NIH Funds Protease Research Advancing Understanding of Cancer Progression and Treatments

Lehigh study will visualize activity of proteases, which play a vital role in physiological processes such as tissue development and regeneration and cancer migration and metastasis.

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Amy White

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A project by E. Thomas Pashuck could help researchers understand cancer progression.

A project by E. Thomas Pashuck, assistant professor of bioengineering, could help researchers understand cancer progression (iStock by Getty Images / tonefotografia).

E. Thomas Pashuck, assistant professor of bioengineering at Lehigh, was awarded a National Institutes of Health grant for “Designing Technologies to Visualize Protease Activity in Cancer Models.” Findings could help improve understanding of cancer progression and develop more effective treatments.

Proteases are enzymes that act as catalysts in chemical reactions that break proteins down into peptides and amino acids. They play an important role in many physiological processes, including development and regeneration of tissue and progression of cancer, including migration and metastasis.

Quantifying the activities of proteases within tissues is challenging and current options are limited, said Pashuck, who will use novel biomolecular conjugates that are sensitive to proteases to enable visualization of proteolytic activity in tumors. “We will use confocal microscopy to visualize our model tumors and understand how cancer cells modify their local environment, and also how they modulate the proteolytic activity of other cell types within the tumor,” Pashuck said.

E. Thomas Pashuck

E. Thomas Pashuck, assistant professor of bioengineering is working on a project that could help improve understanding of cancer progression and develop more effective treatments.

While other systems that enable the visualization of protease activity exist, Pashuck’s method was designed to have lower background fluorescence (increasing imaging quality) and enable visualization of multiple proteases at the same time.

Pashuck aims to develop protease-responsive conjugates, incorporate them into hydrogels and visualize spatiotemporal protease activity in model tissue, including hydrogels containing both cancerous and noncancerous cells to better understand metastatic processes.

“This approach is powerful because it can be easily adapted by other labs, can be used for many proteases and incorporated into most biomaterial systems,” Pashuck said in the project summary. “Since proteases catalyze the cleavage of a peptide bond, they are especially useful for making stimuli-responsive therapies. Thus this research can help researchers across disciplines develop more effective biomedical interventions.”

Cancer is the second leading cause of death in the United States and about 40% of people will be diagnosed with cancer at some time in their lives. “Understanding the complex interactions that occur within the tumor microenvironment is crucial for creating more effective therapies to inhibit the processes that lead to poor treatment options,” Pashuck said.

Drugs targeting protease activity have entered clinical trials, but so far have not been successful. New protease therapies that have improved enzyme specificity have been developed. “Increasing our understanding of protease activity in the tumor microenvironment is needed to bring such promising drugs to the clinic,” Pashuck said.

Pashuck, the principal investigator, is working on the project with Lehigh University graduate student Sam Rozans. The total funding amount is $408,493.

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Amy White

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