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Bioengineered Organs & Kidney Diseases with Susan Quaggin, MD

Susan Quaggin, MD, and a team of scientists with expertise in stem cells, blood vessels and developmental biology are accelerating the development of bioengineered kidneys. But that’s not all. Quaggin talks about the projects and science underway that could lead to new treatments to prevent, manage and cure kidney diseases.

 

Norrina Allen

"What I like to say to all the residents, housestaff and patients is that we are now entering the era, a new era for kidney disease, where we're going to see incredible advances. It is a very, very exciting time for our patients and for us as caregivers."

Susan Quaggin, MD

  • Director, Feinberg Cardiovascular and Renal Research Institute

  • Chief of Nephrology and Hypertension in the Department of Medicine

  • Charles H. Mayo, MD, Professor

  • Director, Northwestern University George M. O’Brien Kidney Core Center (NU GoKidney)

Episode Summary

More than 30 years ago, fresh out of medical school and on her first day as an intern, Susan Quaggin, MD, was assigned to the nephrology ward. One of the first patients she met in the emergency room that day impacted the focus of her career forever.

Susan Quaggin: "I met, in the emergency room, an 18-year-old boy. He had been perfectly healthy up until a couple of weeks prior and then had gained about 20 pounds of weight and this was all fluid and it turned out that the reason he had gained all this fluid, he had a very aggressive form of a kidney disease, something circulating in his bloodstream that was attacking the glomeruli or the little kidney filters that are present in the kidney."

There were no treatments available. That patient and others that came after him were among the people who inspired Quaggin to pursue nephrology as a career.

Susan Quaggin: "Not only because of the patients and the mentors I met along the way, but (also) because of the big opportunity and need to fill some of those gaps in diagnosis and treatment."

Since arriving at Northwestern University in 2013, Quaggin has been making a major impact on the medical school's kidney research programs. She is the director of the new Northwestern University George M. O’Brien Kidney Core Center (NU GoKidney), one of eight such programs in the country supported by an award from the National Institute of Diabetes and Digestive and Kidney Diseases, within the National Institutes of HealthThe center’s ultimate goal is to ensure that potential therapeutic targets for kidney diseases are identified, tested in preclinical studies and advanced to first-in-human studies so that the pipeline for therapeutics development in nephrology is enhanced.

Among the projects taking place in her lab is the development of bioengineered kidneys. Her group, along with Jason Wertheim, MD, PhD, and his team, are growing tiny mouse kidneys in a dish. Quaggin says such organs could be made from human skin cells or cells from a person's urine. Others across the world are growing such organs, but Quaggin and her team are also focused on growing blood vessels for these kidneys, a missing piece of the bioengineered puzzle.

Susan Quaggin: "I like to use the analogy, it's sort of like a toaster without a plug. So if you think about the miniature kidney as being the toaster without the blood vessels, there's no plugs, so it can't function. We can't hook it up to the rest of the body. So, one of the things that we've been working on in and the lab and for many years we've been very interested in the blood vessels that play very specific roles in the kidney. So we've done a lot of, of background work and now the goal with some very talented young trainees and other individuals in the lab is to really coax those blood vessels into these miniature kidneys with the ultimate goal of having these functional bioengineered kidneys."

Her team uses CRISPR-Cas9 technology to use genome editing in bioengineered kidneys or the cells that give rise to the kidneys, so that they can drive and give the instructions for the blood vessels to make it to the right place and to pattern the kidneys properly. 

Susan Quaggin: "There's a relatively large group working on these sorts of projects and tackling them together in a collaborative manner here at Northwestern."

Uncovering the genetic roots of congenital glaucoma is another project Quaggin is working on. A lot of kidney diseases are related to eye diseases. In a two recent publications, she and collaborators discovered mutations that cause improper drainage and a buildup of ocular pressure leading to one form of congenital glaucoma and identified a path toward future treatments for the disease.

Susan Quaggin: "This has led us together with the nanomedicine folks up on the Evanston campus and the chemistry folks (on the Evanston campus) to develop a biotech company. We have a new lead compound and eye drop in development to treat this severe form of glaucoma and also some of the more common forms of glaucoma with the hope that we'll be able to preserve vision. What's interesting, the same small molecule, we are actually repurposing for the kidney and it protects the kidney as well."

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