Dr. Stephen T. Smale's research examines how stimuli alter gene expression. He hopes to pinpoint how and why certain inflammatory stimuli activate or inhibit the expression programs of inducible genes in immune system cells. Using genome-wide approaches, his lab strives to understand selective transcriptional responses to different stimuli and to delineate the mechanisms of the transcriptional cascade.
"It’s really not random evolution; there must be a logic that has important implications both mechanistically and biologically," says Dr. Smale.
Dr. Smale believes understanding the cascades driving gene expression will help us achieve the deep mechanistic understanding of immune-related diseases necessary to develop more effective treatments.
In the past, research on transcriptional regulation focused on individual model genes, which researchers hoped would produce insights relevant to a broad pool of related genes. However, the model gene approach failed to explain the great diversity of gene regulation strategies required in a complex, multicellular organism, or the logic underlying that diversity.
Recent developments in the ability to analyze gene expression and gene regulation mechanisms at a whole-genome scale allowed Dr. Smale to start building a deeper understanding of the transcriptional process's overall mechanistic and biological logic.
By taking a systems approach to studies of the transcriptional cascades, Dr. Smale has pinpointed many molecular mechanisms that induce or repress gene expression in immune cells.
Read more about his findings in the following publications:
Even though the field remains in its infancy, Dr. Smale has high hopes for how budding technologies will help researchers achieve unprecedented insights into the logic of the transcriptional process. Techniques such as RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), ATAC-sequencing (ATAC-seq), CRISPR, and chromatin conformation capture, along with an emerging suite of single-cell methods, all help researchers get closer to a complete understanding of gene expression in immune system cells.
A major hope for the future is for researchers in the field to use the knowledge gained from a deep understanding of gene regulation mechanisms to develop strategies that allow the selective modulation of gene expression for the treatment of diseases linked to inflammation and the immune system.