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.
Why I Do What I Do: Spotlight on Laci Weatherford, Volunteer Walk Leader August 1, 2017 by Lauren Eva Laci Weatherford is now in her 7th year as a volunteer leader for the St. Louis NephCure Walk. Her incredible efforts have helped grow the walk to a massive event, with more than 100 people in attendance and raising around $15,000 each year! We spoke to her recently to learn about her journey with FSGS and how she manages such a successful fundraiser. NKI: How did you become involved with NephCure? How long have you been involved? Laci at the St. Louis Walk in 2012. Laci: I believe the first time I found NephCure was in 2009 when I was diagnosed with FSGS. I researched on the internet and found the NephCure website. I must have provided my information and said I would like to get involved, because in 2011 I received an email saying they were going to have a walk in St Louis. The email asked if I would like to be on the committee. I said yes. The day I was on my first planning committee call, I discovered I was the committee, the only volunteer for the event that was about a month away. So that year I learned the very basics of putting together a walk and have been working on improving and growing our annual event ever since. NKI: Why do you devote your time and energy to this cause? If you feel comfortable explaining, what’s your personal connection to kidney disease? Laci: After I was diagnosed in 2009, I began my personal journey with FSGS and learned firsthand the terrible side effects of the drugs available and the lack thereof. I learned how precious the little things were and struggled to just get by day-to-day, enjoy my 2 year old baby, and take care of myself. I began to read more on the internet about this disease: sometimes it would be good and encouraging, sometimes not. It quickly became too overwhelming to read the stories from parents who had children struggling with these drugs and side effects. It broke my heart, and I felt it was so unfair. I had lived a good life up until my diagnosis; I enjoyed my childhood, but they were being robbed of simple joys. I received a referral for a specialist in NY and became so encouraged by his accomplishments and his knowledge of the disease. I have tremendous hope and belief the cure and proper treatments are out there. We just need the right people to have the right tools to make it happen. It takes a lot of work to put all the proper channels in motion, and I’m so grateful NephCure is there doing the work to keep progress in motion. I want to do what I can to help fund this process. Laci and members of Team Brayden at the 2016 St. Louis Walk. NKI: What’s the hardest part about being a walk leader? Laci: The hardest part is getting the word to participants. Since this is a rare disease, not many people have ever heard of FSGS or NephCure. Unless you or a loved one is personally impacted, then you are probably not looking for another charitable event to go to. I’ve got to find a way to find the patients and their families. Doctors aren’t willing to help most of the time because of HIPAA policies and various other reasons. NKI: What’s the best part? Laci: There is so much that warms my heart about the event. The first is my family. They drive 3 hours just to be in St. Louis with me on this special day. They also coordinate 75% of the activities and volunteer in any area I need. If it wasn’t for them, I literally couldn’t do this. Second is seeing the other patients. To see them smile and enjoy a day dedicated to them encourages me to keep going. I also love to see the growth in the event, which is the proof we are getting the word out there. My first walk had about 20 people and we raised around $2,400. The walk is now averaging between 100-120 people each year and we raise on average $15,000. That is just amazing to me. NKI: What has surprised you the most throughout your years of leading this walk? Laci: I’m surprised by how generous and easy is it to get donations. Most of the time all you have to do is ask. There are so many business that will gladly give you a gift card, services, or products to help you raise funds. There is no secret to fundraising or formula for getting donations—all you have to do is ask! Mostly likely you are going to get a yes. Laci, center, with family and friends at the 2016 St. Louis Walk. Congratulations and a big thank you to Laci and her supportive team for their incredible efforts each year! With their help, we are one step closer to finding better treatments and a cure for FSGS and Nephrotic Syndrome. We couldn’t do it without them! Interested in volunteering at a walk or creating a walk team? Great! Just email us at events@nephcure.org to get started.