Wrestling with the Mysteries of Diabeties

There isn't much about diabetes Dr. William L. Lowe Jr. hasn't been involved with, but perhaps the best lesson he's learned is that team science is not just some cliche. For a researcher, it can be a survival strategy.

"Collaborations are critical," Lowe says. "I am happiest and most proud when I'm able to work in teams of investigators with such diverse skill sets that the whole is greater than the sum of its parts."

Lowe, an AAAS Fellow, has spent his career wrestling with the mysteries of diabetes. A longtime researcher and the vice dean for academic affairs at the Northwestern University Feinberg School of Medicine in Chicago, Lowe has come at diabetes through insulin-like growth factors, genetics, metabolomics, pancreatic islet transplantation, and repeated dives into gestational diabetes and its long-term effects on both mothers and their babies.

He's done candidate-gene studies, genome-wide association (GWAS) studies and basic science; he's dabbled in bioengineering; and now he's working in silico to analyze masses of data he and other researchers have compiled.

Genetics research has moved quickly; in the trenches in the early days of his career, Lowe got used to the lightning speed with which the consensus could turn to a whole new way of doing things, with federal grant money following close behind. A successful researcher needed to stay on his toes.

Linking up with another researcher who had a grant, access to a cohort, skill with a new technology, or even just an interesting idea that might mesh with one of his own has been Lowe's fallback tactic for keeping his work alive, fresh, and relevant to the leading edge of our understanding of diabetes. This has meant constantly learning, adapting, meeting new people, writing another grant or two, keeping his antennae up for possibilities.

"His ability to thrive in multiple areas of science is a sign of how he is as a scientist; it speaks to his overall intellectual ability," says Feinberg colleague Brian Layden MD, who has collaborated with Lowe on gestational diabetes. "He was involved in a field where things have evolved rapidly. Typically, as different areas fizzle out, those scientists disappear, but that hasn’t happened in his case."

Lowe's work with diabetes began in 1984, with a fellowship at the National Institutes of Health, looking at the function, influence and genetics of peptides that included an insulin-like growth factor called IGF1.

Those were “the candidate-gene days,” Lowe says, the era when researchers drilled down into one gene that seemed a likely candidate to cause a particular phenotype. That technique has been supplanted by the GWAS approach.

"What we didn't realize at the time was that you needed large cohorts to validate what you were seeing,” he says. By 1993, Lowe, now at Feinberg found that investigating “gene expression alone was not enough for funding."

However, Richard Cooper MD, at nearby Loyola University Stritch School of Medicine, was exploring the role of genes in hypertension and obesity with a cohort of Nigerians and African-Americans from a Chicago suburb.

"They were looking for a place to do genotyping. We had the infrastructure; they had the cohort. We hooked up, if you will," Lowe says. "Like most candidate-gene studies, it yielded only a limited amount of new data."

However, that work did position Lowe to jump into the NIH-funded Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study of glucose levels in 23,000 pregnant women all over the world, with a Feinberg colleague, Boyd Metzger MD. Lowe is still involved with HAPO, which now is looking at the possible ongoing effects of glucose levels during pregnancy on about 25 percent of the original HAPO mothers and their preteen children.

"It has the potential to have a real impact on health outcomes," he says, as glucose levels during pregnancy do appear to have an effect on the metabolic health of children well past infancy.

Tim Reddy, Assistant Professor of Genome Sciences at Duke University Medical School in Durham, NC, who met Lowe at an NIH "speed dating" event for researchers looking for collaborators a few years ago, has worked with him on exploring the effects of gestational diabetes on babies. Reddy says of Lowe, "He's found a way to have something going in every single promising technology possible, in order to go forward on maternal health. He has a depth of understanding that is really well complemented by a willingness to take new and risky research endeavors."

As for those early days in genetics, Lowe says, "When you were in it, I'm not sure you felt like it was a revolution, but looking back at the rapidity with which we were able to move forward, especially once the genome was sequenced, it was pretty remarkable." Now, he says, the challenge lies in analyzing the data that came out of that effort.

When he was in high school in North Carolina, Lowe recalls, all his friends wanted to be either doctors or lawyers. "I was better at science, so I was on the doctor side of things," he recalls.

In college at the University of North Carolina at Chapel Hill, he got involved with "a couple of research projects" that sealed the deal, including a summer project with slime mold, through the National Science Foundation.

"It was so much fun, reading the literature, coming up questions, talking with professors about using different technologies," he recalls. "It was obvious to me that research was what I really liked."

What he likes best, Lowe says, "is the creative process of thinking about the questions that need to answered and then finding ways to answer them. Crazy as it is to say, writing grants is actually fun for me."