Ever since she cloned a molecule early in her career, Linda Shapiro has had a mission: Figure out what it does.
So she spent years in the lab, explored its development, conferred with other researchers — anything to find the function of the molecule, known as CD13.
Now, after 20 years, Shapiro, a professor at the University of Connecticut Health Center, could be on the verge of a major breakthrough.
And if her theories are correct, scientists could use what they know of CD13 to improve on the body's own way of repairing itself after a heart attack, better guiding stem cells to the damaged heart — a process known as homing — and potentially improving a person's chances for recovery.
"If we could home stem cells to the damaged tissue, this would be a huge area of therapy," said Marc Lalande, director of UConn's Stem Cell Institute.
Heart attacks were not an immediately obvious idea for CD13. Instead, Shapiro spent years learning about other functions of the molecule, exploring aspects such as what controls its expression and what role it plays when a cell's fate is determined.
Then, nine years ago, she learned from another researcher that CD13 played an important role in getting drugs meant for tumors delivered to the proper place. CD13 showed up on the tumors in newly formed blood vessels, so Shapiro began exploring why.
A cardiologist she spoke with at a meeting offered a suggestion: After a heart attack, the body forms new blood vessels to get past the blockage. Why not look into whether CD13 shows up when that happens?
She did, and found that CD13 shows up in force on the new blood vessels that form.
That may have something to do with what happens to the body after an injury.
When a person is injured, the body sends cells to the site of the injury to protect it. In a heart attack, for example, the body sends stem cells to begin repairing the damaged tissue. If that process doesn't work well enough, the person can develop heart failure.
But the repair cells need a way to know where to go, and Shapiro thinks that's where CD13 comes in: It may serve as a sort of address for the body's internal emergency responders to know where to go.
What happens without CD13? Shapiro and Dr. Bruce Liang, the chief of UConn's cardiology division, are testing that question using mice who have been bred without CD13. In their lab, researchers induce heart attacks in those mice and mice that have CD13, then compare the results.
About 80 percent of the mice in both groups survive, but those without CD13 end up with markedly poorer heart function. "It just seems that without CD13, the function is impaired," Shapiro said.
Stem cells, which the body sends to the heart to repair it, already have some CD13 on them. Shapiro thinks that adding more CD13 to stem cells could help make sure they get to the proper place. Earlier this year, she received a grant from the state — part of a 10-year, $100 million Connecticut program to fund stem cell research — to test that theory. She will treat stem cells with a material that will produce more CD13, then examine whether it makes them more likely to stick to a site of injury.
Ultimately, her work could lead to the development of a way to inject CD13-fortified stem cells into the arm of a person who had a heart attack, boosting the body's natural response. It could potentially be applied to other types of disease or injuries.
Of course, like much of the work on stem cells, that may be years away, if it proves possible at all. But after two decades, Shapiro has hopes for what CD13 could accomplish.
Copyright © 2009, The Hartford Courant