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Chicago via Canada

Quaggin Brings Innovative Kidney Research, Passion to Feinberg Cardiovascular Research Institute

It had to be something in his bloodstream. But that was as far as the literature could take her.

For Susan Quaggin, MD, Charles Horace Mayo Professor of Medicine, it was enough to spur a career of exploration.

“I quickly realized that you could either pursue textbook medicine, or you could ask questions at the bedside that require answers not found in published material,” says Quaggin, of her residency and fellowship at the University of Toronto in the late ’80s. “In nephrology at the time, there were very limited treatment options available, and in order to develop new therapies and new ways to diagnose patients, it was absolutely clear that we needed to develop a better understanding of how diseases occur.”

One of her first cases was that of an 18-year-old man. Healthy just weeks before coming to the hospital, he had developed an aggressive form of kidney disease.  A year later, Quaggin watched as he lost a transplant.

“His disease recurred right there on the operating table,” she recalls. “As soon as he got his father’s kidney, it functioned well but it started spilling large amounts of protein into his urine. The idea was that he had something circulating in his bloodstream that was attacking the kidney. It’s an issue that my lab continues to study nearly 25 years later,” says Quaggin, who in June received the Alfred Newton Richards Award from the International Society of Nephrology for basic science research.

Throughout the past two decades, Dr. Quaggin’s research has contributed immensely to the increased understanding of common kidney disease. In 1997, her lab discovered a gene, POD 1, that is vital for the development of healthy hearts, kidneys, and lungs. The gene is required for formation of specialized glomerular cells in the kidney known as podocytes, which are the primary target of injury in diabetic disease. Podocytes are a major component of the kidney filtration barrier, responsible for removing excess fluid and solute from the blood, and preventing the loss of things the body needs, like protein. And it was these cells – the podocytes – that were attacked in the 18-year-old patient.

This image of a developing kidney shows the podocytes in green, endothelial cells in red, and cell nuclei in blue.

“The work in my lab focuses on these little filters in the kidney and the associated podocytes, which cover the glomerular capillaries and normally keep the protein in the blood and not in the urine,” says Quaggin, chief of nephrology and director of the Feinberg Cardiovascular Research Institute (FCVRI). “During the past quarter century we have gained an incredible understanding of the sorts of things that cause this protein spilling. In my own lab, we have uncovered a few of these pathways and are now working toward new therapies.”

Pivotal Shifts

As a teenager, Quaggin knew she wanted to pursue a career in medicine. But it was pets not people that she imagined treating.

“Then I met my future father-in-law, who is the epitome of a great family doctor – bikes to work, makes house calls,” she says. “I was always interested in science, but from that point on I knew that medicine was the path I wanted to follow. I volunteered throughout school at area hospitals and went to college with a goal of entering medical school as quickly as possible.”

Born and raised in the suburbs of Toronto to parents who moved there from the Isle of Man, Quaggin recalls her childhood as typically Canadian.

“Everybody plays hockey and you grow up living next to hockey players,” she explains. “My next-door neighbor was a New York Ranger, and I still have Blackhawks cards from the ’70s.”

The decision to leave Canada, and her parents, who arrived two decades earlier in search of work and in lieu of finishing high school, did not come easily.

“It was a big decision because my daughter had just been born,” says Quaggin, who also has two sons. “I became interested in the burgeoning field of genetics and so left Canada to go to Yale, but I always planned on going back.”

Susan Quaggin, MD, director of the Feinberg Cardiovascular Research Institute, with her husband, Kevin Smith, at the 2013 Reunion Ball.

Seminal Finding

“A major challenge for us today is that diabetes is the most common cause of kidney failure in North America and we still have nothing really, other than managing blood pressure and controlling blood glucose, to treat it,” she says. “In searching for ways to prevent kidney disease in diabetics, our lab has recently uncovered a new pathway, a novel mechanism of how the kidney filters stay healthy, and it turns out it has to do with the regulation of the podocyte’s cell shape.”

The findings uncovered new information about sFLT1, a key protein that binds vascular endothelial growth factor (VEGF)—and that causes blood vessel growth. The protein binds to the surface of the podocytes, triggering a cell shape change required for normal urine filtration.

Published in Cell in October 2012, this discovery could potentially impact drug therapies and treatment options for the millions of Americans who suffer from kidney failure.

The Impact of Others

A soft-spoken chief, who leads in large part by acting as a conduit for collaboration, the Canadian isn’t shy about crediting her mentors for where she is today.

“When I started my fellowship, the first rotation I had was in nephrology, and there I had a number of role models who were clinicians and also academic physicians,” she explains. “There were also a number of very important encounters with patients that directed me toward nephrology as a career.”

Dr. Quaggin's current lab staff at Feinberg includes (front) Chengjin Li, Tuncer Onay, Christina Bartlett; (back) Ben Thompson, and Ashish Ghosh. Quaggin is still in the process of moving other members of her Toronto lab to Chicago.

During that first year, Quaggin met a physician-scientist, Mitch Halperin, MD, who helped introduce her to the idea that science could help the very patients she was treating.<

Thanks to such inspiring role models, “much of what we did as fellows was translational research,” she recalls.” We would be exposed to unexplained cases and try to get to the bottom of them. From that point on, I quickly decided that I also wanted to be a scientist.”

In 1998, Dr. Quaggin became an assistant professor of medicine at the University of Toronto. Nine years later she was named the Gabor-Zellerman Professor, a post she held until coming to Feinberg earlier this year.

Back to America

Not fond of heights, Dr. Quaggin found her high-rise apartment in downtown Chicago took some getting used to. But as equipment, lab members, and eventually, her family arrived in the Windy City, she has settled into many roles, including leadership of the Feinberg Cardiovascular Research Institute

Renewing its focus and expanding its research breadth, Quaggin sees the FCVRI as an institute of collaboration.

“We’re going to really grow the partnerships across the Chicago and Evanston campuses to help facilitate some of the great research already taking place,” she explains. “By promoting the scope of investigation, we will explore the basic mechanisms of vascular development and maintenance that are critical for function, not only of the heart, but of the eye, kidney, and lung vessels, and how they interact with one another.”

“For me, the opportunity to come here, particularly at this time, is what made the decision so worthwhile,” she says. “As the medical school continues to invest in research, it’s going to drive new discoveries.”

Susan Quaggin, MD, with her husband, Kevin Smith, and their children: Patrick, 18, Jessica, 20, and David, 14.

Susan from Chicago

Having travelled the globe to discuss her groundbreaking research, Dr. Quaggin considers meeting new scientists far more important than her own notoriety.

“I prefer to be introduced as ‘Susan from Chicago,’ nothing more,” she says. “Building those new connections that may help springboard the next set of experiments in the lab is one of the greatest aspects of science. My passion has always been research and has always been driven by patients.”

And Quaggin has never tried to separate the two.

“Rounding in the dialysis unit and talking with patients provides the motivation for everything I do,” she explains. “It’s been an incredible journey to see how nephrology has changed over the course of my career.”

As for the young man who helped engage the curiosity of a 20-something fellow? He is a successful businessman receiving dialysis three times a week and the type of story that inspires Quaggin in her pursuit of science and medicine.