Overview

A critical step in tumor development is the invasion of surrounding tissues, a process that can lead to development of distant metastases. Tumors accomplish this through increased activity of enzymes that degrade the proteins connecting the cancer cells to each other as well as the structural elements of the extracellular matrix. In the microenvironment of normal tissues, proteolytic activity is modulated by endogenous inhibitors that bind to and inactivate proteinases; in malignant tumors, the delicate balance between production, activation, and inhibition of proteinases is often disturbed, leading to tumor cell invasion and dissemination.

Different forms of cancer show increased activity of specific proteinases and decreased activity of the opposing endogenous inhibitors; identification of these altered interactions provides a handle for therapeutic intervention. Through studying the natural interactions between these enzymes and their endogenous inhibitors, we hope to design better agents for blocking tumor invasion and metastasis. My laboratory is investigating proteinases implicated in several types of cancer. Our research focuses on the molecular interactions involved in inhibiting these proteinases, employing techniques of structural biology, cell biology, and enzymology.