Passion for Athletics, Past Injury Inspire Surgeon’s Research in Regenerative Medicine

Long before Ashley L. Titan, MD, embarked on her medical career and surgical residency, she shared a passion for athletics with her family. Growing up in New York, Dr. Titan often tagged along with loved ones as they frequently participated in triathlons.

“I have been part of triathlons since before I can even remember,” said Dr. Titan, who later became a triathlete herself. “I grew up watching my dad, my mom, my uncle, and close family friends do races.”

Dr. Titan’s enthusiasm for athletics would follow her to Stanford University, CA, where she enrolled as an undergraduate in 2008. Becoming an internationally ranked starter and captain of the Stanford women’s fencing team, Dr. Titan was dealt a major blow in her sophomore year when she tore the triangular fibrocartilage complex of her wrist, which required surgery.

“I had that injury, and I was amazed about what surgery can do,” said Dr. Titan. “It gave me my life back because I was in such excruciating pain.”

It was the recovery process that not only stoked Dr. Titan’s interest in surgery, but also got her thinking about how she could help others dealing with pain stemming from similar injuries. Those experiences would lay the groundwork for her subsequent research interest in tendon-to-bone injuries, which culminated in 2018 when she was awarded an ACS Resident Research Scholarship, funded by the ACS Foundation.

The scholarships provide $30,000 per year for 2 years to residents of a general surgery or a surgical specialty training program. ACS Resident Members with at least 2 postdoctoral years in an accredited American or Canadian surgical training program—of any specialty—can apply.

“Having the opportunity to begin thinking about this question—the question of regenerating the tendon-to-bone interface—was so exciting to me,” she said. “I became fascinated by ligaments and tendons through that injury. I wanted to solve my own problem and prevent it for other individuals.”

The Path to Scholarship

Majoring in philosophy at Stanford, Dr. Titan graduated with honors in 2012 before returning home to New York, where she enrolled in the Mount Sinai School of Medicine (now the Icahn School of Medicine at Mount Sinai). After graduating from Mount Sinai in 2016, Dr. Titan headed back west to Stanford, where she entered the general surgery residency program. Currently, she is a fourth-year plastic surgery resident at Stanford University.

“I love working with my hands, and I really enjoy helping people,” she said about surgery. “It was a way to do both and use my mind at the same time. It’s absolutely fascinating to do something with your hands, and then see an actual change in the patient right then and there.”

It was as a resident that Dr. Titan drew upon the experience of her own injury—as well as her interest, in general, of the tendon-bone interface—to help steer her research.

“It’s a very interesting part of the human body, in that something as soft as muscle is attached to something as hard as bone,” Dr. Titan remarked about the tendon-bone function. “Even when it’s partially torn, it doesn’t ever fully heal, and it’s at a much higher risk of rupture or complete tear.”

Dr. Titan was particularly intrigued by the role that skeletal stem cells (SSCs) play in the process of bone and cartilage repair. Through her work at a laboratory, she found there was an opportunity to do further research in this area.

“We know that SSCs play a role in bone healing and in cartilage, but no one’s ever looked at it in other skeletal sites,” she said. “I did a flow cytometry and discovered there were some SSCs in the tendon itself.”

Undertaking the Research

Prior to Dr. Titan receiving her scholarship, the SSC research field was filled with opportunities for new discoveries. Not only were the cells responsible for tendon-to-bone healing incompletely characterized, but the origins of the cells themselves were unknown.^*

For Dr. Titan, discovering this piece of the puzzle could provide more awareness about how tendons could be better healed, which began with the flow cytometry she undertook in her lab work, and “led to this big project of looking into whether SSCs play a role in tendon-to-bone healing,” she said.

Dr. Titan had been working with plastic surgeon Michael T. Longaker, MD, MBA, FACS, the Deane P. and Louise Mitchell Professor and founder of the Longaker Laboratory at Stanford. Together with Charles K. F. Chan, PhD—who was then a postdoctoral fellow working at the lab—these researchers were the first to identify SSCs in humans and mice.^†

“It was an absolute pleasure to mentor Ashley in my laboratory,” Dr. Longaker said. “Ashley is a very bright and determined trainee who really wants to translate fundamental discoveries into novel clinical therapies.”

Dr. Titan found an ideal mentor in Dr. Longaker, whose research interests include wound repair. “From the very beginning, I was impressed by her organizational skills and mastery of sophisticated scientific techniques,” Dr. Longaker said.

Upon receiving her scholarship, Dr. Titan and a team of other researchers at the Longaker Laboratory investigated whether SSCs can play a role in tendon-to-bone healing. “Without the scholarship, I would not have been able to pursue such an exciting research project,” Dr. Titan said.

Using a supply of laboratory mice as test subjects, Dr. Titan and her team initially increased numbers of SSCs in the enthesis injury to the Achilles tendon-to-bone interface. The team also looked at the role of transforming growth factor beta (TGFβ) in the tendon-to-bone healing process.

By treating the area of injury with a TGFβ inhibitor, the team detected that the number of SSCs increased significantly, which can be a key part of the recovery process. Findings from her research were published in the July 2022 edition of the journal STEM CELLS Translational Medicine.^*

“What was very important was that Dr. Titan discovered a link between the SSCs and the regeneration of tendons,” said Dr. Chan, who is now an assistant professor of surgery at Stanford. “This was not known before.”

Dr. Chan also credits Dr. Titan for developing new assays to test the presence of SSCs postinjury, which could potentially be mobilized to produce new tendon tissue. “This is a really important finding because of the significant clinical burdens associated with tendons,” he said.

Future Research Plans

Ideally, the goal of clinical research is to improve patient care and, historically, many of these discoveries have been supported by awards such as the ACS Resident Research Scholarship.

ACS has funded 213 Resident Research Scholarships since the award was established in 1970.

“Doing basic science projects, getting the mice, and having the opportunity to access all of the amazing laboratories and facilities at Stanford does require a significant amount of funding,” said Dr. Titan. “It would not have been possible without this grant. This grant supported both my ability to do it, and the time to be able to do the research.”

The 2-year Resident Research Scholarship was the first research award Dr. Titan ever received. Since then, she has been awarded a grant by Stanford for transplant and tissue engineering research. Dr. Titan continues to be involved with tendon research, and has delved into research on the postoperative pain experiences of patients.

“The lessons that I’ve learned from these 2 years of this project will be extraordinarily essential and will continue to lend influence further out in my research career,” she said.

Away from her medical and research pursuits, Dr. Titan remains highly involved in athletics, having participated several times since 2011 in the Escape from Alcatraz Triathlon, held in San Francisco. She credits athletics for helping to instill a work-life integration that prevents her from becoming fatigued with her everyday professional responsibilities.

“If I ever get tired or need to think through a problem, I go out for a run to clear my head,” she said. “I need the endorphins to be able to survive. It 100% keeps me going.”

Just as her athletic experiences helped to inform the course of her past medical research, Dr. Titan plans to continue drawing upon athletics as a guide for her future professional endeavors.

“Most injuries only heal 80%, but how do you get to that 100% strength level?” she said. “That’s the billion-dollar question. When I participate in athletics, it’s where I have my greatest ‘Aha!’ moments or think about a really interesting idea that I want to pursue.”

To learn more about the ACS Foundation, its programs, and how to contribute, go to facs.org/acsfoundation.

Kyle Coward is a freelance writer.

^*Titan AL, Davitt M, Foster D, et al. Partial tendon injury at the tendon-to-bone enthesis activates skeletal stem cells. Stem Cells Transl Med. 2022;11(7):715-726. Accessed January 26, 2023.
^†Longaker Laboratory. Profiles. Available at https://www.longakerlab.com/profiles. Accessed January 26, 2023.