Exercise is widely recognized for its ability to improve health and protect against chronic disease. In the Craige Lab at Virginia Tech, researchers are working to understand exactly how that protection develops at the cellular and molecular levels.

Led by Dr. Siobhan Craige, an associate professor in the Department of Human Nutrition, Foods, and Exercise, the lab studies the signals that drive the body’s adaptation to exercise, focusing on exercise-induced changes in metabolism, redox signaling, and communication within and between cells as the body responds to physical stress. 

“When you do an acute bout of exercise, you’re stressing your body out,” Craige said. “Then it must go through this recovery period. In that recovery period, it does all these great things, like increase your metabolism and increase your resilience in multiple different ways.”

Many of exercise's health benefits emerge during the recovery period. In response to the physiological stress of exercise, cells activate signaling pathways that help restore balance, repair tissue, and adapt to the challenge. Over time, repeated cycles of exercise stress and recovery make the body more resilient to future stressors and contribute to protection against chronic disease. The Craige Lab is investigating the molecular signals behind those changes, including reactive oxygen and nitrogen species that can act as messengers between cells. 

One of the lab’s central questions is how the different cell types within the skeletal muscle communicate in response to exercise. Skeletal muscle contains more than muscle cells alone. It also includes endothelial cells, which line blood vessels, along with several other cell types that contribute to the body’s response and recovery.

To determine how these cells “talk” to each other in response to exercise, the Craige Lab uses specialized genetic models to track responses in specific cell types. The work generates large-scale datasets, including RNA sequencing data that provide insight into how gene expression changes across tissues and cell populations following exercise. To transform these complex datasets into meaningful biological findings, Craige and her doctoral student, Rebecca Wall, partnered with Dr. Xuemei “Missi” Zhang, a Research Scientist at Virginia Tech’s Center for Biostatistics and Health Data Science (CBHDS). 

Zhang’s work integrates biological knowledge with expertise in bioinformatics, applied statistics, and machine learning. CBHDS provides bioinformatics support to help researchers develop customized, rigorous, and reproducible approaches for analyzing complex omics datasets.

Craige said that CBHDS’s expertise has been essential to advancing the lab’s research. 

Getting these large and complex datasets analyzed is one thing; being able to explore the data themselves gives researchers the freedom to revisit the analyses, try different approaches and pursue new questions as they arise.

“I don’t know how we would have analyzed these (large and complex) datasets ourselves,” Craige said. “Having the flexibility to do your own analyses, switch parameters, look at it again and look at it from different perspectives is absolutely fundamental to really getting a good idea of what’s going on.”

Rather than simply receiving completed analyses, Wall has worked closely with Zhang to learn the process from the ground up. During weekly meetings, Zhang has guided her through preparing raw sequencing files, using Virginia Tech’s Advanced Research Computing (ARC) resources, conducting quality-control checks, aligning sequencing reads to the mouse genome and identifying changes in gene expression.

Zhang writes and explains the code, while Wall runs the analyses, investigates errors and learns how each decision affects the results. 

“Missi has been walking alongside me through everything,” Wall said. “I’ve been able to actually take more ownership in the data because now I can see if a sample is bad, why it is bad, how it is bad and whether it makes sense.”

Before beginning the collaboration, Wall was familiar with R, RStudio, but had not worked extensively with the workflows required to analyze large-scale sequencing datasets. Learning these approaches has changed how she views quantitative analysis.

“I used to think you had to use biostatistics to show your data, and that was kind of it,” Wall said. “Now it has opened up a whole world. It’s involved in everything we do, and it’s so impactful in how you represent your data.”

The collaboration also demonstrates how CBHDS supports scientific training alongside research. By teaching Wall how to understand and conduct the analyses herself, Zhang is helping her develop skills that will continue to shape her work throughout her career. 

“It made this mountain that I had to climb into a hill that I got to climb with other people,” Wall said.

CBHDS has also contributed to the Craige Lab’s broader research efforts, including grant development and projects seeking to integrate RNA sequencing data with metabolic measurements and other functional data. Rather than studying individual datasets in isolation, Craige and Zhang are working to connect molecular changes across tissues with measurable physiological responses to exercise. They are exploring interpretable machine-learning approaches to identify the signals and pathways that may link these responses across biological systems ultimately hoping to predict outcomes.  

For Craige, collaborations like this are becoming increasingly important as biological research generates larger and more interconnected datasets.

“If you really want to integrate all your different readouts and put a conceptual picture together, you need to pair with people from the Center,” Craige said. For Craige, collaborations like this are becoming increasingly important as biological research generates larger and more complex and interconnected datasets.  

By bringing together expertise in exercise biology, molecular science, bioinformatics and mentorship, the partnership is helping the Craige Lab look beyond individual measurements and develop a more complete understanding of how the body responds and adapts to exercise.