Gene Regulation & Expression

FOUNDATIONAL DISCOVERIES

The Role of Genes in Health and Disease

Genes are involved in the development of many illnesses, including cancer, which can develop when a mutated gene is expressed, or switches on, or when a tumor-suppressing gene is turned off. The study of gene regulation — how genes come to be expressed and how gene expression can be controlled — is an important area of research at Fred Hutch and is foundational to the design of many potential targeted therapies.

Our research in this area includes uncovering fundamental mechanisms that regulate how genes are turned on and off in normal cells and how the misregulation of these mechanisms can lead to cancer, as well as investigating the correlation between drug sensitivities and gene expression patterns or mutations. It also includes searching for mutated genes that confer a unique vulnerability to cancer cells and studying gene expression patterns that are associated with mutation status across all tumor types. 

Understanding How Gene Regulation and Expression Work

A number of Fred Hutch scientists are deepening our understanding of the fundamental processes that control whether genes are turned on or off. The founder of our Basic Sciences Division, Dr. Hal Weintraub, performed seminal work that helped establish this field, known as epigenetics. A clearer picture of these processes in normal cells informs our understanding of what goes wrong in cancer.

A cell's functions are determined by which genes are turned on, how strongly and when. Major changes in gene expression underlie changes in cell state, including cell growth and a stress-resistant state called quiescence. Our scientists study how the organization of our chromatin - the DNA packaging molecules that help organize our DNA - regulate gene expression. They seek to understand how cells modulate gene expression by modulating chromatin and DNA organization. Fred Hutch researchers have done pioneering work in the areas of gene regulation, chromatin organization and cell cycle state, including quiescence.

Gene expression is important because a specific protein can be produced only when its gene is turned on. But it takes more than one step to get from gene to protein, and the process of building proteins is a key step in the gene expression pathway that can be altered in cancer. Our researchers study how changes in protein production can underlie cancer and may be potential therapeutic targets. 

Manipulating Gene Expression to Treat Disease

Several of our scientists study gene regulation in specific cancers, including cancers of the blood, lung, pancreas and prostate. They seek treatment strategies that halt or reverse tumor growth by targeting the altered gene expression patterns seen in these cancers. Our researchers are also exploring strategies to block deleterious gene expression in facioscapulohumeral muscular dystrophy.

Cell-based therapies — including stem cell and bone marrow transplants — are becoming a standard of care for many cancers and other diseases, including diabetes. Engineered immune cells, which have been programmed to fight cancer, are an exciting outgrowth of stem cell transplantation research. Scientific groups at Fred Hutch are working to develop better-engineered cell-based immunotherapies and create methods to make the approach less costly and more widely available.  

Left: Lung cancer. Right: Dr. Hatice Seda Kaya-Okur works the robotic pipette machine in the Henikoff Lab.

Photos by Fred Hutch Experimental Histopathology (left) and Robert Hood / Fred Hutch (right)

Using Genes to Develop Targeted Drug Therapies

Several labs at Fred Hutch are investigating the correlation between drug sensitivities and gene expression patterns or mutations. Specific patterns of gene expression may define tumor subtypes and support a more targeted approach to therapy. Our scientists are working to identify gene expression patterns that will improve patient survival by providing information about tumor prognosis and sensitivity to specific therapies. These insights will help oncologists better tailor treatment to individual patients.

Maria McSharry, right, teaches lab procedures to April Lo in the Berger Lab at Fred Hutch.
April Lo, left, and Maria McSharry in the Berger Lab. Photo by Robert Hood / Fred Hutch
Last Modified, November 07, 2019