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School of Medicine expands mission of McDonnell Genome Institute

Will apply its powerhouse DNA sequencing to precision medicine

by Julia Evangelou StraitFebruary 14, 2019

Matt Miller

The McDonnell Genome Institute at Washington University School of Medicine in St. Louis is entering a new era of genomic medicine, expanding its capacities beyond genome sequencing and adding a new and vital focus on understanding how genetics influences health and disease.

Jeffrey Milbrandt, MD, PhD, recently appointed executive director of the McDonnell Genome Institute, says the Genome Institute will continue its leading work in genome sequencing, and it will add new capacities to connect the wealth of data it generates to the specifics of patient care.

The McDonnell Genome Institute is one of a handful of large sequencing centers in the United States that has played a leading role in the genomic revolution in medical science. In the 1990s, at the dawn of the genomic era, the Genome Institute played a key role in the Human Genome Project, funded by the National Institutes of Health (NIH), contributing 25 percent of the sequence data.

Washington University researchers at the McDonnell Genome Institute were also the first to conduct large-scale genome sequencing studies of cancers, in an effort to identify the mutations that underlie tumors. This work has led to changes and improvements in the way many cancers are treated.

According to Milbrandt, the time is ripe for genome science to expand from sequencing genomes to a new focus on understanding the functional aspects of the genetic code. Scientists and doctors want to be able to specify which DNA variations are most meaningful to health and disease and then find ways to act on that knowledge to improve patient well-being.

“As more and more genomes have been sequenced, we have learned that all of us have thousands of genetic variants, but most of them are inconsequential or of unknown significance. Identifying which ones of those are important for disease is the essential question,” said Milbrandt, also the James S. McDonnell Professor and head of the Department of Genetics. “The role that I think the Genome Institute will play over the next decade will be to devise rapid and efficient ways to separate the genomic wheat from the chaff, so to speak. We want to identify those DNA variations that are crucial to the disease process, so we can develop better treatments.

“With that in mind, I see the McDonnell Genome Institute serving as a hub for precision medicine at Washington University,” Milbrandt added. “This will be a major transformation, from the current concentration on ‘reading’ the genome to one focused on interpreting genome variation associated with disease, followed closely by the era of ‘writing’ the genome, where we alter the genome to prevent or treat disease. We will continue large-scale sequencing activities, but we also want to understand how changes in the genome contribute to disease so that we can use that knowledge to development new treatments.”

Milbrandt envisions the Genome Institute adding cutting-edge functional studies, melding high-throughput imaging capabilities with the ability to analyze the genomics of a single cell, to identify DNA variants that cause disease and can be targeted for therapy.

“Jeff Milbrandt’s vision for the future of the McDonnell Genome Institute at Washington University will bring its massive DNA sequencing resources to bear on the challenge of integrating precision medicine into standard medical practice for all patients,” said David H. Perlmutter, MD, executive vice chancellor for medical affairs and the George and Carol Bauer Dean of the School of Medicine. “He will build on the legacy and strengths of the Genome Institute by expanding its research from gathering and analyzing genomic data into understanding how differences or changes in the genome impact health and disease, boosting our ability to find the right treatment for the right patient at the right time.”

Current centers providing genome sequencing and genome engineering established by the Department of Genetics will be brought under the McDonnell Genome Institute umbrella, including the Genome Engineering and iPSC Center (GEiC) and the Genome Technology Access Center (GTAC).

“We want the Genome Institute to be an important resource for all investigators at Washington University and throughout the Midwest,” Milbrandt said. “We have scientists who have spent their lives dissecting the causes of disease in the laboratory. We have physicians who treat patients with these diseases in the clinic. And we have computer scientists and informatics specialists analyzing enormous genomic and clinical datasets. Now, we want to cultivate an environment where we can merge that expertise together to enhance our ability to make new discoveries and develop new treatments.”

With Milbrandt at the helm, the Genome Institute also will have a steering committee helping guide it through this transition period. Members of the steering committee are Perlmutter, Victoria J. Fraser, MD, the Adolphus Busch Professor and head of the Department of Medicine; Gary A. Silverman, MD, PhD, the Harriet B. Spoehrer Professor and head of the Department of Pediatrics; and Philip Payne, PhD, the Robert J. Terry Professor and director of the Institute for Informatics.

“Together with its talented and dedicated staff and affiliated centers, the Genome Institute is poised to make important contributions to the personalized medicine initiative at Washington University School of Medicine,” Milbrandt said.

Washington University School of Medicine’s 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.