Gene expression describes how the genetic information in DNA produces the proteins that perform most cellular functions. The instructions for producing a protein are carried from the DNA to the protein synthesis machinery by a molecule called messenger RNA (mRNA). Furthermore, in a cell, mRNA is coated with a number of different proteins. The composition of the proteins on an mRNA is dynamic, and these changes determine the extent to which the protein encoded by the mRNA is produced.

Alterations in gene expression are crucial in many diseases such as cancer, viral infection, developmental disorders, aging, and others. Much gene expression research has focused on transcription, an early step of expression, but it is becoming increasingly clear that other gene expression processes are also involved in disease, including protein synthesis, also known as translation.

A family of enzymes, called DEAD-box RNA helicases, are involved in many steps of gene expression and are critical for changes in the mRNA-protein composition. A DEAD-box enzyme called Ded1 in yeast cells is known to be critical for protein translation. The version in humans, called DDX3, has been linked to cancer, especially medulloblastoma, a type of brain cancer. DDX3 is also involved in infection by several viruses, including hepatitis and HIV.

Currently, research in our laboratory is primarily focused on understanding how Ded1 affects translation and how its activity is controlled. We primarily utilize yeast cells in the lab, which allows us to take advantage of techniques that are difficult or impossible in human cells. The gene expression machinery is highly similar in yeast and humans, so discoveries made in yeast should be directly applicable to human biology. This part of our research explores some of the basic mechanisms of cell biology. It is imperative to understand how a protein or cellular process works normally before its role in diseases can be determined. We are also working on a project to examine the differences between normal Ded1/DDX3 and the mutant versions found in cancer. Clinical research today depends upon many earlier discoveries in basic cell biology, such as the seminal work in cell cycle control (done in yeast) that has yielded a number of avenues for cancer therapies. We suggest that our studies may likewise prove to be an important foundation for clinical work in the future.