More than 1 in 7 U.S. adults — about 36 million people — live with chronic kidney disease. Yet the kidneys remain among the most understudied organs in medicine. NIEHS physician-scientist Jason Watts, M.D., Ph.D., is working to change that. A Stadtman Investigator since 2020 and recently named a National Institutes of Health (NIH) Distinguished Scholar, Watts leads a research team that is exploring how environmental exposures — such as heat, pollutants, and heavy metals — can trigger kidney injury at a molecular level.
One major focus of his work is understanding how stress from muscle breakdown, known as rhabdomyolysis, can damage kidney function. This condition — which can occur during military training, natural disasters, or even intense workouts — floods the bloodstream with a protein known as myoglobin. Watts is working to show how a component of that protein, called heme, plays a central role in harming the kidneys by changing the way genes are transcribed.
Environmental Factor recently spoke with Watts to discuss how his journey began, what he has discovered thus far as a researcher and physician, and why he cares about kidneys.
Watts leads the Transcriptional Responses in Disease Group, is an adjunct assistant professor of medicine at Duke University, and treats kidney patients at the Durham Veterans Affairs Medical Center in North Carolina. (Photo courtesy of Steve McCaw / NIEHS)
Environmental Factor (EF): What first sparked your interest in science?
Watts: I was one of those kids who genuinely loved learning. In elementary school, I was really into nonfiction — volcanoes, dinosaurs, rocks. I thought summer vacation was a waste of time and that we should do school year-round, which my older sister thought was insanity!
The real turning point came in seventh grade when my science teacher recommended me for a summer program at Howard University. I took the Metro into D.C. with another student for this two-week program, and one of the highlights was isolating DNA. I still vividly remember adding ice-cold ethanol and watching this stringy precipitate emerge from a clear solution. I thought, “This is Watson and Crick’s nucleic acids right here on the end of this Q-tip!”
My goal as a kid was to know everything. Then, at some point, you realize there’s too much stuff to know — you can’t be the smartest person in the world. What you can be is the first person to know something. That’s very appealing. And then when things go well, you discover something important, something that matters to other people. Then you give that knowledge away and go find something new to discover. To me, that’s the draw of science.
EF: How did you end up focusing on kidneys, of all organs?
Watts: Two things drew me to kidney research. First, I learned about the kangaroo rat in biology class — this desert animal that never has to drink water because its kidneys are so efficient at concentrating urine. The idea that an organ could be that powerful fascinated me.
Second, high blood pressure runs in my family, and I became interested in how the body handles salt and water. The genetics of hypertension often comes down to mutations in proteins that work in the kidney. By college, I was thinking about nephrology, though it wasn’t until after medical school that I found my specific niche combining gene regulation with kidney function.
EF: Your research connects environmental heat exposure to kidney disease. Can you explain that connection?
Watts: It starts with muscle breakdown, or rhabdomyolysis. When people do intense physical work in hot conditions — like military training, construction, or farmwork — their muscles can break down and release a protein called myoglobin into the blood. This protein contains heme, a molecule that we’ve known since biblical times can hurt kidneys, but we didn’t understand the mechanism. I see this clinically all the time as a doctor treating patients with kidney injury and disease. I remember during one week last summer when a half-dozen veterans came into the Durham Veterans Affairs Medical Center with kidney injury from rhabdomyolysis. It’s incredibly common.
EF: What have you discovered about how heme actually damages kidneys?
Watts: We found that heme can stick to folded structures in RNA and DNA called quadruplexes — imagine them like molecular Big Macs. When heme binds to these structures, it acts like a toothpick that keeps the sandwich from falling apart, making the quadruplexes too stable.
This is a problem because these structures can block the cellular machinery that reads genes and makes proteins. When that happens in the mitochondria — the cell’s powerhouses — cells can’t produce enough energy. Since kidney cells require enormous amounts of energy to filter blood and maintain fluid balance, this leads to kidney dysfunction.
EF: Why are kidneys particularly vulnerable to environmental exposures?
Watts: Kidneys are essentially the body’s waste management system, and they’re incredibly active. Both kidneys combined weigh about as much as your heart, but they receive 20% of your blood with every heartbeat — about four times more blood flow per gram of tissue than your heart gets. To put this in perspective, about 400 gallons of blood flow through your kidneys every day, and they filter about 40 gallons of that. From those 40 gallons, we only urinate about 1.5 quarts. That’s an enormous amount of processing, which means environmental toxins get concentrated in the kidneys.
So, if you’re breathing in air pollution from living near a highway, exposed to heavy metals or other contaminants, these substances end up in the kidneys and can accumulate over time. The kidney cells responsible for reabsorbing nutrients and water just “hoover up” everything, including toxins.
EF: What keeps you motivated to do this research?
Watts: The fact that we have no specific therapy for acute kidney injury, despite it being incredibly common. Five percent of all hospitalized adults and half of intensive care patients develop acute kidney injury. Yet our standard treatment for acute kidney injury is essentially “stop what’s hurting the kidneys and wait to see if they get better.”
What excites me, though, is taking small, nerdy, esoteric discoveries about how molecules fold and showing how they’re consequential to people’s health. The number of people focusing on nucleic acid structure in the context of kidney disease is very small — which means there’s huge potential for discovery.
(Marla Broadfoot, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison.)
