Professor wins grant to study the body's ability to heal, regenerate

Connor Dolan, an assistant professor in the School of Life Sciences, has received a five-year National Institutes of Health R01 grant for his project, “Understanding the Role of Mechanical Load in Endogenous and Induced Mammalian Digit Regeneration.”

Dolan’s work centers on a remarkable biological ability: In mammals, including humans, amputations at the fingertip can naturally regrow bone, nerves, blood vessels and connective tissue. By contrast, amputations at other points on the limb require prosthetics or surgical reconstruction.

“What we do in our lab is try to understand how a part of the appendage can regenerate without any sort of intervention and then take what we learn from that and apply it to nonregenerative injuries,” Dolan said.

A few years ago, it was discovered that regeneration is “load dependent.” Mechanical load, Dolan explained, “is the internal and external forces that your body and cells experience during exercise, cell migration, and everything in between."

Using examples from astronauts in zero gravity to tennis players with stronger racket arms, Dolan described how such forces shape bone and muscle strength and, in his team’s findings, also influence regeneration.

This NIH-funded project focuses on a protein called Piezo1, which “detects mechanical load.” By activating or inhibiting Piezo1, researchers can mimic conditions like exercise or spaceflight. “Because we know that regeneration is load dependent,” Dolan said, “this grant is largely about the role of this protein Piezo1 and how it detects mechanical load.”

Part of the project will explore a synthetic molecule called Yoda1, which Dolan described as “a door jam for Piezo1” that can simulate mechanical load in cells. His team will test whether combining this type of simulated loading with pro-regenerative molecules like BMP2 or BMP9 can enhance repair — an approach known as “regenerative rehabilitation.”

“This concept is about combining traditional pharmaceutical treatments to initiate a response while concurrently using the principles of physical therapy to synergize the both of them,” he said.

The lab uses Arizona’s only in vivo high-resolution micro-CT scanner to track digit regeneration in real time. Students are deeply involved, from image analysis to histological work.

“The student response has been fantastic,” Dolan said. He credited undergraduate assistants for making significant contributions.

Dolan’s first PhD student, Alison Ingraldi, will join the lab this month and "be heavily involved" with the NIH project.

Dolan’s interest in regeneration began as an undergraduate at Tulane University, where he worked in the lab of a scientist he calls “the founder of this field.” Mammalian regeneration research, he noted, is small, with “probably around 10 labs across the world studying this right now,” but growing in attention and funding.

Reflecting on his first year at ASU, Dolan said, “This first year has been terrific. I’m so glad that we made the decision to come here. … Everyone has been so supportive, at every single level, which is really wonderful.”