A Pioneer in Biomedical Engineering: Deborah Leckband

A Pioneer in Biomedical Engineering: Deborah Leckband

The enthusiasm professor Deborah Leckband feels for her research is undeniable. Understandably so, because her group has been breaking new ground in biomedical engineering for decades. Her recent work uses an unconventional approach to address the difficult problem of stabilizing therapeutic proteins in drug carriers. 

From Chemistry to Chemical Engineering

The road to her current research began during her graduate studies in chemistry at Cornell University, where Leckband became very interested in biotechnology and the exciting new opportunities for research.

“I was doing a lot of … basic biophysical chemistry research at Cornell, but what I was really excited about were the developments in biological engineering that was going on in chemical engineering,” Leckband said.

To pursue this interest, Leckband joined Robert Langer's lab at the Massachusetts Institute of Technology as a postdoctoral researcher. Together, they worked on a blood filter that used immobilized enzymes to remove heparin after surgery. While Langer focused on the filter's design, Leckband became particularly interested in how the materials used for blood filters influenced their biocompatibility.

“Cells and proteins in the body react to the surfaces of the materials that you're using for these for these kinds of devices,” Leckband explained. “A lot of polymers used for blood filters or for catheters tend to cause coagulation and can also promote an immune reaction. It really comes down to the surface properties of the material – how biology sees that material and how it responds. And what I saw was a huge unmet need to really understand on a fundamental level what was happening at that biology-material interface."

Leckband pursued this question by continuing post-doctoral research with Jacob Israelachvili at the University of California, Santa Barbara. There, she utilized advanced instrumentation to study the surface properties of biological materials typically used in biotechnology or clinical applications.

“There are many properties that can affect biocompatibility, but the surface properties turn out to be really key,” Leckband said. “So this is an exciting area, because it’s surface science but you’re applying it to clinical and biological problems.”

Using the instrumentation developed in Israelachvili’s lab, Leckband studied polymers used for clinical or biotechnology applications, focusing on how their molecular scale surface properties influence interactions with cells and proteins. At the same time, she began exploring biological materials like lipids, proteins and carbohydrates to understand the “biological design roles” that could be exploited to make biomimetic materials, which have properties similar to naturally occurring materials like cell membranes.

Engineering Materials Fit for Proteins

More recently, Leckband has been developing a new way to look at how materials affect the function and stability of encapsulated proteins, as used in drug delivery.

“A lot of our drugs now are proteins, like antibodies. You don’t want to inject protein straight into the body because it gets cleared quickly” she said.

Instead, proteins are often encapsulated into a polymetric matrix that shields them from the biological environment. However, synthetic materials can destabilize proteins, causing them to unfold or denature.

“The challenge is that you’re losing the function of these high value proteins – if 60 percent of your protein is denatured, that’s 60 percent of your drug that is just destroyed or compromised as a consequence of putting it into this artificial matrix,” Leckband said.

In collaboration with chemistry professor Martin Gruebele, Leckband is using fast relaxation imaging to study protein stability within the polymer carriers. This technique uses fluorescence to monitor proteins and an infrared laser to apply small thermal pulses, inducing protein unfolding. By analyzing the way the protein responds to the thermal pulse, they can evaluate how the environment affects the protein stability within the material.
The knowledge they are gaining with this approach could revolutionize drug delivery systems, for example, by guiding the design of carriers that preserve protein function until they reach their target.

“The reason why I think it's kind of cool is that it's a nice blend of several concepts of chemical engineering,” Leckband said. “It's thermodynamics. It's kinetics. It's also using catalysis and material science.”

Her research has also revealed that the mechanical properties significantly influence biological responses to materials. Since joining the chemical and biomolecular engineering department at the University of Illinois Urbana-Champaign, her team spent several years exploring mechanotransduction – how cells read that mechanical information and convert it into biochemical responses.

One project examined ventilator-induced lung injuries, where mechanical forces associated with artificial ventilation can trigger biochemical changes that disrupt tight capillary junctions, causing fluid leakage into the lungs and acute respiratory distress. Her group also collaborates with Illinois colleague Joon Kong, Robert W. Schaefer Professor in ChBE. Her recent National Science Foundation grant with bioengineering professor Susan Leggett is exploring mechanotransduction in tumor metastasis and developmental biology.

A Transformative Career

This current thrust of her research is just the latest in her long research career, most of which has been done during her tenure at Illinois, and which has evolved hand-in-hand with the department itself. Since joining the faculty in 1995, Leckband has witnessed remarkable growth in the department.

“[When I started], we had a small number of faculty and very few bio people,” she said. “Since then, the department has gone through a whole transformation in terms of the breadth of research, and also the number of new faculty. It’s really an exciting place, and it has been fun to see the department undergo all these changes.”

Leckband is helping usher in even more growth in her concurrent role as Associate Head for Development. She often travels with the Advancement team to connect with alumni and share about the department’s priorities: modernizing its facilities, delivering a world-class educational experience and fostering groundbreaking research. During these conversations, Leckband – who served as Department Head from 2003-2005 – provides important context about the department’s strategic goals and how alumni support can help achieve that vision.

“There's a point where you can see them – it's almost a transformation – when the lights go on and they really understand the science.”

“One of the things I really love about going out and meeting alumni is hearing all the exciting things that they are doing and also hearing about what a positive experience they had when they were in chemical engineering,” she said. “Hopefully, alumni will continue to support the department so we can keep doing the good things we’ve been doing.”

Above all, Leckband treasures her role as an educator. She notes that over the years she has published countless papers, collaborated with many researchers, and consulted often with industry, but the "product” of which she is most proud is her students.

“There's a point where you can see them – it's almost a transformation – when the lights go on and they really understand the science, but also understand that they are capable of carrying this forward on their own and they don't need me all the time,” she said. “You can see that maturation, and it is one of the most gratifying things. Those are my happy days.”