Constance Chu’s Joint Ventures

Constance Chu’s future in medicine was sealed during a memorable moment in the operating room. 

The late Henry Mankin, then chief of orthopedic surgery at Massachusetts General Hospital, had invited her to join him on a case before she had even done her surgery rotation. Chu, MD ’92, remembers Mankin unwrapping a femur taken from a cadaver. It looked to her like something out of The Flintstones. He proudly showed it to her as he raved about the smooth, pristine expanse of cartilage on the end that forms the knee joint.

Then Mankin turned serious. He quietly stressed to Chu a critical limitation of cartilage: It doesn’t heal. “He told me that nobody had been able to figure out how to heal cartilage, looked at me intently right in the face, and added ‘yet,’” Chu recalls. “Then he smiled, and I felt the gauntlet drop at my feet.”

Chu, who was a third-year medical student at the time, took Mankin’s words as a welcome challenge and became an orthopedic surgeon. Today, as a physician-scientist, she divides her time between helping patients with knee injuries and conducting research on how to better repair and rejuvenate joints.

“As a surgeon, I go into the operating room, fix what’s broken, and know that I solved a patient’s immediate problem — and the things I can’t solve with surgery provide the inspiration and motivation for my research,” says Chu, a professor and vice chair of research in the Department of Orthopedic Surgery at Stanford University and the director of the Joint Preservation Center and chief of sports medicine at the VA Palo Alto. “I feel fortunate to be able to put these two very different skill sets together.”

Drawn to service at a young age, Chu completed her undergraduate degree at West Point. There she gained leadership skills that have served her well in medicine. After West Point, she spent five years as an intelligence officer in the Army. As commander of an imaging intelligence unit, Chu used computational tools to identify important features of detailed images, skills she now uses to advance quantitative interpretation of MRIs.

Chu wasn’t planning on being a physician until she unexpectedly lost her father to lung cancer in her first year of military service. As Chu stepped up to support and mentor her younger sister — a first-year biology major at Harvard College — she became intrigued by medical school. “I felt that as a physician, I could have a more direct positive impact on people. I really liked the idea of going home each day and knowing that I helped someone improve their health,” she says.

The things I can’t solve with surgery provide the inspiration and motivation for my research.

At HMS, the pull to orthopedics began during a rotation in the pediatric emergency room at Mass General. Chu brought a boy with a broken arm to orthopedics, serendipitously located right across the hall, and was impressed by how quickly the team fixed the arm and sent him on his way with a sticker and a smile. Soon, she was popping over to orthopedics regularly to peek at interesting cases. She was captivated by the passion and enthusiasm of Mankin and his fellow surgeon-scientists for their work and drawn in by their camaraderie. “It just clicked,” she says.

“I was like, why would I not want to be a physician-scientist?” Chu recalls. “I get the joy of treating patients day to day and the long-term satisfaction of working on unsolved problems through research.”

Chu describes herself as a “bench to bedside” scientist who works on projects with clear clinical applications. Inspired by Mankin’s zeal for cartilage, her early research centered on figuring out how to grow it. She was able to engineer cartilage in the lab, but cartilage repair in patients still did not bring back that pristine joint surface Mankin had shown her. Now, she focuses on preserving the joint surface and preventing other problems that emerge over time after major knee injuries, such as an ACL tear.

Chu explains that while she can reconstruct a patient’s torn ACL to help them in the short term, “that’s not the end of the story.” Within 10 years, many patients develop osteoarthritis as their cartilage breaks down, leaving them with a knee that’s essentially decades older than they are. This is especially common among veterans and athletes who have sustained joint injuries — a population she works with regularly.

“I see too many veterans and athletes cut down in the prime of life by osteoarthritis with chronic pain and mobility issues. These things are difficult to treat, so I’m focusing on prevention,” Chu says.

Chu developed imaging techniques to better detect what she calls “invisible cartilage damage” after an ACL injury. On MRI scans, she says, the cartilage looks completely normal, but it has undergone subtle damage that will ultimately lead to osteoarthritis. “The only way to prevent osteoarthritis is to intervene before it develops, so we need to be able to see those early changes to identify pre-osteoarthritis,” she says. She adds that there aren’t good treatments for osteoarthritis, much less ways to prevent it, which is the focus of her research. She is investigating a range of possible interventions, including gene therapy, physical therapy, regenerative medicine, and anti-inflammatory strategies.

Seeing patients suffer from joint pain she can’t fix evokes pain, empathy, and frustration in Chu — emotions that she channels directly into her research, as she attacks joint problems from multiple angles.

“Service is doing what you can to make the world a better place,” she says. “At this point in my life, my work as a surgeon-scientist is how I can do the most good for the greatest number of people.”

Catherine Caruso is a science writer in the HMS Office of Communications and External Relations.