Brian T. Feeley, MD, FAAOS
Published 3/12/2025
Brian T. Feeley, MD, FAAOS, was bestowed with the 2025 Kappa Delta Elizabeth Winston Lanier Award for his research in advancing the understanding of muscle degeneration in rotator cuff injuries and how it affects repair outcomes. Throughout the past 15 years, Dr. Feeley and his team found the source of fatty infiltration that causes muscle atrophy and leads to poor functional outcomes in rotator cuff repairs. Dr. Feeley is an orthopaedic surgeon, chief of the Division of Sports Medicine and Shoulder Surgery, and director of the Muscle Stem Cell Lab at the University of California, San Francisco (UCSF).
Understanding atrophy pathways
Dr. Feeley and his team—including Xuhui Liu, MD, adjunct professor in the Department of Orthopaedic Surgery at UCSF; Steven Garcia, MD, orthopaedic surgery resident at UCSF; Hubert T. Kim, MD, PhD, FAAOS, vice chair of orthopaedic surgery at UCSF and chief of surgical service at the San Francisco VA Medical Center; and Michael Davies, MD, sports medicine fellow at Hospital for Special Surgery in New York City—developed a mouse model that demonstrated consistent and reproducible muscle atrophy, muscle fibrosis, and fatty infiltration. That mouse model led to the first study showing the regulation of muscle atrophy–related genes in a rotator cuff model of injury, where the team identified a link between a particular molecular pathway—Akt/mTOR—and fatty infiltration. The Akt/mTOR pathway is believed to control protein degradation during muscle atrophy. With this knowledge, the researchers inhibited the development of fatty infiltration with the administration of 1.5 mg/kg of rapamycin daily, which blocked mTOR activity and decreased fatty infiltration for the first time in an animal model of rotator cuff tears.
Identifying cellular source of fatty infiltration
Previous research discovered a mesenchymal cell that had a unique cell surface marker within muscle. These cells allowed researchers to track them over time and how these cells could differentiate into several other cell types with the proper stimulus—the fibroadipoprogenitor cell (FAP). The researchers were able to track the fate of FAPs within muscle over time, finding that after a rotator cuff injury, FAP numbers increased and were located with two fat markers. The team then used a mouse model to knock out or deplete FAPs within muscle. Following rotator cuff injury, a loss of fatty infiltration was seen, confirming FAPs are the cellular source responsible for fatty infiltration.
Although FAPs are responsible for fatty infiltration, other studies showed that FAPs could also be capable of regenerative and pathologic responses to muscle injury. The research team developed a chronic injury where the tendon was injured along with the suprascapular nerve, followed by repair 6 weeks after injury. By testing mouse and human FAPs in vitro with B agonists, the researchers found several outcomes suggesting that FAPs are closer to beige fat, a type of fat cell that burns energy, terming these FAPs beige-FAP. By inducing beige-FAP transplanted cells into a rotator cuff model of injury and after repair with B agonists, the repair group had virtual elimination of fatty infiltration and improved markers of muscle atrophy, demonstrating that pharmacologic stimulation of FAPs could improve muscle function.
Building better tools
The group collaborated with Jarret Weinrich, PhD, assistant adjunct professor in the UCSF Department of Anesthesia and Perioperative Care, to design machine-learning software for pain and kinematic analysis. They can track unbiased motion patterns following rotator cuff injury and repair, mimicking what is seen in a clinical setting.
In a preliminary study, Dr. Feeley and his colleagues discovered that treatment with gabapentin may help sufficiently mitigate pain for rotator cuff patients. The team is currently conducting studies looking at the relationship between spinal cord plasticity and motor function using pharmacotherapies as a treatment strategy to improve outcomes for patients with pain as their primary concern in rotator cuff degeneration.