St. Jude structural biology department focuses on understanding the molecular breakdowns that lead to disease

When Charalampos “Babis” Kalodimos moved his family to the United States about 20 years ago, a move to Memphis wasn’t in their plan.

Kalodimos was born and raised in Greece and earned degrees in Greece and France before accepting a postdoctoral fellowship in the Netherlands. He came to the U.S. to be a university professor, first at Rutgers University and next at the University of Minnesota Medical School.  

Since 2017, Kalodimos has been the chair of the Department of Structural Biology at St. Jude Children’s Research Hospital® in Memphis.

He fell hard for the St. Jude mission. 

The Department of Structural Biology at St. Jude is working to understand life and disease at the atomic level.

“Structural biology is a collection of technologies that allows us to visualize in exquisite detail the three-dimensional structure of biomolecules, their shape, such as proteins, for example, protein machineries—inside the cell,” Kalodimos said.  

By understanding the components that regulate the function of important biomolecules through the use of sophisticated techniques, researchers are able to gain a clear picture of how molecules look when they function inside a cell.

It’s that information, gained through the deepest of dives inside cells, that allows scientists to understand how a malfunction at the innermost level of a single cell can result in disease. The ability to detect these kinds of vulnerabilities within cells allows doctors and researchers to understand better why the disease developed and to intervene with drugs and other therapeutics, Kalodimos said. 

“And this information enables our scientists to integrate different approaches so we can tackle problems that are very, very challenging,” Kalodimos said.

St. Jude provides researchers with the tools, technologies and necessary resources to address these complex challenges, while working toward the common mission to advance cures for pediatric cancer and other catastrophic life-threatening pediatric diseases. 

In 2019, the Structural Biology Department acquired a nuclear magnetic resonance (NMR) spectrometer, which at that time was the most powerful superconducting magnet in the world.

“It is very similar to the MRI (magnetic resonance imaging) most people are familiar with, only we use much, much stronger magnets,” Kalodimos said. 

Kalodimos’ team collaborates with scientists in other St. Jude departments so that the benefits of biomolecular NMR spectroscopy supports research progress across campus.

“When we open up and welcome the entire community to collaborate, we gain access to a diverse range of biological systems. This, in turn, expands our repertoire, allowing us to explore more biological questions and leverage these tools more effectively.” he said. 

This absence of barriers between departments is important.

Right now, NMR spectroscopy is at the center of an interdisciplinary project by the Department of Structural Biology. This new blue-sky initiative, “Seeing the Invisible in Protein Kinase,” will utilize NMR spectroscopy to detect and characterize rare structural states in protein kinases. 

Protein kinases are enzymes in the human body that are involved in important biological functions, like cell growth. When protein kinases do not function normally and cell growth is uncontrollable, it can lead to cancer, Kalodimos said.

The main goal of the blue-sky initiative is to understand kinases and to use what is learned to develop new selective drugs, he said. 

“We would like to massively increase the number of kinases that we can target and design new drugs (for),” he said.

It’s the kind of work that can be done only at our institution. 

When Kalodimos was contacted by St. Jude officials about his current job, he agreed to visit the campus, but didn’t expect to accept the position. After meeting future colleagues and patients at St. Jude, one visit turned out to be enough.

When he joined St. Jude, there were about 30 people working in the Department of Structural Biology. Today, the department has about 250 people. 

During his first visit to campus, Kalodimos was impressed by the resources made possible by the support of St. Jude donors as well as the spirit of collaboration between medical doctors and scientists.  Those are the same things that have allowed him to attract and keep talent from around the globe.

And although resources help, he said, what locks it in for everyone they’ve brought in is the mission to advance cures and the means to prevent pediatric cancer and other catastrophic diseases. 

At St. Jude, researchers see how their discoveries can translate to help actual patients.

“What seals the deal is their understanding that if they join St. Jude, now they'll become part of a large team with a common mission,” he said. “That’s very important.”