In the first project we are studying the mechanisms by which Bcl-2 family members prevent cell death that would normally be caused by chemotherapy agents. Our recent data indicate an unexpected role for Bcl-2 in regulating cell adhesion. This function of Bcl-2 may explain why in some cancers expression of Bcl-2 is an indicator of a good prognosis even though it makes that cell type resistant to chemotherapy drugs. The hypothesis that we are testing is that by upregulating adhesion Bcl-2 downregulates metastasis.

In the second project we are developing a brand new method for in vitro evolution and selection of peptides with novel functions. This technique called covalent display is sort of like phage display without phage or a yeast two-hybrid system that does not use yeast! We are using this system to evolve specific inhibitors for individual Bcl-2 family proteins from the BH3 domain of Bak.