HAHN LAB

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). Work in our laboratory aims to discover fundamental mechanisms used by the cellular transcription machinery and its regulatory factors to control RNA synthesis. Transcriptional regulation is a key step for controlling cell growth, differentiation, development, and cellular stress response. Deciphering these regulatory mechanisms leads to understanding the molecular basis for defects leading to many types of human disease.


Research Overview

Our research aims to decipher fundamental and conserved mechanisms used by the RNA polymerase II transcription machinery and its regulatory factors. In eukaryotes, RNA polymerases are components of large protein machines that integrate various 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 cell identity, cell growth, development and stress response. Since the core transcription machinery is the 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.

The two major research areas in our laboratory are:

1. The mechanism of transcription initiation

2. Mechanisms used by factors that activate transcription

We use a multi disciplinary approach including biochemical, molecular, genetic, 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 genetics approaches that can be applied in this model organism. Since the transcription machinery and its regulatory factors are well conserved throughout evolution, gene regulatory mechanisms in yeast are nearly always used in mammalian cells. 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.

Structure of the TATA binding protein
Structure of the TATA binding protein (TBP; red) in complex with DNA. This protein-DNA complex nucleates assembly of the polymerase II transcription machinery at a promoter. (see Kim et al, 1993; Geiger et al, 1996)