Unveiling insulin insights

The research of Michael M. Mueckler addresses epidemic problems such as obesity and type II diabetes

Good science requires knowing when to drop bad ideas, explains Michael M. Mueckler, Ph.D., professor of cell biology and physiology.

“You may have worked on something for two or three years,” he says. “But at some point, you have to look at the long series of results, use the data to evaluate your original hypothesis and, if necessary, reformulate your ideas and start over.

“Rigorous honesty is key to successful science,” Mueckler continues. “It’s very easy to get attached to pet hypotheses and then ignore data that contradicts them.”

Graduate student Matthew Storck (left) and Michael M. Mueckler, Ph.D., professor of cell biology and physiology, review a Glut11 expression profile. Mueckler says one of the things he enjoys most about the School of Medicine is working with students and young faculty. “Unlike other top medical schools, Washington University nurtures and supports young faculty,” he says. “It’s not the sink-or-swim policy that exists at some universities.”

Mueckler has faced the dilemma of a good-idea-gone-bad many times in his 21 years as a molecular biologist, and he’s learned from it each time.

The experience has helped him achieve an international reputation for innovative work in the areas of sugar metabolism and diabetes.

As a postdoctoral fellow at Massachusetts Institute of Technology in 1985, Mueckler discovered the first gene and protein that transport glucose into cells. The following year, he was recruited to Washington University, and three years later his laboratory cloned the gene for the glucose transporter 4 protein (Glut4).

The discovery brought new insights into the problems of obesity, insulin resistance and type II diabetes, all of which have reached epidemic levels among Americans.

Another turning point came in 2000 when then-graduate students Haru Murata, M.D., Ph.D., and Paul Hruz, M.D., Ph.D., now an assistant professor of pediatrics, discovered in Mueckler’s lab that drugs known as protease inhibitors — which are essential for prolonging the lives of people with HIV — block the action of Glut4. The finding may explain why many people using these drugs experience a loss of fat from the face and extremities, increased risk of heart disease and high rates of type II diabetes.

Most recently, Mueckler, along with Murata and Richard Hresko, Ph.D., research assistant professor of cell biology and physiology, led research that produced the first test-tube system for studying the sequence of events by which insulin triggers changes in cells, a process known as hormone signaling.

“Mike is able to look at the research that everybody is doing, understand its importance and develop clever new ways to approach the question, and he does all this with enormous energy and enthusiasm,” says Alan Permutt, M.D., professor of medicine and of cell biology and physiology and director of the Diabetes Research and Training Center. “He’s a marvelous scientist and a great colleague.”

Destined to be a scientist

Mueckler’s interest in science began at age 9 when his parents gave him a microscope for Christmas.

“I was fascinated by the ability to see things that were invisible to the naked eye,” he says. “From that time on, I wanted to be a scientist.”

A few years later, Mueckler used earnings from a paper route to set up a microbiology laboratory in his basement, complete with a stove-top autoclave, shelves of chemicals and cultures of bacteria from different environments. He read all he could find on microbiology and science pioneers such as Antonie van Leeuwenhoek, Louis Pasteur, Robert Koch and Paul Ehrlich.

His father, a machinist, died of renal cancer when Mueckler was 13. His mother, a housewife, then returned to work as an executive secretary.

“She was wonderfully tolerant and understanding about the chemicals and laboratory paraphernalia I had all over the basement,” he says.

His father never graduated from high school. He dropped out to play semi-pro baseball and was later drafted as a pitcher by the Philadelphia Phillies. Before he could report to spring training, he was drafted to serve in World War II.

“When my father became ill, he made my mother promise that my brother and I received a college education — no matter what,” Mueckler says. “She worked very hard to keep her word.”

Mueckler entered the University of Wisconsin with several scholarships. He earned a bachelor of arts in microbiology, graduating in 1976 with highest honors.

He remained there for graduate school as a National Institutes of Health predoctoral trainee, earning a doctorate in experimental oncology (the equivalent then to majoring in molecular biology) in 1982.

After his recruitment to Washington University as an assistant professor, he quickly rose through the ranks, becoming a full professor in 1995.

These days, he mostly enjoys analyzing data and designing experiments. He serves as associate director of the Diabetes Research and Training Center and as editor in chief of the American Journal of Physiology: Endocrinology and Metabolism. He also enjoys working with students, and he received a Distinguished Service Teaching Award from the University in 2000.

“Mike is highly organized, very smart and pays close attention to detail,” says Philip D. Stahl, Ph.D., the Edward Mallinckrodt Jr. Professor of Cell Biology and Physiology and head of the department. “He’s also intense and engaging, and he does a good job teaching medical and graduate students. He’s fair but has high standards.

“He’s also a great colleague and individual, and we’re delighted to have him.”

At home, Mueckler relaxes by watching movies and reading biographies, especially ones about scientists.

Michael M. Mueckler, Ph.D.

Title: Professor of cell biology and physiology

Years at the University: 17

Birthplace: Racine, Wis.

Education: B.A. in microbiology, University of Wisconsin, 1976; Ph.D. in oncology, University of Wisconsin, 1982

University positions: Associate director of the Diabetes Research and Training Center

Honors: Boehringer Mannheim/JDFI Diabetes Research Award, 1997; the American Diabetes Association Outstanding Scientific Achievement Award, 1998; the University’s Distinguished Service Teaching Award, 2000

Currently, though, he is reading a biography about Bob Dylan, which isn’t surprising because he enjoys listening to music from classical to rock and also plays guitar. He also collects the instrument and owns 10 — seven acoustic and three electric. His personal favorite is an acoustic jaguar-claw mahogany with a cedar top and custom pearl inlay, custom made by Lance McCollum, a well-known California guitar maker.

He and his former wife and now-significant other, Susan Mueckler, enjoy biking and jogging, dancing, travel, gourmet food — and a good vodka martini. They have a daughter, Alexandra, 19, who studies computer science, and a son, Sam, 17, who plays guitar, writes songs and wants to be a musician.

Unbreakable bonds

Mueckler came to the University because of the research under way in diabetes, endocrinology and cell biology. And he’s been pleased with the decision ever since.

“Unlike other top medical schools, Washington University nurtures and supports young faculty,” Mueckler says. “It’s not the sink-or-swim policy that exists at some universities. At Washington University, department chairs and division heads, for the most part, work hard to help young investigators in their research.”

Mueckler credits many senior faculty for helping his career along the way, including Stahl and Permutt. Mueckler says shortly after he arrived on campus, Permutt, then a full professor, spent a year’s sabbatical in Mueckler’s lab to learn molecular biology, then a relatively new field. At the same time, Permutt taught Mueckler a tremendous amount about diabetes.

“We developed a wonderful synergistic relationship that still exists,” Mueckler says. “You don’t see interactions like these in many other medical schools, especially between the basic and clinical sciences. Many of my closest collaborators have been clinicians here at the School of Medicine. We sought each other out and formed career-long relationships that hopefully have been helpful for us all.”