Xiaodong Wang

The goal of our research is to understand how and why our cells die through apoptosis and eventually use this knowledge to combat human diseases in which apoptosis becomes defective. These diseases include cancer and neurodegerative diseases during which apoptosis is either blocked or undesirably turned on. We have been using biochemical approaches to study apoptosis. Specifically, we set-up biochemical assays that reproduce biochemical reactions that contribute to apoptotic cell death. Using this approach, we have uncovered biochemical pathways that activate intracellular apoptotic proteases (caspases) and fragment chromatin DNA during apoptosis. During the biochemical analysis of apoptotic pathways in human cells, we discovered the role of mitochondria in apoptosis. We found that mitochondria release proteins such as cytochrome c, Smac, and EndoG from their intermembrane space during apoptosis. These proteins then interact with cytosolic proteins to trigger the activation of caspases and DNA fragmentation. We also found that the release of these apoptogenetic proteins is regulated by the Bcl-2 family of proteins, a group of homologous proteins that have roles in tumorgenesis. Our current research is focusing on how apoptotic signals transduce to mitochondria. We are also collaborating with chemists to design small chemicals to regulate the mitochondria-initiated apoptotic pathways.