Washington University’s renowned Genome Center has been renamed the Washington University Genome Institute. With the name change comes a new focus on multi-disciplinary, genome-based investigations to uncover the genetic underpinnings of human diseases.
The institute remains under the leadership of Richard K. Wilson, PhD, and Elaine R. Mardis, PhD, director and co-director, respectively, and associate directors Timothy Ley, MD, and George Weinstock, PhD. These scientists are now joined by a number of collaborators, including Washington University oncologists, pediatricians, neurologists, immunologists and infectious disease physicians, and by researchers with expertise in population and statistical genetics. Together, these specialists will work shoulder-to-shoulder with the institute’s genome scientists.
“Our scientists have long been at the forefront of genome sequencing,” says Larry J. Shapiro, MD, executive vice chancellor of medical affairs and dean of Washington University School of Medicine. “The institute’s focus on understanding human health and disease at the DNA level will revolutionize the way doctors diagnose and treat disease and move us closer to an era of personalized medicine.”
The Washington University Genome Institute is one of three federally funded large-scale genome centers in the nation, along with The Broad Institute in Cambridge, Mass., and The Human Genome Sequencing Center at the Baylor College of Medicine in Houston.
The institute’s scientists are pioneers in using a comprehensive, genome-wide approach to unravel the genetic basis of cancer. By sequencing the genome of a patient’s tumor and comparing it to the genome of a normal, healthy cell from the same person, the researchers can find critical mutations that likely contributed to the patient’s cancer.
To date, Wilson, Mardis and their colleagues have sequenced the genomes of nearly 300 cancer patients and their tumors. They will sequence hundreds more cancer patients’ genomes in the next several years to help build a base of knowledge to understand how specific mutations influence treatment outcomes. This work leverages the strengths of the Siteman Cancer Center, an NCI-designated comprehensive cancer center at Barnes-Jewish Hospital and Washington University School of Medicine.
“Cancer genomics will continue to play a prominent role at the Washington University Genome Institute,” Wilson says. “But we’ll also be sequencing the genomes of patients with heritable diseases and those with infectious diseases to identify novel features that underlie those conditions. Close collaborations with physicians who treat these patients will be key to our efforts.”
Work is already under way in patients with retinitis pigmentosa and macular degeneration, both of which cause blindness. The scientists also will sequence the genomes of patients with cleft lip and palate, type II diabetes, autism and metabolic syndrome.
On the infectious diseases front, the immediate focus is on sequencing the drug-resistant bacterium MRSA (for methicillin-resistant Staphylococcus aureus) and the genomes of patients with MRSA infection to determine whether mutations in genes that control the immune system leave some patients more vulnerable to severe infection and death.
The institute, with its dedicated technology and applications development group, has helped to drive recent advances in sequencing technology and associated data analysis that now make it possible to sequence a patient’s genome at a cost and speed that was unimaginable just a few years ago.
“We’re also getting a closer look at the complexity within the human genome,” Mardis explains. “We’re not just sequencing DNA but also RNA from the same patient samples and correlating these findings to clinical information. We can identify known and novel micro RNAs that regulate when genes are turned on and off, and we are detecting changes in the patterns of methyl groups on the genome that influence gene expression. These additional data types are critical for gaining a comprehensive understanding of diseases.”
Mardis predicts that in the not-too-distant future, sequencing technology will transition from its primary use as a research tool to a diagnostic tool that can help doctors predict the course of disease or the best treatment option. She and her group are actively working toward this goal, Mardis says.
Over time, a more complete understanding of the genome can help scientists design pharmaceuticals that more precisely target mutations that underlie cancer or other diseases.
The institute traces its history to the launch of the Human Genome Project in 1990. It was then that Washington University’s scientists received funding from the National Institutes of Health (NIH) as part of the international effort to sequence the first human genome. In all, they contributed 25 percent of the finished sequence.
The Washington University Genome Institute plays a leading role in many NIH-funded projects, including the Cancer Genome Atlas Project, to sequence the DNA of cancer patients; the Human Microbiome Project, to sequence the genomes of hundreds of microbes involved in human health and disease; and the 1,000 Genomes Project, to catalog the immense human variation written into the genetic code. Additional NIH funding has provided for sequencing the DNA of various model organisms, including the nematode worm, Caenorhabditis elegans, and the mouse. Projects to sequence the genomes of the chimpanzee, macaque monkey and the orangutan are aiding the study of human and mammalian evolution.
The institute also is collaborating with St. Jude Children’s Research Hospital to decode the genomes of more than 600 pediatric cancer patients as part of an unprecedented effort to identify the genetic changes that give rise to some of the deadliest childhood cancers.
Since its inception, the Washington University Genome Institute has received more than $750 million in research funding. In recent years, the institute received $25 million in federal stimulus funding, with about half dedicated to expand its high-powered data center. The facility’s sophisticated computer networks store massive amounts of genomic data used to identify the genetic origins of cancer and other diseases.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth 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.