The Hahn Laboratory

Welcome to the Hahn Laboratory in the Division of Basic Sciences at the Fred Hutchinson Cancer Research Center in Seattle, WA. Our research focus is the regulation of eukaryotic transcription (the synthesis of RNA using a DNA template). Research in the laboratory aims to uncover fundamental mechanisms used by the cellular transcription machinery and its regulatory factors to control mRNA synthesis. Transcriptional regulation is a key step in controlling processes such as cell growth, differentiation, development, and cellular stress response. Since misregulation of transcription is a major cause of human disease, deciphering transcriptional regulatory mechanisms can lead to understanding the molecular basis for defects leading to many diseases and syndromes.

Research Overview

Eukaryotic RNA polymerases are components of large protein machines that integrate numerous regulatory signals to precisely control gene expression. Key regulatory factors include gene-specific transcription factors that either activate or repress transcription in response to various signaling pathways. These factors often work via recruitment of transcription coactivators to gene regulatory regions. Coactivators are large protein complexes that interface with the basal transcription machinery and/or modify nucleosome positioning or covalent nucleosome modifications. Research in our laboratory aims to understand the function of the gene-specific transcription factors, how they interface with coactivator complexes and how these factors modulate early steps in the transcription pathway.

The lab uses a multi-disciplinary approach including molecular genetics, genomics, computational biology, biochemistry, structural, and biophysical methods to uncover new fundamental mechanisms used in gene regulation. We use S. cerevisiae (budding yeast) as our experimental system because of the powerful mix of genomics, molecular genetics and biochemical methods that can readily be used in this model organism. Because the transcription machinery and its regulatory factors are well-conserved throughout evolution, fundamental gene regulatory mechanisms in yeast are nearly always conserved in metazoans.