Awardee Profile - Louis Muglia

Louis Muglia, M.D., Ph.D.

2007 - Dr. Louis Muglia likes to spend Saturday mornings in his office.

"It's the time where I have the most freedom to think and plan for an extended period," he said when reached in his office on a recent Saturday morning. "I can really focus without trying to balance calls from patients and administrative obligations."

On weekdays, however, Dr. Muglia, a physician-scientist and professor of pediatrics at Washington University School of Medicine in St. Louis, gets interrupted a lot. That's perhaps because he has four jobs in one: Scientist, physician, teacher, and administrator.

But even the precious silence on Saturday was interrupted a few weeks ago when one of Dr. Muglia's studies made headlines, including one in the The New York Times. In the few days after the study appeared, he gave about 30 interviews.

The study used public records of all births in Missouri between 1989 and 1997. It found that blacks are about four times more likely than whites to have recurrent preterm births. And that's even after accounting for possible social and environmental factors like amount of prenatal care, smoking, or educational status. That suggests, although it doesn't prove, that a genetic difference could explain at least part of the higher risk for black people to have preterm births.

"I was actually quite surprised by the amount of attention," Muglia says.

But he can see where the interest might come from, he adds. "It's known that preterm birth is an important issue, and that here is a major racial disparity," he says. "I think people are hungry for an answer."

His hometown paper, the St. Louis Post-Dispatch, ran a front page article on his study. As a result of his recent fame, Dr. Muglia has even started to Google himself. "You wonder where this stuff is coming out," he says. Still, he seems uncomfortable with being in the spotlight, and says he is happy the Post-Dispatch didn't run his picture with the article.

"He is very understated about everything," says Dr. Jonathan Gitlin, a pediatrician and geneticist who works in the same building upstairs.

Dr. Muglia is humble, too. Asked about teaching awards he has received at Washington University, he says that he got the awards probably "not because I am particularly good, but because I really enjoy doing what I do, and that enthusiasm comes across."

Indeed, Dr. Gitlin says, when Dr. Muglia has a new finding, he "bubbles over with enthusiasm to show it and we talk about it." Often, that happens on Saturday mornings. "Sometimes, we are the only two people in the pediatrics research building," Dr. Gitlin says.

Dr. Gitlin recalls one such morning several years ago when Dr. Muglia came into his office to show him a gel. That gel showed that Dr. Muglia had successfully engineered mice that lack the receptor for glucocorticoid type hormones in T-cells of the immune system. "You realize that there is going to be a decade of questions that you can ask around it," Dr. Muglia says of such a moment. The mice, he found later, died because they couldn't suppress inflammatory responses.

Dr. Muglia isn't just passionate about his research. He also loves playing the guitar. In fact, in high school in Detroit, he played jazz in the high school band, he played at weddings, and he taught at local music studios. In college at the University of Michigan, he played in a punk band, and as a postdoc in Boston, he took classical music lessons. He still plays on the weekends, but his main love remains science. "I was nowhere near good enough to make it as a professional guitarist," he says. "So I bagged that interest and now do it for fun."

As a researcher, he has come a long way. In high school, he enjoyed mathematics and science, and in college, he joined a lab to study the structure of the way cells package their DNA. As an M.D.-Ph.D. student at the University of Chicago, he studied how genes are turned on and off during development.

He is still interested in the way genes work, but now uses genetically engineered mice to understand their function. The first mice he made, during his postdoc at Children's Hospital in Boston, lacked the gene for corticotropin releasing hormone, or CRH. He found that the animals died because their lungs didn't develop properly. It was the first time that CRH - otherwise known to induce stress response - was found to also be required for development.

That study, published in the journal Nature in 1995, helped him land a position as an assistant professor at Washington University School of Medicine in 1996, he says. It also helped him get a Burroughs Wellcome Fund Career Development Award that enabled him to get started in his own lab. The award, he says, "allowed me to perform genetic modeling in mice, which is a very important but also very costly way of doing biology."

Once in his own lab, Dr. Muglia started to study the hormones that control when babies are born. He was interested in the biology of preterm birth ever since his time as a resident and clinical fellow in pediatrics at Harvard Medical School from 1988 to 1990. "We saw an enormous number of extremely preterm babies that would have compromised health for the rest of their lives," he says.

But finding the factors that control the timing of birth turned out to be more complicated than he thought. For example, the hormone oxytocin seemed like a good candidate because it is routinely given to mothers to get labor started. But when Dr. Muglia's lab made mice that lack oxytocin, they gave birth just fine. (He later found that oxytocin is involved in the timing of birth, but in a rather convoluted way).

So Dr. Muglia started to focus on another hormone, progesterone, which is produced by the ovaries in mice and the placenta in humans. At least in mice, a fall in progesterone levels about 12 hours before birth induces uterus contractions and therefore labor. Indeed, Dr. Muglia's group found mutations in genes that change progesterone levels and therefore either delay or accelerate the timing of birth.

Still, the situation is different in humans, where progesterone levels don't fall before birth. "We don't know how to relate the findings in mice to human pregnancy," Dr. Muglia says. "We don't know which signaling molecules are important."

To find out, Dr. Muglia is collaborating with Washington University geneticist Dr. Justin Fay, an expert in comparing the sequences of entire genomes. Dr. Fay was interested in part because his son had been born six and a half weeks early.

The two came up with a way to find candidate genes that might regulate the timing of birth in humans. They reasoned that in evolution, human gestation has been pushed to relatively earlier times to avoid any problem with birth because human head size keeps growing. But this trend only seems to be happening in humans, not in other primates. This means that genes that control gestation length should be changing more rapidly in humans.

That's why Dr. Muglia and Dr. Fay are looking for sequences that mutate more rapidly in humans than in other primates or mammals. Such sequences, they figure, may harbor genes that shorten human pregnancy. Once they have found candidates, they plan to check if they can find them more easily in people with premature babies.

One day Dr., Muglia hopes, this research will enable doctors to give women  dietary supplements or medications that can prevent premature birth. "If we can really identify a gene that's central to either normal or preterm human birth," Dr. Muglia says, "I think that'd be one of those moments where you say, 'this is just unbelievable.'"

As soon as he makes that discovery, he'll likely run upstairs to Dr. Gitlin's office to tell him about it.

Chances are, it will be on a Saturday morning..

Andreas von Bubnoff is a freelance writer based out of Washington D.C.