(Tom Barker, left, Shayn Peirce-Cottler, center and Dr. Catherine Bonham)

The cells in your body are big talkers. They use chemical signals to coordinate and complete tasks that no single cell can carry out on its own — from building a muscle to making tissue for bones. When a cell wants to dial up its neighbor or make the molecular equivalent of a long-distance call, it generates and secretes specific proteins and other molecules that other cells can receive and understand. Together, the cells orchestrate building and maintaining the many intricate parts of the human body. 

But what happens when the communication breaks down?

One disease thought to result from a cell communication problem is idiopathic pulmonary fibrosis, or IPF, a chronic illness where cells somehow get the message to produce masses of scar tissue — a type of fibrosis — that build up in the lungs and eventually stop lungs from transporting oxygen into the bloodstream effectively.

With no known cure and only a pair of drug treatments that can at best slow progression, fibrosis cells multiply unchecked until the lack of oxygen causes respiratory failure or another fatal illness. According to the American Association for Respiratory Care, IPF is nearly always fatal and affects about 128,000 people in the United States. About 48,000 new cases are diagnosed each year, and about 40,000 deaths are recorded.

But there’s hope on the horizon. University of Virginia biomedical engineering professor Shayn Peirce-Cottler has teamed up with other UVA researchers to learn about cell communication and IPF and how to work toward identifying the reasons IPF develops. Early work has been promising. 

“We are trying to treat disease by examining cell communication,” Peirce-Cottler said. “With this approach, we think we can better understand and then control the intercellular conversation. We want to stop or change the message that tells healthy cells to turn into disease cells.”

Peirce-Cottler’s research focus area in the School of Engineering and Applied Science is the microvascular system — the blood vessel network in our bodies. In addition to using her biomedical background, Peirce-Cottler integrates advanced modeling and experimental techniques she has developed over her career. This approach has been key to making headway on the extremely challenging task of tracking down details about how cell communication works.

Toward this effort, Peirce-Cottler has joined forces with Dr. Catherine Bonham, who specializes in lung immunology in the Division of Pulmonary and Critical Care Medicine at the UVA School of Medicine, and Tom Barker, who specializes in fibrosis in the biomedical engineering department.

The team members recently received $2.2 million from the National Institutes of Health to support the continuation of their important work, which was initially supported by a seed grant from the UVA Center for Engineering in Medicine.

“We have fantastic preliminary data from our pilot project,” Peirce-Cottler said. “We think this data points to the cells responsible for the proliferation of fibrosis cells. We are very hopeful that, with this knowledge and further research about how to give these cells a different message, we may be able to halt the progression of IPF.”

In their pilot project, team members discovered that cells in the vascular system, called microvascular pericytes, could be turning into fibrosis-generating cells, called myofibroblasts. Their research linked the possibility of both the immune system and the microvascular system being involved in fibrosis development.

“This is big,” Bonham said. “The vascular and immunology research areas traditionally haven’t crossed borders, but now collaboration between these two medical fields has enabled the discovery of a possible interface between body systems. We may have uncovered the codes used, in the form of molecular signals, between these systems and identified a contributing factor to IPF.

“Pinning down all the different things going on in these systems is very complex,” she said. “It’s not something we can understand in a dish.”

Not all pericytes turn into dangerous fibrosis cells. So the question is: What are the circumstances and signals, or lack of signals, that create a myofibroblast?

To study the many components of cell behavior, the team is using agent-based computational modeling together with data science and lab experiments to study how and when cell communication gets disrupted and fibrosis forms.

In this approach, which crunches through huge amounts of data, researchers can simulate myriad experiments and outcomes on a computer and discover patterns more quickly than if these experiments were conducted in a lab. These patterns inform the most promising avenues of study and help indicate which computer model experiments should be confirmed in a lab setting.

The goal is not only to analyze what’s happened but develop a predictive tool for maintaining healthy cell communication.

“What makes this next research phase so exciting is that we are not only going to look at the how and when of fibrosis development, we are going to start looking at the where,” Barker said. “We’ll look at different areas of the lung to see what happens with different combinations of cell types and cell subtypes — and where things go awry.

“At a cellular level, the lung is pretty big and it’s very complicated architecturally,” he said. “The agent-based modeling hopefully will allow us to get that spatial information and allow us to make spatial predictions, too.”

“In a tissue outside the lung, the group has shown that pericyte-to-myofibroblast differentiation is preventable and reversible, Peirce-Cottler said.

“This is unbelievably promising,” she said. “The whole team is excited about the next part of our research.”