel,’ this is an organization that’s really done something tangible: there are now new treatments on the horizon that didn’t exist before, largely because of NephCure. To join NephCure at this time is extremely exciting, because we’re doing things: these potential new treatments are real, patient outreach and connections are real, and clinician awareness is growing. Now it’s about taking the organization to the next level and making sure that effective treatments come to reality, making sure clinicians are trained in timely diagnosis so that patients get the care they need, making sure people are aware of what’s going on, and getting additional funding and organizations involved. This is the part where we deliver. NephCure: What do you see for the near future of NephCure? What do you see happening in the next five years? Josh: Today, awareness within the nephrology community is growing, but there is still some way to go. Earlier diagnosis and treatment are key. FSGS and other forms of Nephrotic Syndrome still go undiagnosed or misdiagnosed for long periods of time, in the early stages of the disease when the kidney is most vulnerable. We need to continue to drive awareness within the healthcare community to get ahead of the disease progression at this sensitive time. Another key is that there are now drugs that are about to be in Phase III of the clinical trial process and others at various stages clinical research—we have effectively moved beyond the basic research labs and into phases that hold promise not too far away. Meanwhile, there are thousands more patients developing this disease each year. It’s also a matter of getting the right care to these folks and expanding the patient registries that already exist. It’s building on some of the incredible work that’s already been done. In the next five years, we ought to have effective therapies available for patients that weren’t there before. All of this started with NephCure’s push nearly 20 years ago. In the near future, I see NephCure expanding its relationship with government agencies, clinical academia and the broader pharmaceutical industry. We will continue to have relationships with key opinion leaders so that we make sure there’s a seamlessness between a newly diagnosed patient and the future of their care. We will continue to bring all of these entities together and push the research and the care into the next level. Largely due in part to the work at NephCure, we now have a much better understanding of the pathophysiology of FSGS and related nephropathies. The role of the podocyte for instance was not as well appreciated for a long time. We have also seen data presented that directly associates levels of proteinuria with survival—something we long suspected but now have evidence to make that link. We know much better what needs to be done. Awareness and understanding has led to more involvement with people who develop clinical therapies. I think the organization has done a wonderful job of sponsoring grants for early phase research. As you know, it takes a new drug 15 years to get on the market. So NephCure planted those early phase research seeds long ago, and because of that, there are now new therapies being developed, and there are drugs that can be repurposed to treat these diseases. The good news is that more organizations are coming in. We have to match the progress that’s going on out there, step up our game, and make sure that the organization is even more involved with some of these key stakeholders. NephCure: Do you think we’re at a critical moment in terms of needing to act before some of these players perhaps lose interest? Or do you feel like it’s more of a waterfall effect, where new treatments are going to happen, and we want to be a part of this obviously to help move it forward, but the momentum is taking on a life of its own? Josh: If we let things will happen on their own, they will occur at a pace that’s really not acceptable. We have patients who are suffering and who are being debilitated, and the pace to get effective treatments in their hands can never be fast enough. It’s our job to be the center of the wheel, to be the catalyst and amplify the progress to be bigger and faster. You only get that by having real collaboration among the key stakeholders: patients, the FDA, researchers, physicians, and industry. NephCure raised awareness of these diseases from virtually nothing 20 years ago to much better awareness and understanding of the disease today. That led to basic research that has in turn evolved today to late-stage clinical research of new therapies. Things have significantly accelerated with the FDA’s addressing needed updates to drug approval guidelines, but we really have to stoke that fire, otherwise things will plod along at a slow pace. There’s a lot of opportunity for real breakthroughs in the next 1 to 5 years. There’s a lot of interest now that wasn’t there before, and we need to continue to play the leadership role and pull it all together. This is an organization where people have done an incredible job. I have the benefit of coming in to stand on their shoulders, which is really unique. We’ve got all these potentially impactful events on the horizon, and there’s a lot more attention than there was; there is a strong momentum now. I’m lucky to be able to come in at this point and work with everyone to make sure that we’re ready as this all takes off. We have to continue to be the catalyst for all of this, and make sure that the dialogue continues, that people continue to keep FSGS in the forefront, and manage it all. Because if not us, then who? I’m honored to be a part of this organization. It’s really humbling. This is something that I’ve always aspired to do. When people ask, “Where do you see yourself in ten years?”, I’ve always thought I would try to transfer some of the work that I’ve done into an organization that’s closer to the patient and more front-line. When you’re with NephCure, you’re at the center of the wheel. And NephCure has a great mission. All the different parts we talked about—they’re not going to come together on their own. For me personally it’s very rewarding, because I’ll be able to work closer with patients, physicians, and government. To be able to have the time and the resources to do that, and make more of an impact than I had previously, is personally incredibly rewarding. Join us in welcoming Josh to our community. In the coming months, he’s looking forward to meeting you at events, learning sessions, and fundraisers around the country. Feel free to leave a note to Josh in a comment below! As always, thank you for your support as we move into the next phase of our mission to get better treatments and a cure for FSGS and other diseases that cause Nephrotic Syndrome to our community. Together, we will find a cure.
NephCure Supported Research: Gary W. Liu February 1, 2018 by Lauren Eva Gary W. Liu was diagnosed with Minimal Change Disease as a child. Today, he is investigating new ways to deliver drugs directly to the kidney in the hopes of one day providing a cure for diseases that cause Nephrotic Syndrome. Gary W. Liu Gary Liu is a fifth-year graduate student and National Science Foundation Graduate Research Fellow in University of Washington Bioengineering Professor Dr. Suzie Pun’s lab and collaborator with University of Washington Nephrology chair and clinician Dr. Stuart Shankland. We spoke with him recently to learn more about his unique story and personal approach to his bioengineering work. NephCure: Can you tell us about your diagnosis and experience with kidney disease? Gary Liu: I was diagnosed with Minimal Change Disease (MCD) when I was five. I remember that I was really thirsty and kept drinking water, but none of it was coming out. One night, I was in so much pain that I couldn’t move. All the water I’d been drinking didn’t have anywhere to go but up and out, and I vomited. I was taken to the ER and put on the typical treatments—immunosuppressants and glucocorticoid steroids. As I was a kid, I was constantly told that I would get over this, because MCD is a disease that is supposed to resolve itself. But as I entered middle school and high school and when I started going into undergrad, the disease was always in the background. There were periods when I was in remission, in which I was otherwise healthy, but then I would have a disease flare whenever we had to increase the dosage. These drugs had a lot of side effects that were particularly difficult to deal with as a kid. They made you gain a lot of weight, and on the playground kids were not very nice. Over time, as I lived with the disease and experienced firsthand as a patient the limitations of the available treatments, I was curious as to why there were not more effective treatments and a definitive cure. In undergrad, I looked into the literature and observed that there were not “engineered” treatments for diseases like mine—glomerular kidney diseases. When I applied to graduate school, I realized that I wanted to learn ways to apply bio-engineering to kidney diseases. I wanted to then take that training and one day start my own lab to engineer new treatments that can hopefully cure kidney disease. I draw upon a lot of the emotions and feelings that I had as a patient to try to remind myself everyday why I go to work: so that people and patients like myself don’t have to go through what they’re currently going through with the disease. Gary working in the lab. NephCure: Could you describe, for a layperson, your current projects in this area? Liu: In glomerular kidney diseases, there are cells that are very important for kidney function called podocytes. When podocytes are healthy and functioning, they look like octopuses. They have these “feet” that form a zipper with their neighbor. This zipper is really important for how the kidney is able to filter the blood—you can imagine that together the zippers form a nice filter. In a lot of kidney diseases, these podocytes are injured, or they undergo what’s called “effacement,” where the foot processes retract. If you have effacement or if you have a podocyte that dies off, your kidneys are now more leaky. They start leaking what normally stays in your blood into your urine. If that podocyte death or injury continues, that leads to irreversible kidney scarring and eventual kidney failure. When we look at what the current clinical standard for treatment is—immunosuppressants, the anti-hypertensives—they do work for some forms of kidney disease, but they don’t address this fundamental problem of podocyte dysfunction or podocyte loss. One of the projects that we’re looking into is how we can take advantage of natural stem, or progenitor, cells in the kidney and then engineer them so that they can regenerate these podocytes that are lost. Image borrowed with permission from Gary Liu’s presentation, “From patient to researcher: Transforming kidney disease treatment” There’s been a lot of exciting findings in this area. The Romagnani group in Italy found that if you collect urine from kidney disease patients, you’ll see that they lose progenitor cells into their urine. They’ve shown that if you take these cells from kidney disease patients and then inject them into mice with kidney disease, these cells actually go into the mouse kidney and start regenerating new functional podocytes. If we can collect urine from people with kidney disease, grow these progenitor cells, and then inject them back into the patient, this could be a new way of treating patients with their own progenitor cells. What we’re trying to do is better engineer them so this can be a more effective clinical therapy. We’re looking at two different routes to go about this. One way is to graft nanoparticle “backpacks” onto the stem cells. One of the challenges whenever you inject cells into the body is that you lose a lot of them, because they have to be able to circulate for a long time; they have to be able to survive before they can actually get to the kidney. If we have nanoparticles that are loaded with the drugs, the cells could survive better. It’s kind of like these cells are hikers, and we’re giving them backpacks with food and a map so they know where they’re going. These drugs can enhance their proliferation and survival once they’re injected into the body. We think that these will be able to help these cells survive longer, so that they can go into the kidney and actually differentiate into functional podocytes. Image borrowed with permission from Gary Liu’s presentation, “From patient to researcher: Transforming kidney disease treatment” The other route we’re considering is a non-viral means of genetically engineering these cells. In viral genetic engineering, there’s always a risk of oncogenesis, or causing cancer, because viruses inset DNA randomly within the host DNA. If we can do this non-virally, we increase the safety profile so that the DNA does not necessarily insert randomly. We then provide a means of genetically editing these cells, which means that in patients with genetic causes of kidney disease, this might be a curative therapy for them. Through our work with nano-sized materials, we are beginning to understand that the charge (neutral, positive, or negative) of these materials influences where these materials go in the body. Our recent work has shown that materials that are very negative in charge home into the kidneys more than other organs. We’re very excited about this data, as this knowledge can lead to improved drug carriers that better deliver drugs to the kidneys for kidney disease, and hopefully improve the side effect profile of those drugs. Since receiving the grant, we’ve been able to make great progress isolating and growing renal progenitors from patients’ urine, and in initial animal experiments, these cells seem to decrease proteinuria and regenerate lost podocytes. We’re excited about these preliminary data, and are continuing with our “backpack” formulations. NephCure: You were able to receive funding for this project in a very particular way. Could you describe the grant you received and how it’s different? Liu: I received this grant through the Department of Defense’s Peer Reviewed Medical Research Program. Typically, for this kind of work we would have applied for funding through the National Institutes of Health (NIH). But we didn’t have that option because the National Institute of Diabetes and Digestive and Kidney Diseases (which funds kidney research as part of the NIH) didn’t have a way to fund early-stage projects without significant established preliminary data. We needed a funding mechanism for this project that encouraged high risk, high potential impact work. The Department of Defense route for funding had not been done before, because kidney diseases such as FSGS were not listed as an option to study until 2016. [Editor’s note: the Department of Defense Peer Reviewed Medical Research Program designates a list of conditions each year that researchers can select from to apply for funding to study. NephCure volunteer advocates have so far successfully gotten FSGS on the list of designated diseases each year since 2016.] NephCure did a lot of great advocacy work on Capitol Hill to get FSGS on the list as one of the diseases that researchers can receive grants to study. Because of NephCure’s hard work with the Department of Defense, we were able to get these new and exciting ideas funded. The Department of Defense grant allows us to try to generate the preliminary data that may enable us to get more grants, or even perhaps entice biotech companies to get on board. We are incredibly grateful for NephCure’s great advocacy work. Through this route, our lab was able to secure much-needed research funds to support our work. Thank you to all of the patients, doctors, and activists who made the work I’m doing possible.
Spotlight on Lauren Lee, National Director of Research and Engagement February 1, 2018 by Lauren Eva NephCure Open Access: Spotlight On Lauren Lee, National Director of Research and Engagement In January of this year, we celebrated our National Director of Research and Engagement, Lauren Lee, and her five-year anniversary of serving the patient community at NephCure. During her tenure, Lauren has been a tireless advocate for the cause, with a sharp eye for innovation and new possibilities. Traveling all over the country in her various roles with NephCure, she has never forgotten a face, story, or name. NephCure’s growth and maturity as an organization would simply not have been possible without her contributions, and it is an honor to work alongside her. To commemorate her five-year anniversary, we’d like to give you a closer look at who Lauren is and how she approaches her role at NephCure. Below, we share our recent chat. NephCure: Five years is a long time, and a lot has happened since you’ve been at NephCure! But I wanted to start with a brief overview of what brought you here. Were there other positions that helped lead you to this point? Lauren (left) with NephCure staff member Chelsey Fix. Lauren Lee: I’ve spent most of my career working in various nonprofit settings. The most related to NephCure prior to coming here was working at the University of Pennsylvania Health System, where I did fundraising and development for various departments, including medical research fundraising. After taking some time off to raise kids, I started working for a small cancer-based pharmaceutical start-up. They were looking to develop an immunotherapeutic medicine for acute myeloid leukemia. It was there when I was developing investor fundraising materials, which were more technical but were also centered around telling a compelling story about the patients and the disease, that I started to think about how can you make a case for drug discovery or disease research by putting patients at the center of it all. When that particular company started running out of money, I knew that I wanted to keep working, and I applied to various nonprofits because that’s where I feel most at home. Happily, I ended up at NephCure. NephCure: What’s your favorite thing about NephCure today? Lee: My favorite thing about NephCure is that we’ve taken a mission that is often hard to articulate and get people excited about—funding medical research around two rare diseases—and turned it into a meaningful movement and message. The landscape around NephCure has changed significantly just in the five years that I’ve been here. When I first started, we were purely focused on giving out grants and raising money to fund young investigators and various consortia, which felt very lab-oriented. While that work was very important and jump-started a lot of the breakthroughs and advancements that we are now able to see and use today, we were less focused on engaging the patients in the research and in our day-to-day work. One of the things that’s happened, amazingly, in such a short amount of time, is that we’ve taken the mission and articulated it to our patients in a way that helps them understand how vital they are to our goal of finding better treatments and a cure for these diseases. Our patient community now really understands that they’re very much a part of this mission. None of the research that’s happened, whether it be in labs or in drug discovery, or anywhere, can happen without their involvement and enthusiasm and support. NephCure: What do you like about your current position as National Director of Research and Engagement? Lee: I like that it marries understanding the unique experience of living with Nephrotic Syndrome and creating programming for patients with what was once a sort of sterile mission to fund research. Now we have a story to tell around it, because our early investments in research have opened up so much opportunity. We’re seeing that the results of those investments have stirred the pot in getting researchers, biotech companies, pharmaceutical companies, and the government to take notice and start investing in and thinking about Nephrotic Syndrome. In addition, we now have a more mobilized patient community that can get involved in the process. Lauren (left) representing NephCure and presenting a Nephrotic Syndrome symposium in Boston, MA. And it’s fun! It’s been a wonderfully serendipitous opportunity, at least for me personally, to be creative. Early on, we didn’t think about programming specific to patients necessarily in a creative way—the bulk of our patient education was basic Nephrotic Syndrome 101 information. Today, we also offer programming that helps educate and engage patients around their mental and emotional health. We’ve recognized that not only is Nephrotic Syndrome rare, it’s chronic, and we’re trying more and more to understand what that means for our patients. We’re constantly thinking about how we can provide resources that will help them better deal with their disease and be equipped to feel better, to have more meaningful conversations with their doctor, and to be more proactive in their health. NKI: Which leads into my next question—what are your plans and your department’s plans for 2018? Lee: Lately, there’s been a lot of attention focused on potential therapies and treatment options for Nephrotic Syndrome, which is wonderful. We’ve had the opportunity to be part of these discussions with pharmaceutical companies and smaller biotech companies, and we are now viewed as partners to their different plans for developing these new therapies. A lot of the focus in 2018 is going to be on helping connect our patients to clinical trial opportunities that they can participate in, while also continuing to educate them on what it means to participate in research. I believe that there are research opportunities available for everyone, no matter who you are, or what stage you’re at in your disease journey. Perhaps you’re not eligible for a particular clinical trial, but we have the NephCure Kidney Network Patient Reported Information Registry that people can participate in by completing a survey about their health journey. There are also a number of longitudinal health studies, like CureGN and NEPTUNE, that we can direct people to. The more we can get people educated and engaged in these different research opportunities, whether they be clinical trials or some of these longitudinal and observational studies, the better off everyone will be, because we’ll be able to continue to answer important questions about Nephrotic Syndrome that will lead us directly to better treatments and a cure. NKI: Is there a patient story or experience that reminds you why we do what we do every day? Lee: Certainly—connecting with patients one-on-one, which I wish I could do more of. Anytime I sit down with a patient and listen to their concerns and struggles over being diagnosed, or having a child or a spouse diagnosed with Nephrotic Syndrome, I’m deeply touched. Lauren (bottom row, second from right) during a patient panel in 2017. One of the things that’s been exciting and heartwarming for me are the patient panels that we’ve been presenting over the past couple of years. The panels bring patients in front of an audience of clinicians, fellows, residents, pharmaceutical representatives, and researchers, and we allow that audience to hear straight from the patients about the emotional struggles and other aspects of living with the disease that they perhaps never thought about while treating them during a 20-minute appointment. Bringing the patient story alive for this audience and creating opportunities for “Aha!” moments helps the doctor or health care professional go back to the clinic and do a better job of communicating with the patient. It helps them understand what a Nephrotic Syndrome diagnosis means to a family—it’s not just impacting the patient, but everyone around them. NephCure continues to find ways to connect patients with these audiences, and that’s made all the difference—both for the patient and for the healthcare professional or pharmaceutical representative. Taking their interaction out of the doctor’s office and putting it in a Friday forum where you’ve got a large group of people spending a day learning and connecting benefits everybody, all around. NKI: I know you are incredibly dedicated to NephCure, and you spend a good amount of time traveling for the cause. But what are you doing when you’re not working for NephCure? Lee: Being a mom to two teenagers! And juggling activities, heavy homework loads, good days and bad days at school, and helping to guide them. Personally, I’ve also been doing a lot of hiking, and I do a ton of yoga. But spending time with the family is what I do most. That’s my priority. NKI: Is there anything you’d like to add? Lee: What I’m really proud of NephCure for, and what I’ve seen come to fruition—and I see it play out everyday here—is the fact that we are the anchor for this disease. We have convened people from all over. All of that work in trying to know what’s happening in all of the different realms, with physicians and with the pharmaceutical industry, the FDA and the NIH; it’s now really playing out in that those entities look to NephCure to take the lead, to facilitate connections, and to be the hub for all Nephrotic Syndrome research and activity. To be the organization of record. I think that’s important for our constituents to know. My inbox is filled everyday with messages from all of these different entities seeking us out. We’re thrilled to be celebrating this anniversary with Lauren and look forward to watching her continue to make strides on behalf of patients and families with Nephrotic Syndrome around the world. If you’d like to speak with Lauren, please feel free to leave a comment below, or send her an email at LLee@NephCure.org. Congratulations on a fantastic five years, Lauren!
Why I Do What I Do: Spotlight on Tyler Wellman, Patient Family Supporter December 4, 2017 by Lauren Eva Tyler is the younger brother to Will, who was diagnosed with Minimal Change Disease at 25 years old. His disease quickly progressed to FSGS and then kidney failure. Will received a kidney from his mother, but the FSGS began attacking his new kidney soon after transplant. We sat down with Tyler to hear about his recollections of that time and how Will’s experience with kidney disease changed his outlook and influenced his life decisions. NKI: How old were you when Will first started having health issues due to his kidneys? (L-R) Brothers Will, Tyler, and Grant at the 2015 Tampa Pig Jig. Tyler: I think that was spring of my sophomore year of college; I would have been 20 or 21. I can vividly remember the day that Will started feeling rough. Will, my other brother Grant, and my cousin and I went to go see my grandma, and Will was already feeling pretty bad. We went into a Publix supermarket on our way, and Publix has these huge scales that you can weigh yourself on. We were walking out and all weighed ourselves, and Will was 15 lbs. overweight. He got on it and said, “What the heck is going on? Will you guys get on this and see if your weight is accurate?” We all got on it and said, “Yeah, it’s normal for me…” He said, “I’ve gained 15 lbs. That’s so weird.” And he just felt terrible. When we were at my grandma’s, he took a nap pretty much the whole time we were there. After that, a few doctors’ appointments later, he finally got diagnosed with Minimal Change Disease. It was almost a full year before they did a second biopsy and he got diagnosed with FSGS. NKI: When did you realize how serious it was going to be? Tyler: When he first got diagnosed, it was kind of well-controlled, and we had the understanding that MCD goes into remission with steroids. I had gone to Indonesia for two months that first summer that he was diagnosed with MCD, and he wasn’t really that sick at that time. But by the time I came back, he was starting to retain a lot of water weight. The steroids weren’t doing what they usually do, he was still putting on a lot of water weight, and it was hard for them to keep it off. I can vividly remember how puffy he was with all the edema. When they couldn’t figure out how to get it under control, it was really scary. He would just lay in bed all day, because if he stood up, all the water weight would go down to his legs. He had to lay flat. It got so bad that at one point he had stretch marks, and there was fluid coming out of the stretch marks because he had so much fluid. He was kind of kept prisoner by that. He just laid in bed all day. We felt so helpless because there was nothing we could do for him, and everything the doctors were trying wasn’t working. It was really frustrating and sad to see somebody you love suffering like that. NKI: Were you guys close growing up? What kind of impact did this have on you as a family? Christmas with the Wellman brothers Tyler: We’d always been really close; we were really close growing up. Both of my brothers and I would hang out and do a lot of stuff together. I had gotten really active with my faith and my religious life when I was in college, and at that time Will was in Kentucky in graduate school—this was before he got sick—and he was kind of trying to figure that stuff out too. So we got even closer talking about it. Then after he got sick, he became even more interested in trying to figure things out and make sense of his suffering. Having those kinds of conversations definitely brought us even closer together. NKI: It seems like both your and Will’s later life decisions were in some ways influenced by Will’s experience with kidney disease. Could you talk a little bit about your decision to become a doctor? Tyler: When I graduated from college, I went to Micronesia and taught high school for two years. My plan was to maybe go to graduate school or to seminary when I got back. But then, after I was there for a little bit, I realized that I didn’t want to go to seminary. I wanted to do something more hands on, I wanted to have a skill set that I could offer a community. At the time, I was teaching biology in Micronesia and getting updates with what was going on with Will and the treatments that they were trying. I was trying to understand why Will was taking chemotherapy drugs, why they couldn’t figure out what was wrong with his kidneys, and why this was all happening so fast. I remember reading on Wikipedia all the time about these things and trying to understand it. This was all while I was teaching biology and getting really interested in the biological sciences. That got me into thinking about medicine. Then, after being in Micronesia for about a year, Will had his kidneys removed because he was in kidney failure. I went home in December of my second year there for a few weeks for Will’s kidney transplant. I pretty much stayed in the hospital the whole time I was home because Will was there. I would go home to sleep and shower and then go hang out with him all day in the hospital. Tyler and Will with Chris Whitney (center), a close family friend, at NephCure’s Washington, DC Advocacy Day this year. When I was there with him, it all started to click for me: that medicine would be a good fit for everything that I was interested in. Seeing Will’s interactions with the doctors and seeing how much of it for Will was more than just a medical thing, that there was also this spiritual and psychiatric component of dealing with illness—that really appealed to me. After that, I was sure I wanted to go into medicine, and from there the idea of medical school took on a clearer form. NKI: What was your reaction when you found out that the transplant wasn’t going to end up working out for Will? Tyler: That’s another vivid memory. After Will had the transplant and the surgery was done, he had to go to the ICU because his blood pressure was out of whack and hard to control. My cousin and my brother and I were hanging out in the ICU a lot. I remember being in there when they told us that there was protein in his urine, which was a sign that the disease was already starting to damage his new kidney. And you could see on Will’s face, it was just the worst news you could imagine. It was heartbreaking. My mom was still in the hospital recovering from the surgery when Will found out that the surgery was not… that nothing would come of it. He hadn’t even had the kidney for a full month before they took it out. He had had all these ideas in his head about what life after transplant was going to be like. You could see on his face, all of that had just gotten taken away from him. There was so much buildup going into it, for all of us, all of these expectations—that Will was going to get this transplant and everything was going to be better, that he was going to be able to travel all the time. My mom was a perfect match. Everything seemed so good going into it. Then just like that, it was all taken away. It was pretty devastating. After that, I had to go back to Micronesia. When I was back there, Will had his third surgery where they took out my mom’s kidney. NKI: I know Will has mentioned that he wouldn’t want another transplant until there’s a cure. Tyler: Yeah, we talk about that every now and then, because having two brothers, Grant and I obviously wouldn’t think twice about giving our kidneys to him. But I think it was just so emotionally traumatic for him to go through that, that the thought of doing it again is overwhelming. He doesn’t want to ever have to experience that again. NKI: When you think about the future, your hopes for yourself or your hopes for Will, is there anything in particular you focus on? Tyler: I think about Will’s capacity to understand human suffering and to connect with it and make sense of it. I think about his ability to retain faith and hope, while also being able to help people get through their own suffering and help them make sense of it, too… I think he has the capacity to do that where few other people do, because of what he’s been through. His faith has become so important to him. Most people that have changed the world or have gone on to do huge things, most of them either grew up under oppression or they had a traumatic experience when they were young that was a turning point and filled them with a sense of purpose and drive. I think that’s the redeeming part of all the suffering that Will’s dealt with. It’s given him this very clear sense of purpose and knowledge of what he wants to do with his life and how he wants to contribute to the world, in a way that other people who haven’t had to go through a negative and dark experience like that don’t necessarily have. I think it’s impacted me in the same way, just obviously to a much lesser degree than it has him. But I think our capacity to confront suffering head-on and to try and make sense of it has been very much impacted by that. It definitely plays into how I envision myself taking care of patients. So much of my own personal drive and sense of mission and purpose comes from the conviction that Will has of, to use religious language, of redeeming suffering. Of taking this negative thing and redeeming it to make it positive and to bring something productive out of it. I think that’s his whole understanding of suffering: that it’s not meaningless, and it’s not all negative. There’s so much good that can come out of it. It puts you in touch with other people in a way that life without suffering might not necessarily do. (L-R) Will, Grant, and Tyler and two of the newest members of their family at the 2017 Tampa Pig Jig. We were delighted to sit down with Tyler and so moved by his thoughts and memories of his brother’s diagnosis, transplant, and continuing ordeal with chronic kidney disease. We’re so grateful to have such a committed family be part of our NephCure community. You can meet Will, his family, and a community of NephCure supporters at the Tampa Pig Jig, which is held yearly in late October. Check back at the Tampa Pig Jig website to stay updated on the list of performers, schedule, and tickets.
Genetic Research into FSGS and Nephrotic Syndrome: an Update from the Pollak Lab December 3, 2017 by Kylie Karley An Update from the Pollak Lab By Andrea Knob We first checked in with the Pollak Lab and Andrea Knob—a genetic counselor and clinical research coordinator—about a year ago. Below is an update of their work, which receives funding from NephCure to study genetic causes of kidney diseases like FSGS and Nephrotic Syndrome. Patients and family members affected by FSGS and Nephrotic Syndrome are invited to participate in the Pollak Lab’s research. Please contact Andrea for more information. Andrea: As the holiday season approaches, we want to express our gratitude for the support of all of our patients and families, nephrology providers, and support networks including NephCure in the challenge to fight kidney disease. In the Pollak lab, we are working hard to identify and understand the genetic factors that may be contributing to the cause of kidney diseases such as FSGS (focal segmental glomerulosclerosis), Nephrotic Syndrome, unexplained proteinuria, and unexplained kidney failure in individuals and in families. We hope that by learning more about what causes these conditions, we can eventually help scientists discover better treatments with less side effects in the future. Researchers in the Pollak Lab Technology has been significantly improving over the years, and so has access to these technologies. We are able to look at genes and different variations of genes and study them in ways that were unimaginable decades ago. Genes (which we can think of as the “words” within DNA) are the instructions for the body to carry out its functions and give rise to traits. We look at genes related to the kidney in order to see if the instructions are what we expect or if there is variation. From there, we want to know whether a genetic variant is a normal part of the diversity from person to person or whether the genetic variant might be giving incorrect instructions for the kidney to function as it should. The Pollak Lab is looking for patients and healthy family members to participate in their ongoing study. You can participate from anywhere in the world! Here at the Pollak lab, we have identified genetic variants (mutations) that we know are associated with kidney diseases such as FSGS, Nephrotic Syndrome, and related conditions. We have done a lot of work with genes such as ACTN4, NPHS2, TRPC6, INF2, and APOL1, for example. We want to know more about these genes and how they work, but we also think that there are other genetic mutations to be discovered. Current genetic technologies allow us to study the actual genes, but we know that the stories from patients and families experiencing kidney disease is truly at the heart of the answers that we are seeking. If someone has a particular gene variant, what does that mean for that person? What are their exact symptoms? Do other people with the same gene variant have similar symptoms? What treatments have worked or have not worked? What additional factors (genetic, environmental, lifestyle) may be accounting for the differences from person to person and/or family to family? To answer those questions, we have to rely on the generous contributions of time, information, and personal stories from patients, families, and providers which helps us to understand kidney disease in new ways and helps us to develop new ideas and strategies aimed at prevention, diagnosis, and treatment. We are truly indebted to all who have participated in our research this year and in the past, for without your generosity, we would not be able to do the work we do. Andrea Knob—Genetic Counselor and Study Coordinator for Dr. Pollak’s study We also invite anyone to participate in our ongoing research, and we hope to team up with providers who care for individuals and/or families with FSGS, Nephrotic Syndrome, unexplained proteinuria, and/or kidney failure. We hope to continue our collaborative efforts and reach out to communities nationwide. We invite you to contact us at any time whether you are a patient, family member, or friend looking to learn more about our research, a previous research participant following up with updated medical, family history, and/or contact information, or a nephrology provider interested in referring a patient(s) and/or collaborating. Our study is very simple and can be completed from home. To learn more about us, you can contact us by phone at 617-667-0467, by email at aknob@bidmc.harvard.edu, or visit our website by clicking here.
NephCure Funded Research: Dr. Anant Madabhushi December 2, 2017 by Lauren Eva Dr. Anant Madabhushi is developing deep-learning software that could predict how diseases develop. In October, NephCure awarded Dr. Anant Madabhushi a NEPTUNE Ancillary Studies Grant for his work on computational imaging of kidney pathology slides. The Nephrotic Syndrome Study Network, or NEPTUNE, is a long-term observational study that has gathered health data and biological samples from close to 2,000 glomerular disease patients nationwide. Researchers can apply for grants to conduct research on this de-identified patient data. Besides having helped fund the creation of NEPTUNE, NephCure also now helps provide the funding that make a number of the ancillary studies possible. We recently spoke with Dr. Madabhushi to learn more about what he and his team will use the NEPTUNE data to study, and how he sees his work contributing to the future of precision medicine in the kidney field. NKI: Could you give us a brief synopsis of your work and what you’ll be using this award to study? Dr. Anant Madabhushi Dr. Madabhushi: Over the last 12-13 years, my group has been developing the technology and algorithms for analysis and computational characterization of tissue images. When someone gets a biopsy, their tissue slide has historically been read by a pathologist. But now with improved technology, we can scan these slides and create digital images. We can then start to train a computer to create a predictive model that is able to look at the digital images and identify patterns. Doing this could tell us about disease presence and aggressiveness and potentially about response to therapies, which is a big deal. Being able to use a computer to figure out, from a routinely acquired tissue slide alone, if there are patterns which may tell us which patients may or may not respond to a particular therapy is of immense value to a clinician. It allows for potentially better therapeutic management for the patient, potentially obviating the need for more aggressive therapies in patients who may not receive added benefit from them. So that’s been a large part of our work over the last 12 years. Most of our work has been focused in the cancer domain. I’m really excited about the NephCure award because it represents our first foray into the non-oncology space: we’re looking at kidney disease, which is somewhat novel to me. The project that we are pursuing with the NephCure award is to develop a set of tools and algorithms—software—that will start to analyze tissue images of kidney biopsies. With these tools, the computer has the potential to start to recognize patterns of aggressive disease. The ability to do that in the context of kidney disease is huge, because there’s still so much that we don’t know about kidney disease. We still don’t know so many things about response to therapy and outcome and prognosis in the kidney disease space. The long-term vision is that these tools will allow a clinician to be able to prognosticate, based on kidney biopsies, how a patient is going to do and what treatment might be appropriate for them. I need to qualify that we have one year. So the question is: what are we going to be able to do in one year, and how does that set the stage for the long-term vision and realization of the bigger picture of kidney precision medicine? The goal of this specific project is to develop a set of tools that will allow end-users, that is, nephrologists, pathologists, to use this software to create very deeply annotated mark-ups and portraits of the different structures in kidney pathology images. For instance, in kidney pathology images, we know there are different individual substructures, like glomeruli, proximal tubules, capillaries, and so on. The goal is to train the computer so that it can go in and start to identify all of these structures on its own. Once we’ve created a deeply annotated data set of images with all these structures identified, now one can start to ask specific hypotheses. For instance, once the computer has identified where all the glomeruli are, can I figure out whether there is an association with treatment response or recurrence of disease, just based on the number or location of glomeruli? So what we have is essentially a sort of a pattern-detection pilot project. Hopefully by the end of it, we’ll have these patterns mapped out by the computer, and then the nephrology and nephropathology communities can start to look at those patterns and say yes, these patterns seem to be important in transplant rejection, these patterns seem to be critical in chronic kidney disease or nephrotic syndrome. The goal is to create the enabling technology that allows clinicians and pathologists to go in and start asking those prognostic and predictive questions. NKI: Is this software that your team is developing something that, down the line, will get smarter with more data? Dr. Madabhushi: That’s absolutely right: the more you give it, the smarter it becomes. The problem is, it’s not just about giving it any data, you have to give specific data to the computer. In other words, if you want the computer to recognize what a glomerulus and a capillary are, you have to have an expert, a pathologist, sit down and map out these specific structures and then feed the image to the computer. The computer then looks at a large number of these and starts to learn and recognize these structures and then starts to provide the output. Let’s think about that for a second. Who are the people that are going to provide these annotations? They would be expert pathologists, nephrologists, and nephropathologists. These are not people with a lot of time. I’ll give you an example: we published a paper in Nature Scientific Reports looking at how to train a computer to recognize patterns of invasive breast cancer on tissue slide images. That work took four years, because we had 600 slides. On each of the 600 slides, we had to have a pathologist sit down and manually mark up where the cancer was. Those annotated slides were then used to train the computer. A lot of these algorithms are very dependent, not just on images and data, but on manual annotations of the data to become better and better. The pathologists and clinicians who are going to be able to do these annotations just don’t have the time. They don’t have the bandwidth to be able to sit and spend hours doing the markups and the annotation. What is the alternative? You need to be able to make the computer quick and efficient in the way it learns. One of the critical attributes of what we’re developing is a very lightweight version of this learning infrastructure. In other words, what if we could train the computer with just four or five examples? If you could, in 20-25 seconds, mark up what you want the computer to find on four or five slides, and then the computer rapidly uses just those four or five examples to create a network and a prediction and give you the results. An example of the way a computer can use deep learning, aided by manual annotations from a pathologist, to learn to identify the substructures of the kidney. Now, because the computer learned with just four or five examples, it’s probably not going to do a great job. But that’s okay, because what the end-user can now do is edit the results from the computer. Let’s say the computer found the majority of the glomeruli, if that’s what we’re going after, but it missed a few. Now the user can go in and say, “I see that the computer missed it here and here, so I will mark those up. I also see that in these few places, it seemed to identify something as a glomerulus when it wasn’t. So I will erase that because that result isn’t right.” So now with another 20-30 seconds of interaction, we’ve cleaned up the results from the computer. The computer then takes that cleaned up result and re-learns. What we’ve done is created a very efficient way for the computer to learn that is not taxing on the end-user. The initial result is not great, but with a few iterations back and forth, the computer can very quickly start to become very efficient and accurate. The other advantage of this model is that it makes it very generalizable. I won’t need to spend three or four years creating a dedicated glomerulus detector. In one day, I could have the software learn what a glomerulus looks like. This is a big deal, because what would have previously taken years, we can maybe do in a few weeks. That is really what is exciting about this. The computer is able to do the bulk of its own self-learning: We’re teaching the computer to be more effective in learning rapidly. NKI: You mentioned that you hadn’t really worked with the kidney before. How did you get involved with kidney pathology and get connected with NEPTUNE? Dr. Madabhushi: Three people: Laura Barisoni, John Sedor, and Michael Feldman. They got me into thinking about kidney pathology. Michael Feldman is a pathologist at the University of Pennsylvania. I’ve been working with him for a long time on a number of different cancers. He called me up one day and said, “We’ve got to start thinking about the kidney.” Before I knew it, I was connected to Laura Barisoni, who is one of the world’s leading nephropathologists at the University of Miami. And then, Dr. John Sedor, a nephrologist literally down the road at the Cleveland Clinic who I had not met before, stopped by my office one afternoon, and we started talking about the kidney and kidney pathology. So this conversation started about a year ago. It’s actually quite unbelievable. I met John and we started to brainstorm about opportunities in the kidney space. This work is the culmination of those conversations and the frequent meetings that we have. It’s been their persistence, resilience and passion that got me excited about kidney pathology. I’d been very happy working in the oncology space. This was them appreciating the utility of the tools that we’ve been developing in the oncology space and realizing that these tools could be transformative in the kidney pathology space. I really credit these three folks for bringing me over to the kidney side of things. I will say, this award is a real shot in the arm. It really energizes us. We’ve been doing this work off and on using cobbled resources. Andrew Janowczyk, Yu Zhou, and Jeff Nirschl from my group have done an outstanding job in creating the initial software infrastructure to get us where we are currently. Now, given the fact that we have this award, it really allows us to increase the tempo and rev things up. We can use this as a basis to launch potentially even bigger projects and create a bigger operation in the kidney pathology space. We had a great time chatting with Dr. Madabhushi about his work and are very much looking forward to seeing his team’s advances in kidney pathology imaging. Stay tuned to www.NephCure.org for updates on their research and other news from the field. Dr. Anant Madabhushi is the F. Alex Nason Professor II of Biomedical Engineering and the Director of the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University.
NephCure Funded Research: Dr. Michelle Denburg October 3, 2017 by Lauren Eva Dr. Denburg is focused on improving outcomes for pediatric Nephrotic Syndrome patients. In 2012, NephCure and the ASN Foundation awarded Dr. Michelle Denburg, a pediatric nephrologist at the Children’s Hospital of Philadelphia, a research grant to study vitamin D deficiency in the Nephrotic patient. Dr. Denburg is also a Co-Principal Investigator of the NephCure Kidney Network, a patient-reported outcomes registry for individuals with primary Nephrotic Syndrome diseases. We were thrilled to speak with her recently to learn more about her work and the impact that the NephCure-ASN grant has had on her research. Dr. Michelle Denburg NKI: In 2012 you received the NephCure-ASN award for your research on vitamin D deficiency in the nephrotic patient. Can you tell us a little bit about your work that NephCure has helped fund? Dr. Michelle Denburg: There are two studies that were related. One was an ancillary study to NEPTUNE, where we analyzed NEPTUNE baseline samples, measuring vitamin D metabolites and their hormonal regulators. We were looking at the relationships between what we already know in terms of Chronic Kidney Disease (CKD) and vitamin D, but specifically in terms of proteinuric glomerular diseases: the impact of proteinuria and relating some of the abnormalities of vitamin D metabolism to biopsy data and gene expression from the biopsies. The other study is a trial of vitamin D supplementation in patients with Focal Segmental Glomerulosclerosis (FSGS) and other glomerular diseases with persistent proteinuria—basically, treatment resistant patients. [editor’s note: The Nephrotic Syndrome Study Network, or NEPTUNE, is a long-term observational study that was formed to help understand the biology behind Nephrotic Syndrome. NEPTUNE has gathered health data and biological samples from close to 2,000 glomerular disease patients nationwide. Researchers can apply for grants, called “ancillary studies,” to conduct research on this de-identified patient data. Besides having helped fund the creation of NEPTUNE, NephCure also now helps provide the funding that make a number of the ancillary studies possible.] NKI: I know this work has not yet been published, but is there anything from those studies that you can share with us at this time? Dr. Denburg: There are some important things that we are going to be able to demonstrate and report. It’s fairly novel that we have measured vitamin D levels in the blood as well as the expression of vitamin D related genes in the kidney of people with glomerular disease. A lot of what we know about vitamin D metabolism comes from animal models. The fact that we have the NEPTUNE patients’ biopsy data and can relate the gene expression of these enzymes that are involved in vitamin D metabolism to their serum levels—this is highly novel from the research side. From the patient and clinician side, this is the largest study of vitamin D related mineral metabolism in a glomerular cohort. The prior literature is small case studies—this study included several hundred people. NKI: Do you think this work will change how patients are treated in their doctors’ offices? Dr. Denburg: I can’t comment too much on the results of these studies which have not been published yet, but the findings could have important clinical implications. I think the nephrology community may need to consider updating our guidelines on vitamin D replacement in nephrotic patients. Our current guidelines are based on CKD in general. In other words, there is no guideline for patients with glomerular diseases who may have normal kidney function but a lot of proteinuria, or patients who have glomerular disease and CKD. And we know that patients with glomerular disease in particular have several obstacles to bone health. One of my motivations behind this project is my interest in what we can modify to improve bone health in children and adolescents. Many of our patients are being exposed to a lot of steroids over time, and this is over the same period of time that they’re accruing the vast majority of their skeletal mass: about 90% of the skeleton is laid down before age 18. I’m interested in learning what we can do to modify and improve bone health in the face of therapies and illnesses we can’t avoid—that is, until we find a cure. NKI: How do we separate the way steroid use affects bone health for glomerular disease patients to how having CKD in general affects bone health? Dr. Denburg: I don’t know that glomerular patients need to be considered separately so much as have their unique risk within the CKD population considered. By definition, even someone with normal renal function who has glomerular disease is at CKD stage 1. At a certain point, everybody starts losing bone. What kids come away with in terms of their skeleton by the time they enter the adult world is a huge determinant of their later fracture risk and other skeletal burden over time. You can never get that opportunity to address bone health back. You do accrue some cortical mass until age 30, but the majority of what you have is what you can accrue in your skeleton by age 18. Children and teenagers with glomerular disease have unique risk factors: high dose and long term steroid therapy, abnormalities in vitamin D metabolism, ongoing, persistent, heavy protein losses, and inflammation. There are a variety of risk factors that we can hopefully address. NKI: The computable phenotype is another project I know you’re working on, and it sounds like it could be a game-changer. What is your role in that project and what about it excites you for the future of glomerular disease? Dr. Denburg: That’s a very exciting avenue of research. Much of my effort on that is supported by the NephCure Kidney Network. The computable phenotype is a way of identifying patients with glomerular disease through electronic health records (EHRs). It’s being developed in collaboration with PEDSnet [a large clinical data research network, composed of eight health institutions], so it represents over 5 million children and adolescents. The idea is that by running a computer programming code with essentially the push of a button, you can very rapidly say, here are the approximately 3,000 kids who have glomerular diseases across PEDSnet. And this is not static data, this is real life clinical care data. You could run the programmatic code again three months later and identify new cases. This is opposed to the traditional method where someone is sitting and going through the charts at each institution, which is not very time or cost effective. The idea is that this is a means of rapid cohort identification. You can do observational studies on this population’s de-identified data. Or, with regulatory approval, you can contact patients and invite them to be in observational studies and clinical trials. You can also do trials in a more pragmatic way: you can invite patients to participate in a study where they don’t necessarily have to be followed by a typical regimented protocol with extra clinical visits, which is very laborious and cost-intensive. Instead, using this method, if we wanted to do a larger vitamin D study, we could consent individuals for a study and say, we’re going to randomize you to a group that either gets a lot of vitamin D or a group that gets a little vitamin D, abut then after that all your care is going to be your routine care with your clinician. Instead of having you come to separate appointments to track the effects of the vitamin D levels, we’re going to capture your data in regards to this study through your EHR. And we’ll leave it up to your own nephrologist to follow your levels and change your dosage. That’s what I mean by a pragmatic trial. I should say, the study has to lend itself to that—a high risk, new drug study is never going to be implemented in this manner. NKI: And that more closely mimics real life; how a treatment would be used in real life vs. in a highly-regimented protocol. Dr. Denburg: Right—so you lose a little of the very protocolized follow up, but you gain the real-life applicability and generalizability. NKI: What impact did receiving the NephCure-ASN award have on your research? Dr. Denburg: It was really mission-critical. I was a junior person, two years out of fellowship at that point, and it enabled me to build a research program. It helped me in getting my Career Development (K) Award from the National Institutes of Health, and the combination of those two awards allowed me to develop my research program and to have the ability to pursue multiple directions. I like that I get to do patient-oriented research where I’m directly enrolling patients in studies of vitamin D treatment or assessing bone quality through imaging, but then I can also do studies where I’m accessing robust samples from NEPTUNE and entering this large data world. There are things you can do in each that really complement the other. And it’s the way to push things forward, moving between the analysis of large sources of data and then taking it back to the patient and vice versa. So I’m very grateful for the funding. I feel lucky. As pediatric nephrologists, Nephrotic Syndrome makes up a significant portion of patients we see and treat. Being a clinician who sees these patients really helps in keeping you attuned with what needs to be addressed from the research side—the patient care really drives the research questions. We were delighted to learn more about Dr. Denburg’s research. Check back at www.NephCure.org to stay updated on her soon-to-be published work and other advances in the field. Thank you for your passion and commitment to improving the health of patients with Nephrotic Syndrome, Dr. Denburg! Dr. Michelle Denburg, MD, MSCE, is an Assistant Professor of Pediatrics at the Perelman School of Medicine of the University of Pennsylvania and the Children’s Hospital of Philadelphia. Dr. Denburg’s research focuses on bone and mineral metabolism in childhood kidney diseases, including chronic kidney disease (CKD), glomerular disease, and urinary stone disease. In particular, she has pursued translational work in vitamin D-mediated innate immunity in nephrotic patients and ancillary studies of vitamin D metabolism and vitamin D-binding protein in pediatric patients with CKD. Her collaborative studies have focused on vitamin D metabolism and bone structure in children with CKD, nephrotic syndrome, and inflammatory bowel disease. Dr. Denburg’s study of incident fracture risk in the Chronic Kidney Disease in Children (CKiD) cohort was the first to evaluate the burden of fractures in a large pediatric CKD cohort. She is a co-principal investigator in a project of the CKD Biomarkers Consortium that seeks to identify novel biomarkers for CKD progression in children. She has conducted several population-based studies of fracture risk in chronic diseases and CKD epidemiology using The Health Improvement Network (THIN) Database. She also has led the development of and serves as co-principal investigator of a Pediatric Glomerular Disease Learning Health System (LHS) within the PEDSnet clinical data research network. Dr. Denburg attended medical school at the Weill Medical College of Cornell University and received her Master of Science in Clinical Epidemiology from the University of Pennsylvania.
Why I Do What I Do: Spotlight on Michael Levine, NephCure Vice President October 2, 2017 by Lauren Eva Michael with his son, Matthew. NKI: How did you first find out about NephCure? How did you get involved? Michael Levine: I think my wife Dana found NephCure on the internet. That was 12 and half years ago, when my son Matthew was first diagnosed with FSGS. I think it was a few months after the diagnosis that we got connected. The first event we got involved with was probably the Countdown to a Cure gala, with Ron Cohen and everybody from New York. NKI: You’ve been involved both directly as a chair for so many of our events, like Countdown to a Cure New York and All In For a Cure on Long Island. What’s been your favorite NephCure event? Michael: Well, each one is different. Quite frankly I love them all, because they all serve a purpose: to create awareness all over the country and the world, and to bring exposure to NephCure, FSGS and Nephrotic Syndrome. And obviously, the events raise dollars to try and create this miracle of a cure. I guess my favorite event is Countdown to a Cure, because NephCure gets to put its best foot forward to so many people. Over 500 people attend, we raise over $600,000, and it’s just a very classy, professional event that is seen by so many families and patients around the country. It gives these patients and families hope. Seeing what NephCure does with that dinner, and meeting families from all over the world, it gives everybody so much hope that if we could do more events like that, a miracle of a cure is attainable. (L-R) Michael’s wife Dana Levine, special guest Cuba Gooding Jr, and Michael at the 2014 Countdown to a Cure gala. NKI: You have raised an incredible amount of money in the 12 years that you have been volunteering with NephCure, on the NephCure board, and chairing for so many events. Does asking for money get any easier with experience? Michael: It never does. The only thing that gets any easier is the knowledge of what we’re doing. Talking about what NephCure does and what our goals and dreams are, that gets easier because I talk about it so much. And telling my story gets easier only because it’s so engrained and enveloped in me. But for me, asking for money is not something that gets any easier. It’s very hard for me to do because I’ve never been a person who is big on asking for help. Many of the fundraising experts say that it should get easier, because you’re asking for money for a very good reason: you’re asking for money to fund a cure and save lives. But for myself personally, it never gets easier. NKI: Is there anything that you think to yourself just before you initiate that first conversation that helps you get past that feeling that it’s going to be tough to ask for money? Michael: Well every time I ask, I say to myself, “Think about all the warriors around the country and around the world battling FSGS and Nephrotic Syndrome.” All the people who reach out to me on Facebook with their families’ and children’s stories. All of the Humans of NephCure stories on Facebook, which I read every single week. You know, sometimes it’s not easy. Sometimes it’s overwhelming. And there are some days that I say, I can’t do this anymore. But then I think about all the families and children that are battling this horrible disease, and I don’t want them to go through the same living hell that my family has gone through over the past 12 years. So that’s my motivation. There are two phrases that I always carry around when I do this. First of all, when I find out that somebody has made a donation to NephCure for an event that I’m a part of, I always write back to them, “You’re an angel on our shoulders. You allow us to dream that a miracle of a cure is possible. You give us hope against the greatest odds, and you give us the strength to fight every day.” I write that to everybody. Matthew Levine, Yankees Manager Joe Girardi, and Michael at a Yankees pre-game press conference this year. I also often write to people, “We are delivering dreams, miracles, wishes, and cures to the warriors around the world battling two devastating kidney diseases, FSGS and Nephrotic Syndrome. These diseases have no cure, and destroy kidneys, families, and lives in their path.” Whenever I think of those things—that’s what motivates me to tell my story to ten people a day, and to ask people for help and to donate money, and to ask people to attend all these events around the country. NKI: What kind of advice would you give someone who wanted to do a big event, like a gala, for NephCure? Michael: The first year is the toughest. You just have to get through that. After the first year, when people see how heartfelt you are and see that you’re trying to deliver dreams, miracles, wishes, and cures, it will get easier. NephCure, FSGS and Nephrotic Syndrome need a ton of awareness and exposure and a ton of dollars. So grab some friends, family and business associates, and say, “I want to save some lives today. I want to create a miracle of a cure for the children and adults battling FSGS and Nephrotic Syndrome.” Whether it’s a bowling tournament, a sporting event, a golf outing, a lemonade stand, a gala, a dinner, just grab some people, form a committee, start having some meetings, and have that committee invite their friends, family, and business associates to the event. It’s like a mushroom, or a plant—it will grow. After you get through the first year, everyone who attends in year one will invite more people for year two, and it just expands. If you want to create a miracle of a cure for FSGS and Nephrotic Syndrome, just create an event. You can do it anywhere in the world. You might not raise that much money, awareness, or exposure in year one. But it’s the stepping stone to years 2, 3, 4, and 5. And maybe by year 4, 5, or 6 you could be like the Tampa Pig Jig, where they’re raising $800,000 and have 6,000 people attending their event. You can’t get discouraged; you just have to fight through it. Just get started. I think that’s the best advice I can give. NKI: You make something that might seem complex to someone who has never done it before seem very attainable and possible. Michael: It’s very possible. You could start an event anywhere, and every dollar you raise brings us one dollar closer to a cure. You’ll get so much out of it, knowing that, and all of your friends and your family can be involved in it with you. And when the event is over each year, the fulfillment of saving lives by doing an event is incredible. I would just like to add that NephCure has been a godsend to my family. With all the events that NephCure puts on—the Nephrotic Syndrome Symposia, the conference in Chicago, and all the walks and events and the visits to Capitol Hill—all these events bring awareness and exposure to the disease, and they allow us to dream that a miracle of a cure is possible. All these events allow us to participate in so much and know that we’re making a difference. The doctors that are involved, the scientific advisory board, everybody at NephCure—my family considers them angels on our shoulders because they give us hope that one day a miracle of a cure can be found. You really are making a difference. And I would just stress to people to get involved. People think NephCure just needs money. And we certainly do. But there are so many other ways to help—with your businesses or your workplace; it doesn’t always have to be money. Money is great, but people can also donate their time, goods, services, and supplies. They would be giving hope to so many people. Just get involved in some way. Michael and other NephCure board members and supporters ring the opening bell at the New York Stock Exchange on Aug. 15th, 2014. We are so grateful and lucky to have someone as committed as Michael on our board. Michael continues to devote an incredible amount of time and energy to NephCure each year. We salute you and your work, Michael! Thank you for your dedication to finding better treatments and a cure for all who suffer from FSGS and Nephrotic Syndrome. The Countdown to a Cure gala will be on Pier Sixty in Manhattan on Nov. 9th at 6pm. We invite you to attend, meet Michael, and help us change lives. You can visit the event page here. If you have any questions, please contact Lorraine Mackin at LMackin@NephCure.org.
Advocacy Alert: Action Required September 20, 2017 by Kylie Karley Senators Lindsey Graham (R-SC), Bill Cassidy (R-LA), Dean Heller (R-NV), and Ron Johnson (R-WI) recently introduced legislation known as Graham-Cassidy to repeal and replace the Affordable Care Act (ACA). The hope of these lawmakers was to hold yet another vote on repeal before October 1st, so a simple majority (51 votes) is all that is needed to pass the measure. Unfortunately, the Graham-Cassidy proposal is more extreme than other recent Senate proposals and would be particularly harmful to individuals and families impacted by chronic health conditions. Specifically, the new proposal would: Allow insurance companies to charge more for those individuals with pre-existing health conditions Allow states to more easily opt out of requiring quality health insurance options and comprehensive benefits Expand the ability for individuals to purchase low quality health insurance benefits in lieu of more comprehensive coverage Eliminate the individual and employer mandates Dramatically reduce the federal commitment to Medicaid expansion Eliminate the Prevention and Public Health Fund While this effort was initially dismissed by many as a “Hail Mary,” it has quickly gained support and could be voted on next week. In order to protect patients with chronic conditions, please contact your Senators and ask them to oppose the Graham-Cassidy repeal and replace proposal. Take Action Contact the health Legislative Assistants (LAs) in the offices of your two U.S. Senators and use the message below for a voicemail or brief e-mail. The contact information for your Senate offices can be found at Senate.gov. Template For Emailing / Calling / Faxing Your Senators Dear _______, My name is _________ and I am a constituent from [home town]. On behalf of patients with chronic health conditions, I urge the Senator to oppose the Graham-Cassidy healthcare proposal. This proposal would be absolutely devastating to individuals and families affected by chronic illness that rely on access to quality, affordable health care. [Explain a little about your particular situation] Thank you for your consideration of my request. Please tell me how you have responded to my request. Sincerely, [Name] [Address]
NephCure Funded Research: Dr. Hani Suleiman August 1, 2017 by Lauren Eva Dr. Suleiman is using a Nobel-prize winning microscopy technique to look at the kidney cells injured in FSGS. In 2014, the Nobel Prize for Chemistry went to a group of scientists who’ve created a new technique to change the scale at which we are able to see cell structures. In the same year, NephCure awarded a Young Investigator Award to Hani Suleiman, MD, PhD, an instructor at the Washington University School of Medicine, to use this new microscopy approach to look at kidney podocyte cells. Recently, we spoke with Dr. Suleiman to hear about his work using this new microscopy approach, and how it might be used in the future to diagnose and potentially change how we approach creating new treatments for FSGS, Minimal Change Disease, and other diseases that cause Nephrotic Syndrome. Dr. Hani Suleiman in his lab. NKI: You received the Young Investigator Award from NephCure in 2014. Could you give us an overview on what you’ve been studying since receiving this grant? Dr. Hani Suleiman: Glomerular diseases like Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are diseases of the podocyte, an important component of the kidney’s glomerular filtration barrier. Studying podocytes in living tissue has been limited due to the types of microscopy techniques that we use. The problem with seeing and understanding the podocyte and its changes is in its scale: important structures in the podocyte range from 200-300 nanometers. This resolution is below the limit of conventional microscopy techniques. Thus, we have been hindered from studying in detail the molecular changes that accompany podocyte injury and proteinuria. Until the invention of super-resolution microscopy, the only way to view changes in podocytes after injury was to use electron microscopy techniques [electron microscopy was invented in the 1930s]. However, electron microscopy only allows us to see the structural changes in the podocyte. There is another technique that is capable, to some extent, to view the molecular patterns in podocyte structures after injury, but this technique has its own limitations. This is where super-resolution microscopy, a revolutionary new technique, comes in. We were the first people to adapt this technique to the kidney field. In kidney diseases such as FSGS and MCD, podocytes go though a massive change in their shape as they lose their foot processes and form what is called foot process effacement. This is when the finger-like protrusions that you see in a normal podocyte change and basically disappear. This usually accompanies a leaky glomerular filtration barrier, as the patient starts spilling protein in the urine (proteinuria). Proteinuria, by itself, is an important indicator that the kidney is not functioning correctly as a filter. Normal kidney podocyte. Foot process effacement is a phenomenon that we see in almost all podocyte injuries, no matter how the injury starts: whether it’s immune-related, MCD or FSGS. All these diseases have foot process effacement and are accompanied with a loss of the glomerular filter. In the paper that we just got accepted in the Journal of Clinical Investigation-Insight, we studied the molecular changes that accompany foot process effacement using super-resolution microscopy to try to understand the enigmatic phenomenon of foot process effacement and how foot process effacement is related to the cause of the injury. I think that, by mapping the earlier molecular changes in the injured podocytes, we can potentially intervene and stop this massive change and maintain the foot processes and the barrier. This effort may be a good first step towards actually interfering with the pathways that we think interplay with this phenomenon [i.e., a first step towards treating proteinuria at a molecular level]. And for that, super-resolution will be an instrumental technique, since we are able to see the molecular changes of the cell on a nanoscale. NKI: So podocyte foot process effacement is basically the fingerlike protrusions of the podocytes pulling up and away and leaving the podocyte with just the cell membrane. And without the fingerlike protrusions there, there’s nothing preventing the protein from leaking through the kidney? Dr. Suleiman: As a response to injury, we think that foot process effacement is a survival mechanism for the podocytes. Podocyte number, like neurons, is a fixed number, and they must survive throughout life as they don’t reproduce. We can speculate that podocytes sense the dangers around them and respond by changing their shape in order to hold on to the basement membrane tightly as a precaution, in order to not fall into the urine. As I mentioned earlier, foot process effacement is usually accompanied with proteinuria, indicating that the retracted podocytes are unable to cover the whole basement membrane and prevent the protein leakage. My work is to try to understand the earlier changes that cause the podocytes to go through this tremendous morphological change (i.e., foot process effacement), and how foot process effacement is related to the cause of the injury. I think that, by mapping the earlier molecular changes in the injured podocytes, we can potentially interfere and stop this massive change and maintain the foot processes and the barrier. Dr. Suleiman, top row, second from the left, at the 2016 St. Louis NephCure Walk. NKI: Are you mostly looking at mouse models right now? Dr. Suleiman: In our recently accepted paper, we studied podocyte injury in three different mouse models. We included a small group of human tissue samples of FSGS, MCD and diabetic nephropathy in the study. We found that, similar to our mouse injury models, injured human podocytes show molecular changes that involve the motor molecules, myosin IIA. As these results are in their early stages, I recently received a NEPTUNE (Nephrotic Syndrome Study Network) grant to study the biological significance of myosin IIA changes in human tissue samples. This study might allow us to find better diagnostic or prognostic tests for diseases such as MCD, FSGS and diabetic nephropathy. NKI: So what you’re saying is that you think one day we might be able to use the super-resolution microscopy technique to diagnose patients? Dr. Suleiman: Yes, I can see that the super-resolution microscopy will be instrumental in the future to diagnose and predict the outcome of diseases like glomerular diseases. The whole problem with imaging the podocyte in the past was the scale. Super-resolution, and the recently developed near super-resolution microscopy techniques, has the right scale to view the molecular changes in the podocytes. NKI: Did the NKI Young Investigator Award have a big impact on what you have been able to do? Where were you at in your research when you received it? Dr. Suleiman: Oh sure! That was my first grant ever. So for the last two years I have been relying on this grant to do my research. Of course, my previous mentor, Dr. Andrey Shaw, was highly supportive; I was still in his lab when I received the NKI award. This award has helped me publicize my work, refine my hypothesis and maintain my focus on the podocyte biology. It helped a lot. Thank you so much. We were thrilled to learn more about Dr. Suleiman’s research. Check back at www.NephCure.org to stay updated on his work and other advances in the field. You can also view his most recent article on the super-resolution technique here. Thank you for your passion and commitment to learning about glomerular diseases, Dr. Suleiman! Hani Suleiman, MD, PhD, is an Instructor in the Nephrology Division at the Washington University School of Medicine in St. Louis. Upon establishing the use of super-resolution microscopy, STORM in the kidney field, Dr. Suleiman has been focused on utilizing this technique to study various kidney diseases such as diabetic nephropathy, focal segmental glomerulosclerosis, and minimal change disease. In 2017, he received the Nephrotic Syndrome Study Network (NEPTUNE) Career Development Fellowship. Dr. Suleiman has developed new ways to image the podocyte’s actin cytoskeleton in both animal models and human. These methods will allow us to ask new questions regarding how podocytes regulate their unique shape and maintain their function throughout life.