Brian T. Feeley, FAAOS, Receives Kappa Delta Elizabeth Winston Lanier Award

Brian T. Feeley, MD, FAAOS, has received the 2025 Kappa Delta Elizabeth Winston Lanier Award from the AAOS for his research in advancing the understanding of muscle degeneration in rotator cuff injuries and how it affects repair outcomes. This award recognizes research in musculoskeletal disease or injury with the potential to advance patient care.

Over the last 15 years, Dr. Feeley and his team found the source of fatty infiltration, which causes muscle atrophy and leads to poor functional outcomes in rotator cuff repairs.

“Our central premise was that fatty infiltration fundamentally is an intramuscular cellular problem in which something within the muscle was turning into fat,” said Dr. Feeley, orthopedic surgeon, chief, Division of Sports Medicine and Shoulder Surgery, and director, Muscle Stem Cell Lab at the University of California San Francisco (UCSF). “We didn’t think fat would infiltrate the muscle, as it is inherently lazy. The second premise was that there has to be a reason that fatty infiltration is occurring. If that is true, fat is normally a store for energy, so maybe the muscle is storing energy for possible regeneration.”

Dr. Feeley and his team developed a mouse model that demonstrated consistent and reproducible muscle atrophy, muscle fibrosis, and fatty infiltration, allowing researchers an animal model that could study pathophysiologic changes that occur in rotator cuff tears. The mice model was used because mice could use their rotator cuffs similarly to humans. 

The team included Xuhui Liu, MD, adjunct professor in the Department of Orthopedic Surgery at UCSF; Steven Garcia, MD, orthopaedic surgery resident PGY5 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, Hospital for Special Surgery in New York City.

About the Research

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 in the rotator cuff model. 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 (an immunosuppressive drug) daily, which blocked mTOR activity and decreased fatty infiltration for the first time in an animal model of rotator cuff tears.

Dr. Feeley aimed to understand if FAPs were the cellular source of fatty infiltration in the mouse models of rotator cuff tears. 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.

The research team set out to determine if FAPs could show regenerative traits when given the right conditions, potentially acting as a hidden source of stem cells in muscles that could be activated to help repair muscle tissue.

Using single cell RNA sequencing, Dr. Feeley and his team are currently studying how FAPs can play a role in regenerative strategies in rotator cuff injuries. Treating FAPs with B-agonists and performing single cell RNA sequencing found two key pathways hold promise for muscle regeneration. Six distinct subpopulations of human FAPs were found to have the presence of a fat cell that generates heat by dissipating energy and extracellular vesicle-associated markers.

“We’ve shown in mice that it would be a reasonable next step to look at a pharmacologic treatment in a large animal model and then proceed to a clinical trial, which could be feasible in the next three to five years,” said Dr. Feeley. “Some of our recent studies have looked at not only if a pharmacologic treatment works but the mechanisms behind that. We’ve studied different potential avenues based on our single-cell data ― FAPs treated with a B-agonist or a drug stimulant that seem to secrete EVs that promote muscle regeneration, which is specific to those cells. We can imagine a treatment where you bank the B-agonist-treated FAPs and administer them directly into the muscle at the time of surgery to promote muscle regeneration.”

To capture pain and kinematic movement data in an unbiased manner following rotator cuff repair, the group formed a collaboration 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.

In a preliminary study, Dr. Feeley and his colleagues discovered that treatment with gabapentin (a neuropathic pain medication) may help 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.

“One of the drivers of better outcomes is how well the muscle functions after surgery. So, for practicing clinicians, it is important to understand the mechanisms behind how our muscles work and the generalizability of all basic science studies, whether you are a shoulder or spine surgeon,” said Dr. Feeley. “We already know we can do great hip and knee replacements, but the variability in patient outcomes is pretty large. Shoulder surgeons are a bit ahead of other specialists because we understand how muscle quality affects not only rotator cuff injuries, but also the pull of the shoulder. This, in turn, impacts clinical outcomes for patients.”