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!