Disentangling proteolytic networks and evolutionary trends using systems biology


Researchers have recognized that a one-size-fits-all approach is not effective at treating cancer and that tumor heterogeneity plays an important role in response. Hanahan & Weinberg have defined a toolbox, the “Hallmarks of Cancer,” that enumerate some tools of pathogenesis, in which protease dysfunction plays a multitude of roles. Proteases are enzymes that degrade proteins as part of cellular homeostasis. When proteins are aged, defective, or taken up by the cell, these proteins are degraded by enzymes in the lysosomes, such as cysteine cathepsins. In addition to their proteolytic activity inside lysosomes, cathepsins secreted from cells degrade extracellular matrix (ECM). These potent enzymes are up-regulated in tissue-destructive diseases such as cancer; however, researchers have not been successful in alleviating cathepsin dysfunction. This research develops a mechanistic understanding of how cathepsins interact with ECM and each other through mathematical modelling, mutant-protease experiments, and biological machines application. Additionally, this integrated systems biology approach used to explore proteolysis was then harnessed for developing a computational framework to quantify tumor heterogeneity across a leukemia cohort for patient stratification and personalized medicine.

Gainesville, Florida, USA

UF BME Seminar Series