The Hahn Laboratory

Welcome to the Hahn Lab 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). 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. Deciphering these regulatory mechanisms can lead to understanding the molecular basis for defects leading to many types of human disease.    

Research Overview

Eukaryotic RNA polymerases are components of large protein machines that integrate numerous regulatory signals to precisely control gene expression. Most subunits of the transcription machinery are essential for viability and regulation of transcription is a key step controlling many cellular processes. Since the core transcription machinery is the ultimate target of many signaling pathways, identifying regulated and rate limiting steps in transcription initiation leads to understanding how many biological signals converge to control specific programs of gene regulation. Misregulation of transcription is a major cause of human disease and our work addresses the molecular basis for many of these defects. Major research areas in our laboratory are the mechanisms of transcription activation, the genome-wide role of coactivator complexes and mechanisms of transcription initiation.

The lab uses a multi-disciplinary approach including molecular genetics, genomics, computational biology, biochemistry, structural, and biophysical methods to uncover new mechanisms used in gene regulation. Much of our work uses new technologies and approaches to understand the action of large protein complexes, which are often regulated by surprisingly flexible and dynamic protein-protein interactions. These new approaches are also adaptable for understanding the architecture, conformational changes and mechanisms of large protein and protein-DNA complexes involved in other cellular processes.

We use S. cerevisiae (budding yeast) as our experimental system because of the powerful mix of available biochemistry, proteomics and genetic approaches that can be applied 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 used in metazoans. These mechanisms form the molecular basis for understanding regulated and rate-limiting steps that are at the endpoint of many signaling pathways controlling growth, homeostasis and the response to stress.