‘Puppeteering’ the healing process: How immune system cells orchestrate the mending of broken bones

Ideally, after a bone is injured or fractured, it can grow back together and heal. But in some cases, particularly when the patient has a risk factor such as being a smoker or having diabetes, the bone does not grow back together.

Why this happens — the process behind the broken bones that heal and ones that do not — is at the center of Jefferson Overlin’s research. Overlin, the first student accepted into a new dual M.D.-Ph.D. program in biomedical engineering at Virginia Commonwealth University, is researching the role of immune system cells in the formation of new tissues required for bone fracture healing.

“Successful fracture healing requires the resolution of inflammation and formation of early cartilage that allows the bone to form and bridge the gap between the pieces,” Overlin said.

Overlin recently received a $45,983 grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health to fund his research. The National Research Service Award seeks to enhance the research and clinical training of promising dual-doctoral degree students interested in becoming clinician-scientists.

Overlin, who graduated from VCU in 2015 with a bachelor’s degree in biomedical engineering and a minor in chemistry, is investigating the process by which macrophages — a type of white blood cell that stimulates other immune cells — and a protein macrophages produce regulate stem cells during healing.

“How are they orchestrating the healing process? How are they puppeteering everyone to play their part?” Overlin said. Gaining insight into these questions “will help us understand better how we can manipulate immune cells to improve healing.”

Since 2017, Overlin has worked in the laboratory of René Olivares-Navarrete, D.D.S., Ph.D., an assistant professor in the Department of Biomedical Engineering in the College of Engineering. Overlin’s project is related to Olivares-Navarrete’s study on how the immune system controls the body’s response to medical implants, for which Olivares-Navarrete recently received a $1.76 million NIH grant.

“Jefferson has a very unique understanding of science,” Olivares-Navarrete said. “He sees things from both perspectives: the clinical aspect but also the engineering aspect.”

Overlin is going into his third year of the Ph.D. program. After defending his dissertation, he will spend two more years finishing his medical degree.

“I’d like to work with pediatric patients and pursue a career where I practice medicine and run a research lab,” he said.

“How are they orchestrating the healing process? How are they puppeteering everyone to play their part?” 

Michael Donnenberg, M.D., director of the M.D.-Ph.D. program and a School of Medicine professor, has recently expanded the program to include several new offerings in disciplines outside the School of Medicine and classic basic science.

“The best thing you can do during your M.D.-Ph.D. is get an F30 from the NIH,” he said, referring to the Ruth L. Kirschstein Individual Predoctoral National Research Service Award for dual degree fellowships. “It’s a fantastic honor to already be a funded researcher — Jefferson is the principal investigator on this grant.”

Donnenberg added that the experience of applying — writing your own grant, submitting on deadline, revising if necessary — was also valuable preparation as a scientist and engineer.

“The earlier you get that experience, the better,” he said.

Donnenberg and Olivares-Navarrete said they expect more M.D.-Ph.D. students to pursue a degree in biomedical engineering.

“As technological advances and the biomedical field moves forward, I think biomedical engineering will be a more attractive option for M.D.-Ph.D.s because there is nothing that doctors do in which biomedical engineering is not involved,” Olivares-Navarrete said. “We are involved in every step from diagnosis to treatment.”



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