DNA

The diagram above illustrates regulatory networks within the gene structure, wherein certain parts of the genes are able to turn other genes on or off, akin to that of a small brain (like an earthworm brain).

Smart Junk
“Stam Lab” leads way in solving DNA puzzle

By any measure, Sept. 5 was a good day for John Stamatoyannopoulos, ’95, a UW genome scientist, a classics scholar, a tall man in a long white coat inscribed with the initials MD on the pocket below his lapel. On that day, “Dr. Stam,” as his students in the “Stam Lab” refer to him, was senior author of four articles published in the leading scientific journals of the day: Science, Cell and two in Nature. By day’s end, news from his UW laboratory and the labs of colleagues working on the federally funded Encyclopedia of DNA Elements (ENCODE) project had rocketed around the world.

For decades most scientists thought the bulk of the material in the human genome—up to 95 percent—was “junk DNA.”

It now turns out much of this “junk,” far from an evolutionary byproduct, actually contains the vital instructions that switch genes on and off in all kinds of different cells. Changes in these instructions can affect everything from color vision to whether a person develops diabetes or cardiovascular disease or a host of other conditions.

“The junk DNA concept, as it has come to color our perception of the human genome, is somewhat bizarre,” says Stamatoyannopoulos. “If you picked up a Chinese newspaper and you could read only one or two percent of the characters, would you automatically assume the rest was junk?”

The Human Genome Project sequenced the 3 billion letters or DNA bases that make up the genome, and it provided a basic catalog of genes, which occupy only about 2 percent of the genome. But understanding how genes turn on and off is vital to figuring out basic biological processes, like development, or how genes contribute to normal health and disease. It turns out—contrary to expectation—that there are a modest number of genes (around 20,000) but these genes are controlled by millions of DNA “switches,” with the whole unit functioning as a kind of operating system for the cell. The UW lab was the most prolific contributor to developing the first maps of these DNA switches, as well as a leading player in the “team science” approach of the 400- plus scientists working on ENCODE.

“We continuously generate data and almost immediately release it into public repositories so other scientists can look at it,” said Stamatoyannopoulos. The Internet and the ability to harness powerful advanced computers to manage huge amounts of data make a project like ENCODE possible. Scientists are now pursuing these genetic questions as if they were all working together to solve a very large puzzle.

As a physician-scientist, Stamatoyannopoulos is a guy with an unusual perspective on this work. For him, the prospect of using genetic information to improve patient care reminds him of the cancer patients he took care of as an oncologist in the Harvard hospitals in Boston. “Cancer medicine is unique. It’s very difficult but it’s also very rewarding. Patients develop a lasting relationship with their oncologist, and they really fight the disease together, through the ups and the downs,” he recalls.

In cancer, gene activity patterns go haywire. The information gathered during the ENCODE project will greatly help to decipher the gene-control pathways that are active in cancer cells but not normal cells. Stamatoyannopoulos and his colleagues have recently identified a few dozen kinds of genetic changes that affect gene switches and repeatedly turn up in the 17 most common kinds of cancer. This is one more step in learning what makes cancer cells behave the way they do—and potentially how to attack them.

Stamatoyannopoulos believes, as many now do, that we are nearing the day when doctors will be able to diagnose and treat cancer patients based largely on what the genome of their cancer has to say about their particular disease. As a researcher, he hopes to lay the basis for changing the way we will care for patients in the future.

Until now, Stamatoyannopoulos says, with no small amount of disenchantment, “standard chemotherapy, bone marrow transplant being the main exception, is the only drug regimen that has ever truly cured cancer—and we still don’t understand the reason chemo is so effective. The more we understand about what is genetically wrong with a given patient’s cancer, the more we will be able to understand why one drug combination is more effective than another.” He pauses to reflect for a moment.

“The trajectory I expect is that our whole approach to diagnosing and treating these diseases will be reshaped by our emerging knowledge of how the genome works.” —Julie Garner is a Columns staff writer

DID YOU KNOW?

Groundbreaking advances by UW Genome Sciences researchers:

  • Established pharmogenetics—the field based on the discovery that genes play a role in how a person reacts to drugs.
  • Collaborated in sequencing both the human and mouse genomes. Important because the lowly rodent shares almost all of its genes with humans.
  • Collaborated with other UW researchers to show that warfarin (Coumadin™) response can be affected by variations on the gene for vitamin K metabolism.
  • Sequenced the genome of a baby in the womb without invasively tapping its protective fluid sac.
  • Helped find a link between autism spectrum disorder and mutations that occur spontaneously near or during conception.
  • Discovered links between gene regulation and many major common diseases.
  • UW is one of eight sites in the U.S. working to revolutionize DNA sequencing by making the process faster and at a lower cost.

One Response to Smart Junk

  1. Carlos Gallego says:

    I’m glad to see a column in genomics. I’d love to see one in clinical genetics… specifically through the division of medical genetics. Just to let you know, we have the best adult geneticist division in the world, and we’re translating the information provided by genomicist into the clinic.

    Carlos Gallego
    Junior Faculty

What Do You Think?

Use the form below to comment on this story. Your email address will not be published. Required fields are marked *

*

Personal attacks, insults, profanity, solicitations and spam are prohibited. The UW Alumni Association reserves the right to remove comments. For more information, please read our comment FAQ.


Join the UWAA