Scottish 'fighter' hosts next Science Cafe

Stephen Duncan wants to give children with rare liver diseases something that’s often in short supply for them: hope. “Somebody needs to be in their corner fighting for them, because not everything has to make money.”

That determination to help this neglected group of patients will be on display at the April 27 Science Cafe at 5:30 p.m. at Charleston Beer Works. Duncan, chairman of the Regenerative Medicine and Cell Biology Department at the Medical University of Carolina, will give a talk titled “Stem cells: The great pretenders.”

Duncan, who holds a doctorate from Oxford University and still speaks with the accent of his native Scotland, said a lot of people have heard about stem cells but most don’t know about the impact they can have when it comes to finding new treatments for disease. “In my Science Café talk, I’d really like to highlight how powerful this is going to be for personalized medicine.”

And personalized medicine is key when it comes to treating diseases that don’t affect many people, Duncan said. “The amount of money it would take to develop a drug to treat a rare disease using standard approaches is astronomical. There’s not enough of a market for it. However, in an academic setting, it’s actually feasible for us because we’re not in the business of trying to make huge amounts of money out of it.”

But Duncan, SmartState chairman in regenerative medicine, is not developing new drugs. His team focuses on using existing drugs in new ways. The process starts in the lab. 

“Basically, we can take some cells from any individual. It can be a skin punch biopsy, it can be blood draw, a urine sample, even a pluck of hair, and turn these cells into the equivalent of embryonic stem cells, but they really come from an adult person,” Duncan said.

Those stem cells can be incredibly powerful, able to develop into a range of cell types, whether in the body or in a laboratory such as Duncan’s.

“Let’s say you have liver disease,” Duncan said. “We can take a skin cell biopsy. We can turn these into stem cells and then make your liver cells in a culture dish. So we can recreate a patient’s  liver disease in the laboratory. That allows us to study the disease, but more importantly allows us to start looking for drugs that can be used to reverse that disease in the lab.”

That search brings him and his team to “libraries” of drugs already on the market. They look for medications with beneficial side effects. For example, they zeroed in on a class of heart failure drugs called cardiac glycosides, already on the market, that cause the heart to contract more efficiently.

Duncan and his team noticed something unusual about those drugs: They had the unintended effect of lowering cholesterol. They knew that might be the breakthrough they were looking for in their fight to treat the genetic disorder familial hypercholesterolemia.

“This is a disease that causes permutations that prevent the liver from clearing bad cholesterol,” Duncan said. “So children and ultimately adults with mutations in this gene end up having huge levels of bad cholesterol. Untreated, they end up getting cardiovascular disease because there’s so much lipid in the bloodstream. Their bad cholesterol level may soar to 10 to 15 times the normal level.”

Statins are the usual treatment, but not everyone can tolerate them. Now, armed with the knowledge that cardiac glycosides may be an alternative, Duncan has been testing the heart failure drugs in stem cells to see if they can be tweaked to be used safely in people with this condition.

“One of the problems with the drugs, we found, is they’re difficult to work with. They’re not like statins. At very high levels, they’re toxic, because they’re affecting the heart, and when levels are too low, they’re not effective at all. Karen Lackey and I have been looking at how we can target these to the liver.” 

That collaboration with Karen Lackey, who directs the South Carolina Center for Therapeutic Discovery and Development at MUSC, is a sign of Duncan’s interest in including new voices from different areas in his lab’s work. He came to MUSC less than a year ago from the University of Wisconsin, and he hasn’t wasted any time in gently reshaping his department.

“I really want to try to diversify,” Duncan said. “My basic interest is using cell biology to treat human diseases. That’s where I want to see the department go.”

He’s recruiting people from around the world to join his team, bringing in at least five new faculty members. “We’re working in different areas,” Duncan said. “We’re interested in digestive disease, which includes liver and pancreas and GI (gastrointestinal)."

We’re also trying to put together a bigger initiative that pairs our department with physician scientists in the Department of Medicine and Hollings Cancer Center, because cell biology is a crucial part of understanding cancer.”

Duncan is fascinated by the possibilities as he looks to the future in his field of research. “The second big wave is trying to make neurons and neural-related cells to treat things like Parkinson’s and Huntington’s and Lou Gehrig’s disease. A lot of work has been done in that area. It’s one of the big focuses of the community.”

Duncan said he’s pleased to be at MUSC, although it’s a long way from Glasgow, where he grew up. He wound up in the U.S. after meeting and falling in love with an American, Paula Traktman, Ph.D. They lived in Manhattan, moved to Milwaukee to raise their kids and now call Charleston home. Traktman is dean of the College of Graduate Studies at MUSC.

Duncan has noticed some similarities between where he is now and his home country. “Scots and South Carolinians both have a penchant for fried food,” he said, laughing. 

The Charleston Beer Works may be a good fit for his Science Cafe talk, then, with fried pickles and fried cheese on the menu. Duncan is sure to add spice to the evening as he talks about work that he sees as critically important. 

“I do get really frustrated that out of all this information we’ve collected out of the last 50 years that we’re not seeing help for kids particularly that are affected by these rare diseases.”

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The April 27 Science Cafe, "Stem Cells: The Great Pretenders," will be at Charleston Beer Works starting at 5:30 p.m. It's open to anybody who wants to learn about science in a fun, informal atmosphere.