Dr. Steven Hahn elected to American Academy of Microbiology

Revealed fundamental properties of molecular machinery that creates mRNA
Dr. Steven Hahn
Dr. Steven Hahn studies the molecular mechanisms that govern gene transcription. Robert Hood / Fred Hutch News Service

Fred Hutchinson Cancer Research Center investigator Dr. Steven Hahn has been elected a fellow of the American Academy of Microbiology, an honorific leadership group within the American Society for Microbiology. Hahn was one of 65 fellows elected in 2022 following a highly selective, peer-review process that is based on nominees’ records of scientific achievement and original, microbiology-advancing contributions.

Hahn, a professor of the Basic Sciences Division, studies the components of the molecular machines that make messenger RNA, or mRNA, the molecules that transmit the information in our genes to the protein-building factories in our cells, and how they work together. When the workings of this machinery, made up of more than 100 separate proteins, go wrong, these changes can drive disease, including cancer. Hahn’s insights help researchers understand when the machinery’s function has changed, and how that change could shape disease.

“Steve is an exceptionally creative scientist,” said nominator Dr. Stephen Buratowski, a biological chemist now at Harvard University who collaborated with Hahn on several early discoveries. “Many of his multiple outstanding discoveries are now ‘textbook’ facts taught to all undergraduates in basic molecular biology classes.”

Early in Hahn’s scientific career, few of the components of the machinery that reads, or transcribes, genes were known. With Buratowski, Hahn identified several of the genes involved and purified their proteins, helping scientists understand more about the transcription machinery and how it works — a mystery that researchers, including Hahn, are still untangling. With structural biologist Dr. Paul Sigler at Yale University, Hahn revealed how several key proteins in this complex interact with each other.

“This honor recognizes Steve’s outstanding contributions to understanding the process of transcription initiation. He is fearless about approaches and has always tackled the question using the best approach regardless of how difficult it is,” said Hutch Senior Vice President and Basic Sciences Division Director Dr. Sue Biggins. “His work has led to a detailed mechanistic understanding of the mediator complex and its functions, and this is wonderful recognition of his numerous contributions throughout the years.”

Hahn’s early work focused on the universal machinery that cells use to transcribe every gene. More recently, he and his team have focused on regulation of specific genes, which can vary by cell type and developmental stage. In collaboration with biochemist Dr. Rachel Klevit at the University of Washington, Hahn has worked to understand how the proteins that bind DNA, called transcription factors, interact with intermediate proteins, called transcriptional activators, which link transcription factors with the universal transcription machinery.

Often, interacting proteins use defined structures that allow them to fit together like a lock and key. But transcription factors and activators can’t work together this way — there are too many different types with too many different structures. A tight fit with one activator would leave a transcription factor unable to bind to another. Hahn and Klevit found that transcription factors get around this problem by using regions with less defined structure to interact with activators. This allows the universal machine to bring some control to gene transcription while interacting with an array of structurally dissimilar activator proteins.

“It’s a nice honor to be recognized by my peers. But it’s not just me — I’ve had such fantastic people in my lab, from research technicians to postdocs to graduate students, as well as collaborators. It’s really a tribute to their work,” said Hahn, who also attributed his successes to the Hutch: “It’s such a collaborative environment to do research.”

Sabrina Richards, a staff writer at Fred Hutchinson Cancer Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a PhD in immunology from the University of Washington, an MA in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at srichar2@fredhutch.org.

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