Cellular fate is controlled by multiple molecular pathways. The best studied is apoptosis, a form of programmed cell death used by all multicellular organisms to eliminate cells that are damaged, no longer needed or which might become a threat to the organism. This process is often deregulated in cancer cells allowing them to survive and proliferate when otherwise they should be eliminated.
Dysfunctional apoptosis can cause or accelerate cancer development, but also underlies resistance to common cancer treatment approaches such as chemotherapy. Members of the Bcl-2 family of proteins are critical regulators of apoptosis with some members promoting cell survival and others promoting cell death. Recently, a new class of drugs called “BH3 mimetics” have been developed to target some Bcl-2 pro-survival proteins, and these are showing significant promise in clinical trials for the treatment of cancers such as leukemia and lymphoma.
Our ultimate goal is to develop drugs that will be used to treat cancer patients. Complementary projects in the lab focus on autophagy, a cell survival process that has significant cross-talk with apoptosis. Similar approaches will be used to understand the molecular details of authophagy regulation, how it influences apoptosis, and its role in cancer development and treatment.