Tumor resistance to cytotoxic agents is a major cause of cancer therapy failure and bacterial resistance to antibiotics is a growing problem worldwide. We are in a set of projects trying to identify early molecular events that we can associate either with a functional- or a non-functional response to a drug.
We have generated leukemic cell lines which either are progressively more resistant, or selected from a drug sensitive population as being inherently resistant to the drug. Bacterial models are developed in a similar fashion. By subjecting sensitive/resistant cells to drug treatment, we are seeking to identify specific pathways that are changing in a functional/non-functional response to drugs. Metabolic alterations leads us to hypothesize around specific proteins with which we subsequently proceed to evaluate using western blotting, siRNA knock outs, over expressing cell lines. Ultimately we seek to identify molecular targets towards which new drugs could be developed.