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Regenerative medicine

An internationally recognized developmental biologist and leader in cellular regeneration, Jonathan Slack, Ph.D., plans to build upon the Stem Cell Institute's already firm foundation.

New director Jonathan Slack, Ph.D., has big ideas for growing the Stem Cell Institute

Jonathan Slack, Ph.D., is one of those self-described science addicts. A native Brit, he finished his first degree in biochemistry at Oxford and quickly became inspired by one of the world’s oldest questions: How do embryos develop from eggs? His scientific curiosity led him to the rarefied field of developmental biology. And in 1986 he became the first to identify an inducing factor called the fibroblast growth factor in the frog embryo—a major discovery that was later shown to contribute to the formation of the head-to-tail pattern in all vertebrate embryos.

It was a breakthrough moment in the study of embryology, and Slack still looks back on it with awe. As the new director of the University of Minnesota’s Stem Cell Institute, he’s carried that sense of discovery across the Atlantic with him.

“Stem cell research is essentially applied developmental biology,” explains Slack. “After 32 years studying embryos in a lab, I want to see if some of our theories can be put into practice.”

Fertile ground

As Slack knows, the University’s Stem Cell Institute is an incubator for new ideas. Established in 1999 during the early days of stem cell research, it is where Catherine Verfaillie, M.D., and her team made breakthrough discoveries demonstrating the potential of adult stem cells to treat disease. It is also the first place dedicated to studying the potential of stem cells using an interdisciplinary approach. While this was a new idea at the time, it has become a model for scientific inquiry at the University of Minnesota.

“Some of the greatest discoveries happen where disciplines touch,” explains Deborah Powell, M.D., dean of the Medical School. “We have seen that when scientists and clinicians work together, advances can happen more quickly. Our many interdisciplinary institutes and centers offer opportunities for faculty to brainstorm and make discoveries that lead in exciting new directions.”

Today the Stem Cell Institute draws on the specialized knowledge of researchers from across the University. The bulk of their early work has focused on basic science, but as more is known about how stem cells proliferate and differentiate, the possibilities for translational and clinical research are profound and growing. Stem Cell Institute researchers are committed to finding ways to translate their fundamental understanding of stem cells into new therapies, and then applying those therapies through animal—and eventually, human—clinical trials.

Slack is convinced that this path of research will benefit future generations. “Lives are already being saved,” he says, pointing to cell transplantation therapies that are currently used to treat a variety of conditions, including leukemia, diabetes, and burns. Bone marrow and umbilical cord blood transplants are the best-known examples. Another long-standing application uses skin cells grown in culture to create a new epidermal layer for burn victims. More recently, grafts of limbus cells, found where the cornea and white of the eye meet, have been used to repair chemical burns to the eye. And transplants of insulin-producing pancreatic islet cells into the liver—a technique pioneered at the University—are effective at treating those with the most severe form of diabetes.

According to Slack, these examples are only the beginning of what will be possible once scientists learn how to control the growth, behavior, and differentiation of stem cells. And as our population ages, the need for cell-based therapies should only increase.

“Just about everything we die of in old age is due to tissue-level failure,” says Slack, referring to diseases that break down the body’s organ, muscle, connective, and nervous tissues. “All of these are potential areas for stem cell research.”

The tadpole’s tail

Slack has used a green fluorescent protein to mark specific genes in transgenic tadpoles and this transgenic

This whole area of science was virtually unknown during Slack’s early education. After earning his bachelor’s degree, he decided he wanted to pursue a Ph.D. in something involving nucleic acids because “it was clear even then that they were the molecules of the future.” His first lab experiences were under what he calls Britain’s old “sink-or-swim” philosophy, which allowed students to succeed or fail on their own—a way to quickly identify the few capable of making a contribution to science. Slack swam with the best in his class but emerged uninspired from his Ph.D. in precloning molecular biology.

Then he discovered Principles of Embryology, a 1956 textbook written by the British scientist and philosopher Conrad Waddington. Slack heard Waddington speak at a seminar in 1973 and was fascinated by his descriptions of unexplained—and sometimes bizarre—laboratory results. For example, if a very early duck embryo is cut into two parts, it becomes two separate embryos, but with an unusual twist: the rear half has the same head-to-tail orientation, but the front half has a random orientation.

Later Slack attended a lecture by the developmental biologist Lewis Wolpert and became hooked. Wolpert is famous for creating the theory of positional information, which essentially suggests that cells need instructions about their positions within the embryo before they can become differentiated cells. Slack got a fellowship to work in Wolpert’s lab and soon started doing experiments to learn more about how limbs grow and orient themselves in axolotls, a type of salamander.

His enthusiasm for this area of research sustains him to this day. One of his primary lines of investigation studies the regeneration of missing limbs and tails, primarily using Xenopus frogs and tadpoles as model organisms. In fact, it’s often the research he describes when non-scientists ask him about his work.

“It’s an obvious question that’s instantly interesting,” he explains. “Why can tadpoles regrow their limbs and humans can’t?”

Slack also studies the mechanisms of transdifferentiation, or the ways cells convert from one type into another. Recently, his lab developed methods for reprogramming certain liver cells into pancreatic cells—and vice versa—by introducing specific proteins. This line of research holds tremendous promise, as finding ways to generate insulin-producing pancreatic beta cells could lead to a new therapy for diabetics who must now rely on daily insulin injections or a limited supply of pancreas donors. It’s also an area ripe for collaboration with University of Minnesota researchers who are leading the way in improving islet-cell transplantation to treat diabetes.

The path ahead

As Slack settles in the Twin Cities, he will undoubtedly be asked, “Are you ready for Minnesota winters?” He brushes off the question with a shrug. After all, scientists are drawn to places that nourish their research interests and, as he explains, the University of Minnesota is one of those places—and more.

“I’m impressed with what the Medical School has already built,” he says. “The staff, the infrastructure—it’s all very big, and there’s a lot of good science going on here.” He sees the Stem Cell Institute as a place with a firm foundation built under the steady hand of his predecessor, Verfaillie, who is now leading the Stem Cell Institute in her native Leuven, Belgium, but continues to hold a 10-percent-time appointment at the University.

He also sees it on a path to become a world-class center capable of attracting the brightest minds and substantial research grants. He’s happy that Minnesota researchers are working with both adult and embryonic stem cells in order to maximize the avenues of promising work. And he expects to make the most of opportunities for clinical and commercial development.

Charles Moldow, M.D., the Medical School’s associate dean for research, thinks that Slack’s background is particularly suited to advancing the University’s stem cell initiatives. “His credibility as a developmental biologist permits easy entrée to our basic scientists, while the promise of cellular regeneration repair will attract clinicians.”

Powell also has full confidence in his abilities. “Jonathan Slack brings to our University his reputation as an outstanding developmental biologist, yet he never loses sight of the primary goal of advancing treatments and cures to improve lives. That makes him the right person to lead our Stem Cell Institute.” 

By Susan Cozzolino

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