BME PhD Thesis Proposal Presentation

Date and Time: Thursday, February 23rd, 4pm

Location: MoSE 1201A

Committee: Manu Platt (advisor)

Melissa Kemp

Christine Payne

Eberhard Voit

Shelly Peyton (UMass Amherst)

Title: Mathematical modeling of tumor associated macrophage protease activity in breast cancer

Abstract: Tumor associated macrophages (TAMs) promote tumor growth, angiogenesis and metastasis and can make up 50% of tumor mass in late-stage metastatic breast cancer. TAMs contribute to tumor progression through the release of inflammatory chemokines, growth factors and proteolytic enzymes including the cysteine cathepsins B, L, K, S and V. Cathepsins are potent catalysts of extracellular matrix (ECM) degradation, but have also been identified as regulators of cellular process that operate through the activation of signaling pathways and the cleavage of transmembrane receptor proteins, chemokines, and cellular adhesion molecules. Cysteine cathepsins are components of a complicated regulatory proteolytic network, which includes multiple biochemical and biomechanical stimuli, endogenous protease inhibitors and other proteases capable of activating or degrading other proteases. Development of a computational model system of the cathepsin proteolytic network, which includes intracellular feedback loops and extracellular matrix degradation by proteases secreted by tumor cells and macrophages, would expand knowledge on the coordination and complex interactions of macrophages and cancer cells and be a useful tool for developing and testing pharmaceutical cathepsin inhibitors in the future.