While other systems that enable the visualization of protease activity exist, Pashucks 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.

Link:
NIH Funds Protease Research Advancing Understanding of Cancer Progression and Treatments - Lehigh University News