The regulation of gene expression at the translational level is fundamental for normal cellular homeostasis and survival. Because control of translation is relatively quick and efficient, cells can regulate gene expression quickly in response to environmental stresses. During some cellular stresses such as viral infection, endoplasmic stress, and apoptosis, the cell adapts by inhibiting overall protein synthesis. However, it is apparent that a subset of mRNAs is translated under these conditions. These mRNAs, in general, encode for proteins that are important for the cell to adapt to the environmental stress. The identification of these specialized mRNAs is crucial in our understanding of fundamental gene expression mechanisms and how cells respond to stress and viral infection. The primary areas of the lab are:
A) To examine the mechanisms by which overall protein synthesis is shutoff in response to cellular stress. ER stress and hypoxia are common stresses that occur during the progression of diseases such as cancer and diabetes. By pinpointing the translational control mechanisms underlying these stresses, we will get a better understanding of how cells respond to stress and how these mechanisms may go awry during disease progression.
B) To identify mRNAs that are selectively translated during conditions when overall protein synthesis is shutoff and to elucidate how these specialized mRNAs can bypass the translational control block. Elucidating the translational control mechanisms of these specialized mRNAs is not only important for our overall understanding of gene expression during stress, but may also reveal novel targets for developing therapies against viral infections, stress and cancer.
