Making Heart Surgery Obsolete

Dr. Mark Majesky’s research could revolutionize treatments foreverything 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 transparentembryos allow researchers to monitor their development.

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

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

“We’re developing tools that could revolutionize howwe treat heart defects, muscular dystrophy and manyother serious conditions,” Majesky says.

Stem cells to repair hearts

Zebrafish embryos

Zebrafish embryos areexciting to study becausethey are transparent anddevelop quickly.

The core of Majesky’s work is an initiative to develop stemcell treatments for heart problems. One in 100 children isborn with a heart defect, and standard treatment can includeopen-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 heartheal itself.

One of his projects aims to fix septal defects, which occurwhen 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. Hisfirst step is to understand how stem cells make hearttissue, and why they don’t always do their job right.

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

Majesky is particularly interested in knowing how bloodvessels form. Such knowledge has implications that extendfar beyond the heart. For instance, he is collaborating on aproject that could lead to new cancer treatments.

“When you’re trying to regenerate an organ or part ofan organ, sometimes the best clues come from how it wasput 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 bloodvessels in hemangiomas – tumors that appear on infants’heads and necks. He is working with a team in hopes thatunderstanding how the drug works will eventually lead tounderstanding how tumors grow blood vessels.

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

Building a dream team

Loie Robinson

Generous donations by Loie Robinson are helping Dr. Mark Majesky recruittop researchers and buy vital lab equipment to accelerate the processof discovery.

Majesky’s research is taking major steps forward thanksto Loie Robinson, a Seattle Children’s donor who was soinspired by Majesky’s work that she contributed $1.75 millionto his research.

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

Stem cell biology is so complicated that understandingit requires experts with different specialties. Robinson’sgifts are helping Majesky build a “dream team” that includesresearchers like Dr. Lisa Maves, who investigates howdifferent kinds of muscle cells – including the ones thatdrive the heart – develop. Maves left the Fred HutchinsonCancer Research Center to work alongside Majesky. Shehopes to make muscle cells invulnerable to musculardystrophy, a condition that weakens people’s musclesuntil they stop working.

“There’s a tremendous need to cure this disease,” Mavessays. “And Seattle Children’s has a unique group of clinicaldoctors and researchers who are working together towardthat goal.”

Robinson’s donation also helped Majesky’s lab buy keyequipment, including a $350,000 confocal microscope thatcan take time-lapse photos of stem cells from the momentthey start developing. This helps researchers understandhow stem cells function and how they can be manipulatedto repair birth defects.

The Robinson–Majesky partnership highlights how privatedonations accelerate research that could ultimately savechildren’s lives around the world.

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

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

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

Published in Connection magazine, December 2012