Bitter Side of Sweet: Professor Explores How Cells’ Sugary Coat Influences Health, Disease Formation
Matthew Paszek, a new professor of biomedical engineering at the University of California, Davis, is fascinated by sugar. No, not the sugar in a can of soda or a chocolate bar, but the sugar coating every living cell in the human body.
Paszek researches at the forefront of glycoscience, a developing field that explores the structure and function of glycan. Known as the third chain of life, just after nucleic acid and protein, glycan is an essential molecule made up of sugars bonded together. It appears on the outer layer of cells, in proteins and antibodies, and even in viruses.
Paszek has significantly propelled the field of glycoscience forward by being the first to describe the physics of glycans, particularly at the nanoscale. Through this research, he has shown that glycan is a major contributor to the development of aggressive forms of cancer.
However, the mechanisms by which glycans influence cancer and other diseases are still poorly understood. This is due to the wide range of shapes and sizes the sugary molecules can take. The field needs the development of genetic tools, imaging methodologies and conceptual frameworks, enabling researchers to pursue next-level insights.
This is exactly what Paszek and his lab aim to accomplish: Help create and define the tools and techniques of glycoscience to establish it as a coherent subdiscipline of the biosciences and biomedical engineering. At the same time, Paszek works to translate his team’s foundational work into technologies and therapies that improve human health.
"We've taken what we have learned in our cancer research [with glycans] and applied it to develop new biotechnology, often for applications unrelated to cancer," Paszek said.
The Many Sides of Sweet
Paszek’s glycoscience research falls under four categories: glycocalyx engineering, mucin biotechnology, biophysical glycoscience and molecular imaging.
Glycocalyx (literally, “sweet husk”) engineering focuses on manipulating the sugary outer layer found on cells to hack their chemical and physical structure. Paszek’s team uses tools like CRISPR to build new DNA instruction sets for the glycocalyx, allowing new material states to be observed and tested.
Mucin biotechnology is where Paszek and his lab translate the discoveries from glycocalyx engineering into devices and technologies for improving human health. Mucins are large, sugar-coated proteins providing lubrication and protection from disease.
An example of Paszek’s work with mucins is his engineered lubricin, a lubricant important for hydrating and protecting biological surfaces. The engineered material has the potential to treat conditions such as dry eye disease and osteoarthritis.
Biophysical glycoscience investigates the physical principles of glycan; for Paszek’s lab, this means exploring how the glycocalyx packages, sends and receives biomolecular signals.
Paszek’s work in molecular imaging revolves around innovating ultra-precise imaging techniques for the advancement of glycoscience, such as the Scanning Angle Interference Microscopy technique he developed, which allows researchers to map the thickness of the glycocalyx.
“Manipulation and observation are fundamental to science, but we've been limited in our ability to do either at the tiny nanoscopic scale where we believe some of the most intriguing biology unfolds. We are working to overcome these limitations and have made some exciting progress," Paszek said.
Chain of Events
In 2014, Paszek joined Cornell University as an assistant professor in the School of Chemical and Biomolecular Engineering. Paszek would stay to become an associate professor and director of graduate studies in the school before accepting his new role as professor of biomedical engineering at UC Davis in 2025.
"UC Davis is a great place for biomedical engineering due to its excellent research infrastructure and collaborative opportunities across engineering, medicine and the biological sciences,” Paszek said. “These opportunities include partnering with UC Davis' world-renowned School of Veterinary Medicine and researchers throughout the Bay Area."
Paszek earned his Ph.D. in bioengineering at the University of Pennsylvania and his Bachelor of Science degree in chemical engineering from Cornell University.