Research Concentration - Biology of Cellular Stress
College of Arts and Sciences
|CLS, Room 505
Our research focuses on regulation of cell survival and apoptosis by interferon-induced, double-stranded RNA activated protein kinase PKR. In particular, we study the regulation of PKR’s kinase activity by its activator protein PACT (DYT16) in response to stress signals that include oxidative stress, growth factor withdrawal, and endoplasmic reticulum (ER) stress. Our work has major implications on origin, progression, and treatment of many human diseases and disorders such as cancer, neurodegeneration, diabetes, and aging.
Stress signals lead to an increased association of PACT with PKR that causes PKR to become enzymatically active and phosphorylate protein synthesis initiation factor eIF2 alpha. This leads to a general block in protein synthesis and since the amounts of eIF2 alpha in the cell are limiting, even minor changes in eIF2 alpha phosphorylation lead to a significant inhibition of protein synthesis.
We are interested in mechanistic questions that address regulation of cell fate (survival or apoptosis) in response to stress signals. The lab focuses on protein-protein interactions and we use many biochemical and genetic assays to determine how interactions between proteins change in response to environment, primarily by changes in protein modifications such as phosphorylation.
Point mutations in PACT have been shown to lead to early onset, generalized dystonia. We are working towards understanding if the identified substitution mutations in PACT that lead to dystonia change the cellular response to stress and alter the cellular outcome in terms of survival and apoptosis.
In addition to this, in collaboration with the Dudycha lab, we are currently investigating stress response and its effects on aging and longevity using the microcrustacean Daphnia as a model system. We focus on heat shock response, eIF2 alpha phosphorylation, and its relationship to life span determination.