Associate Professor of Biology Ryan Petrie, PhD, was awarded a five-year, $2 million grant from the National Institutes of Health (NIH) to further his research on the molecular mechanisms that human cells use to move through the diverse three-dimensional tissue environments in the body.  

This fundamental cell behavior is crucial for a wide range of biological processes in both health and disease. While the movement of cells through three-dimensional tissue is essential for physiological processes like wound healing, it is also a lethal characteristic of metastatic tumor cells.  

The goal of Petrie’s research is to understand how cell behavior and architecture is reprogrammed in response to the structure of the material the cells move through. This information could aid in the development of new therapeutic strategies to control the movement of normal and abnormal cells in the body. 

“Understanding how cells move through structurally diverse 3D matrices will be essential to designing therapies aimed at controlling cell migration in the body,” Petrie explained. “During 3D migration, both metastatic tumor cells and wound healing fibroblasts are faced with the same problem: how to efficiently move the bulky, stiff nucleus.”  

Fibroblasts are the “repair crews of the body,” according to Petrie. They know how to find wounds and generate the scar tissue that is essential to keeping our tissues healthy and functional. But during prolonged disease, they can perform these roles too well, creating scar tissue in otherwise healthy organs causing fibrosis and loss of function.  

“This research seeks to understand the exact molecular mechanisms of how they accomplish both these good and bad outcomes,” Petrie said. “Without this information, developing new therapeutic strategies to promote wound healing and treat fibrotic disease becomes much less likely.” 

To achieve this goal, Petrie’s research will focus on three key gaps in knowledge. 1: how is the nuclear piston pulling mechanism activated in response to the physical environment? 2: How are organelles and endomembranes organized and transported past the nucleus in compartmentalized, pressurized cells using the piston mechanism? 3: Once activated, how is the anterior contractility responsible for pulling the nucleus forward sustained over the hours to days that primary human fibroblasts sustain this mode of 3D migration?  

By addressing these questions, his research will enhance the understanding of the fundamental principles of directional 3D cell motility and migratory plasticity and will lead to new therapeutic strategies to control normal and abnormal cell movement in the body. 

“Advanced medical research exists because of the hard work of generations of scientists to reveal the molecular basis of cell function,” Petrie explained. “The research in my lab shines a light on what would otherwise be a black box, namely human fibroblasts, and the molecular mechanisms we discover have the potential to inspire clinical scientists to take bold, new approaches to treating disease.”  

Faculty members in the College of Arts and Sciences often find synergy between their undergraduate teaching and research, and receiving this grant illustrates how Petrie will combine these efforts. During a previous research grant, Petrie worked with undergraduate student researchers who he says played a critical role in the project's success.  

“I mentor undergraduates to develop intellectual independence and take ownership of their projects. Typically, undergraduates maintain their own human cell cultures, plan their experiments, analyze their results, and keep meticulous records of what they accomplish in the lab,” he described. “While in my lab, they meet with me weekly to discuss their projects, and they participate and present in our group meetings to help them develop communication skills.” 

This type of hands-on research also opens opportunities for students to achieve authorship on peer-reviewed publications, which is a rare achievement for an undergraduate researcher.  

Petrie’s research also leads to opportunities for interdisciplinary collaboration with colleagues across Drexel. “Excitingly, colleagues in the School of Biomedical Engineering, Science and Health Systems and the College of Medicine are working on these same questions but with very different approaches,” he explained. “I expect this funding will allow us to broaden and deepen our collaborations over the next five years.  

“While the benefits to human health remain to be determined, there is no denying that the act of studying this type of fundamental cell biology at Drexel has allowed our students to experience what it takes to make new scientific discoveries in the 21st century.”