Like any researcher who studies Drosophila melanogaster, Seung Kim has inadvertently inhaled, eaten, and guzzled dozens of stray fruit flies. "I drank them in my coffee for years. Maybe I have their DNA inside me," he says with a laugh. But that doesn't deter him from using fruit flies to unmask the secrets of organ development.
Kim, who is at Stanford University, is leveraging the fruit fly and other organisms to uncover the molecular and cellular instructions for making pancreatic islet cells, which secrete insulin and, when broken, cause serious diseases such as diabetes.
As an HHMI investigator, Kim will interlace his work with flies, mice, and human pancreatic cells, making his lab a triple threat in their work to understand how islet cells develop, function, regenerate, and change in disease. "We're broadly interested in deciphering the rules for making an organ, and flies are a marvelous tool for gene discovery," says Kim, explaining that his research touches on areas from stem cells to cancer treatment. "We can use fly genetics to identify regulators of these cells and regulators of their functions."
Kim's group has shown that fruit flies have endocrine cells that work the same way as human islet cells—they respond to glucose, measure its levels, and produce molecules like glucagon and insulin, hormones that regulate metabolism. Before Kim's discoveries, scientists did not know if fruit flies had the equivalent of a pancreas—but his findings provide evidence that evolution has used, preserved, and refined the molecular regulators that control metabolism and growth from insects to humans.
Kim has also studied mouse and human cells as they march through development to become islet cells. "We're primed to exploit our discoveries in organisms like flies, but it's important to understand how mammalian pancreatic cells grow and develop. Human cells are not mouse cells or fly cells," Kim says. "We have lots to learn from the master, the human pancreas itself."
Specifically, he wants to understand the formation and growth of progenitor cells, "the cells that are primed to become islet cells." These cells were notoriously difficult to isolate and purify until Kim and his colleagues identified a set of protein markers that allows them to pick the cells out of groups using automated cell sorters. Having these cells in hand is a starting point to growing insulin-producing cells in the lab. Such knowledge is critical for advancing the nascent disciplines of stem cell and regenerative biology, which harbor the potential to create replacement cells for diseased tissue or to help the body regenerate its own healthy cells.
Insights about pancreatic development and growth may also help expose new treatments for cancers of the pancreas and other endocrine tissues, says Kim, whose training as a developmental biologist, internist, and oncologist, colleagues say, is unusually broad. Knowledge gained from studies of regenerating cells could be exploited to treat cancers. "On the one hand we're trying to figure out how to grow cells, and on the other hand we're trying to figure out how to kill them."
Kim was exposed to medicine from an early age—his father was a physician and his mother a pharmacist. He was also stimulated by the romance of science, a lesson imparted at age 14 when he read the Sinclair Lewis novel Arrowsmith and the Microbe Hunters by Paul de Kruif. "I thought there was something about Martin Arrowsmith and the scientists described in de Kruif's book that I wanted to emulate," Kim says. "Later in college, I read Molecular Genetics like an adventure story, whose heroes were all scientists."
Initially, his parents viewed a career in science as risky: "My family was somewhat against my being a scientist, a profession with too much of the 'unknown.' I think I can say they're convinced it was a great choice for me."
Kim considers himself lucky to have developed as a scientist in a golden age of biology. "I was fortunate to have opportunities as a young student, especially during my graduate school training, when I lived in a kind of dream come true. We had a very collegial atmosphere with driven people who trained me to think. I had great fun."
Kim sees his work as drawing together diverse lines of research to comprehend pancreatic islet development and growth. "In one mode, I'm an optimistic synthesizer, trying to focus understanding from multiple areas to solve one problem at a time. My other mode is anticipatory grieving, imagining contingencies and disasters. It's good to be both optimistic and realistic."