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Making Heart Surgery Obsolete

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Dr. Mark Majesky’s research could revolutionize treatments for everything from heart disease to muscular dystrophy.

Mark Majesky and Lisa Maves

The 2,000-square-foot zebrafish facility at Seattle Children’s Research Institute is the biggest in Seattle and has space for more than 3,000 tanks. Drs. Mark Majesky and Lisa Maves study zebrafish because the minnow-sized fish can regenerate damaged or defective tissue – and their transparent embryos allow researchers to monitor their development.

Think of Dr. Mark Majesky as a scientific detective, called in to solve one of biology’s most enduring mysteries.

Majesky is unraveling how stem cells transform into the vast array of specialized cells that build the body’s cardiovascular system. By understanding how everything (heart cells, brain cells and muscle cells) first forms, Majesky is moving a giant step closer to therapies that repair childhood disorders without surgery.

“We’re developing tools that could revolutionize how we treat heart defects, muscular dystrophy and many other serious conditions,” Majesky says. 

Stem cells to repair hearts

Zebrafish embryos

Zebrafish embryos are exciting to study because they are transparent and develop quickly.

The core of Majesky’s work is an initiative to develop stem cell treatments for heart problems. One in 100 children is born with a heart defect, and standard treatment can include open-heart surgery and sometimes even a heart transplant. Majesky wants to make these therapies obsolete by “reprogramming” a person’s own cells so they help the heart heal itself.

One of his projects aims to fix septal defects, which occur when a child is born with a hole in one of the heart’s walls. Majesky’s goal is to insert new genes into heart cells, instructing them to build tissue that closes the hole. His first step is to understand how stem cells make heart tissue, and why they don’t always do their job right.

“When you’re trying to regenerate an organ or part of an organ, sometimes the best clues come from how it was put together in the first place,” he says.

Majesky is particularly interested in knowing how blood vessels form. Such knowledge has implications that extend far beyond the heart. For instance, he is collaborating on a project that could lead to new cancer treatments.

“When you’re trying to regenerate an organ or part of an organ, sometimes the best clues come from how it was put together in the first place.”

Dr. Mark Majesky

The project builds on the work of European researchers, who found that the drug propanolol rapidly eliminates blood vessels in hemangiomas – tumors that appear on infants’ heads and necks. He is working with a team in hopes that understanding how the drug works will eventually lead to understanding how tumors grow blood vessels.

“If we can figure out how hemangiomas get their blood supply, we could potentially interrupt that process and stop tumors from growing or spreading,” Majesky says.

Building a dream team

Loie Robinson

Generous donations by Loie Robinson are helping Dr. Mark Majesky recruit top researchers and buy vital lab equipment to accelerate the process of discovery.

Majesky’s research is taking major steps forward thanks to Loie Robinson, a Seattle Children’s donor who was so inspired by Majesky’s work that she contributed $1.75 million to his research.

“Mark’s work has amazing potential to transform children’s lives, and I jumped at the opportunity to help speed up his progress,” Robinson says. 

Stem cell biology is so complicated that understanding it requires experts with different specialties. Robinson’s gifts are helping Majesky build a “dream team” that includes researchers like Dr. Lisa Maves, who investigates how different kinds of muscle cells – including the ones that drive the heart – develop. Maves left the Fred Hutchinson Cancer Research Center to work alongside Majesky. She hopes to make muscle cells invulnerable to muscular dystrophy, a condition that weakens people’s muscles until they stop working.

“There’s a tremendous need to cure this disease,” Maves says. “And Seattle Children’s has a unique group of clinical doctors and researchers who are working together toward that goal.”

Robinson’s donation also helped Majesky’s lab buy key equipment, including a $350,000 confocal microscope that can take time-lapse photos of stem cells from the moment they start developing. This helps researchers understand how stem cells function and how they can be manipulated to repair birth defects.

The Robinson–Majesky partnership highlights how private donations accelerate research that could ultimately save children’s lives around the world.

“Private donations provide critical seed money for innovative new projects,” Majesky says. “And that lets us generate the results we need to apply for larger grants.”

It’s all part of an “evolving revolution” in how heart defects are treated, according to Dr. Mark Lewin, co-director of Seattle Children’s Heart Center

“You can never be 100% sure, but I’m very confident that discoveries by Mark and our other biologists will translate into bedside treatments that improve children’s lives,” Lewin says. “And I think that’s going to happen in relatively short order.”

Published in Connection magazine, December 2012

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