Tennis is a huge part of medical student Ryan Denu’s life. Dating back to his days as an undergrad at the University of Wisconsin, he loved tennis. His passion for the game is evident: He played during high school in Brookfield, Wisconsin and on the club team at UW–Madison while studying molecular biology, earning his bachelor’s degree in three years. He even became a tennis official in 2009, overseeing Big Ten matches and some professional tournaments.

But playing and officiating wasn’t enough. He was troubled by barriers to participation; the sport needed to grow its demographics, and more kids needed to play.

It wasn’t an idle thought: characteristically, Denu did something about it.

Ryan Denu
Ryan Denu

In 2011, just prior to starting medical school and a PhD in cellular and molecular biology at the UW School of Medicine and Public Health, he created a low-cost youth tennis program for 5- to 14-year-olds. It consists of eight, one-hour weekly sessions in the winter at Nielsen Tennis Stadium on campus, across the street from the classrooms in which he would soon be studying.

As any aspiring researcher would, he applied for a grant to pay for the program. It was denied. However, the United States Tennis Association discovered his program and agreed to fund it. Kids receive a racket, ball and a shirt to play in. After eight years – during medical school and PhD studies – the program now enrolls 200 children, and he maintains it to this day.

“It just keeps growing,” Denu said. “I have a crazy-long waiting list.”

Now he sees some of the children he’s mentored playing in high school, and you can hear his passion when he talks about it; even parents of the kids started playing.

“It’s just been a really fun experience,” he said.

'Making the biggest impact'

For Denu, putting feet to dreams is a pragmatic activity. When contemplating the field of medicine, he said, “I was thinking, how can I make the biggest impact I can during my time here on this earth?”

While pursuing his medical degree, he would author two legislative bills to address radon-induced lung cancer in Wisconsin, become a student representative to the American Medical Association House of Delegates, and discover a genetic mutation linking breast cancer to a rare genetic condition.

It was that last point, that put Denu, 28, in extremely rare company. Last month, he was named a 2019 STAT Wunderkind – one of only 22 in the nation. He was one of only five honorees hailing from public institutions.

STAT is a national life sciences and medicine news outlet produced by Boston Globe Media. The Wunderkind award has been given since 2017 to researchers who are “on the cusp of launching their careers but not yet fully independent … as they attempt to answer some of the biggest questions in science and medicine.”

Ryan Denu and Mark Burkard
Ryan Denu and Mark Burkard

Mark Burkard, MD, PhD, associate professor of medicine and associate director of the Medical Scientist Training Program at the UW School of Medicine and Public Health, nominated Denu to be one of the hundreds of nominations.

“He’s amazingly bright, productive and very upbeat,” he said.

A dual dedication to medicine and research

Denu was accepted into the Medical Scientist Training Program in 2012, which provides both MD and PhD training. After his first two years of medical school, he joined Burkard’s lab to perform the PhD component of the program over the next four years, and then shift back to the final two years of medical degree training.

His PhD work centered on the impact of centrosome amplification on the biology of cancer cells.

While working in Burkard’s lab, one project in particular earned him Wunderkind status.

One day Burkard asked Denu if he wanted to visit with a 31-year-old woman with Nager syndrome, a very rare genetic disorder that impacts physical development. The patient had endured multiple surgeries during childhood. Upon reaching adulthood, she developed bilateral breast cancer.

Burkard told Denu this was a chance to meet someone with Nager syndrome because he may never see someone with it again, according to Denu.

“I really didn’t think anything of it,” Burkard said.

But, Denu was struck by the unlikely combination of diagnoses.

Perhaps, he thought, the woman had an inherited genetic mutation that greatly increased the risk of breast cancer. But that turned out not to be the case. So, how was it that she was so unfortunate to have experienced both bilateral breast cancer at such a young age in addition to Nager syndrome?

He found the answer: the events were associated with each other. Genetic analysis showed that mutation that caused Nager syndrome likely also caused breast cancer.

“She had a mutation of a splicing gene; we see this in all types of cancer, and now we are trying to figure out why it caused this cancer when she had no other genetic predisposition,” he said.

Burkard and Denu hypothesized that her inherited mutation in the SF3B4 gene caused the cancer. To test the idea, Denu immediately published a case report and set up meetings with UW biochemistry and bioinformatics colleagues who study RNA splicing mechanisms.

He also successfully applied for a $10,000 Clinical Research Pilot Award Program grant from the UW Institute for Clinical and Translational Research to fund his work into the SF3B4 gene.

Next, he set up a teleconference with the primary author of the foundational publication on Nager syndrome genetics and contacted the national Foundation for Nager and Miller syndromes.

The goal: find another patient somewhere with the same genetic condition with breast cancer.

He found one.

This led to Denu writing an Institutional Review Board protocol to seek approval for collecting tumor samples and skin biopsies from the research subjects to grow induced pluripotent cells, which would allow further study. Then, he coordinated with the two individuals to enroll them in his study and collect specimens. Finally, Denu coordinated with a team of UW researchers to generate induced pluripotent stem cells from the skin biopsies.

He assembled the UW–Madison team in less than a week.

“It’s an example of how great [UW–] Madison is,” Denu said.

To Burkard, however, this amazing discovery isn’t what sets Denu apart.

“[Denu] has had a sustained impact on me and my research group.” Burkard wrote in a residency program application support letter for Denu. “His greatest impact has been to teach me and lab trainees how to be a part of a productive team.”

Ryan Denu

Even after earning his PhD, and formally leaving Burkard’s lab, he returns to work on various projects. And that seems just fine with him.

“I just feel lucky to be working with this guy, frankly,” Burkard said.

The academic career of a Medical Scientist Training Program student is long: undergraduate study followed by eight years in the MD/PhD program. Denu hopes to enroll in a physician-scientist track residency program that includes two years of clinical training in internal medicine followed by additional clinical and research training in medical oncology.

A lot has happened along the way; he met his wife Stefanie as a junior, and left a lasting legacy at UW–Madison.

And that legacy is not just at the institutional, state or national levels.

In his tennis life, he would start each session asking the kids why they love tennis. One little girl, day after day, would answer “bananas.” His mind and heart went to work.

Prior to the next session, he purchased a large quantity of the yellow fruit and placed them all over the tennis court. Upon arrival, “The look on her face was priceless,” Denu said.