From curing graft-versus-host disease to using Facebook to prevent drunk driving, Seattle Children's Research Institute's newest researchers are pursuing innovative solutions to seemingly intractable problems.
The eight investigators profiled here could have taken their labs almost anywhere – but chose Seattle Children’s Research Institute as the best place to pursue discoveries that improve children’s lives. They pointed to the research institute’s collaborative culture – and its commitment to developing real-world therapies – as what set it apart.
“The research institute is divided into nine centers but, once you step inside, boundaries disappear and everyone works together,” says Dr. David Beier, who came to Seattle Children’s from Harvard Medical School.
This collaborative culture is something that Dr. Jim Hendricks, research institute president, strives to maintain.
“Collaboration accelerates the search for cures,” Hendricks says. “I don’t think you can survive in science today if you’re not focused on interdisciplinary research.”
David Beier – using technology to pursue next-generation cures
In the 1990s, it took eight years for Dr. David Beier ’s team to identify genes that cause polycystic kidney disease. Today, that gene discovery process would take only months, thanks to new sequencing technologies.
Beier came to Seattle because it offered a chance to be at the forefront of this revolution, in a place he considers home – he received his medical degree and his doctorate from the University of Washington and completed a pediatrics internship at Seattle Children’s.
Now, as director of the Center for Developmental Biology and Regenerative Medicine, one of Beier’s goals is to build a state-of-the-art bioinformatics program that helps researchers sift through vast amounts of data and identify the information that matters.
“Some of the world’s leading technology companies are literally just down the street from us,” Beier says. “I’m excited to partner with them on technologies that illuminate the path toward cures.”
Richard James – investigating how cells become disregulated
Dr. Richard James studies how cellular signaling pathways govern whether cells behave normally or veer off track to become cancerous or attack healthy tissue.
“We’re trying to understand how cells become disregulated – and how we can stop that or treat it,” says James, who came to Seattle Children’s from the University of Washington.
James and his colleagues recently identified lymphoma cell pathways that are upregulated when treated with the drug ibrutinib. This promotes drug resistance by enabling those cells to work around the drug. Now James’ team is investigating whether combining ibrutinib with other drugs can halt that resistance.
“At other institutions, we might be doing this research just for the sake of understanding pathways,” James said. “Working at Children’s puts me alongside clinicians who treat these diseases every day, and we’re working together to solve real clinical problems they run into.”
Franck Kalume – tracing the path from gene to seizure
Dr. Franck Kalume is unraveling why severe epileptic seizures sometimes cause sudden, unexpected death in children and adults.
Kalume, who was previously at the University of Washington, and his colleagues use mouse models of genetic epilepsies to study how gene mutations lead to seizures and related neurological disorders. The researchers recently found that seizures cause sudden death by triggering excessive activity in the vagus nerve. This causes a dramatic slowing of the heart in a severe form of epilepsy called Dravet syndrome.
Now Kalume’s team is investigating new treatments that could prevent this, such as pacemakers that stop the heart from slowing during seizures. Kalume is also studying therapies that suppress vagus nerve activity.
“My research involves multiple disciplines and I wanted to go somewhere I could collaborate with experts in many areas,” Kalume says. “At Children’s that collaboration is easier than at many other institutions.”
Leslie Kean – pursuing new treatments for graft-versus-host disease
Dr. Leslie Kean came to Seattle Children’s to save children from graft-versus-host disease (GVHD) and other debilitating effects of bone marrow transplantations.
GVHD is one of the two most common causes of death for transplant patients (the other is cancer relapse). Kean joined Seattle Children’s from Emory University, where her team found that a rheumatoid arthritis drug could potentially eliminate GVHD. Now, as associate director of the Ben Towne Center for Childhood Cancer Research, she is leading a Phase 2 clinical trial to evaluate whether the drug is effective in children. This multicenter study is the only one in the nation aimed at preventing pediatric GVHD.
One of Kean’s long-term goals is to genetically engineer a type of T cell, called regulatory T cells, in a way that ensures transplant patients don’t get GVHD. These engineered cells could also be used to treat patients with type 1 diabetes, Crohn’s disease and other autoimmune diseases. Kean will be collaborating with Ben Towne Center Director Dr. Michael Jensen on this project.
“Seattle is the epicenter of transplant and T-cell research,” Kean says. “To be here is a dream come true.”
Jason Mendoza – working to prevent childhood obesity
When Dr. Jason Mendoza received a job offer from Seattle Children’s, he jumped at the chance to return to the place he did his residency – and to emulate the clinician-researchers who guided him through it.
“I was mentored by doctors who didn’t just hear about advances – they tried to push their fields forward,” Mendoza says.
Mendoza’s research looks back to eras when obesity was uncommon for clues on how to prevent it in children today. Forty years ago, almost half of U.S. children walked or rode their bikes to school, but most kids today get a ride from their parents or take a school bus.
Mendoza investigates whether “walking school buses” and “bicycle train” programs where adults supervise groups of kids as they walk or bike to school can help kids be physically active and thereby maintain healthy body weights – especially in low-income areas where obesity rates are highest. If Mendoza finds that these programs are effective, it could convince school districts and other organizations to oversee them in more areas.
“There isn’t one magic solution to childhood obesity,” says Mendoza, who joined Children’s from Baylor College of Medicine. “It’s going to take changes in a bunch of different areas, from how kids get to school, to how they eat, to how we design our cities.”
Megan Moreno – using Facebook to identify substance abuse
Dr. Megan Moreno investigates innovative ways that technology can help adolescents overcome health and behavior challenges.
She launched some of the first research on how Facebook can help identify when adolescents engage in risky alcohol or drug use. One of her core studies, which she co-leads with Dr. Dimitri Christakis, tracks Facebook posts by 300 college students who volunteered to participate. When a participant’s posts refer to risky behaviors – like drinking and driving – Moreno’s team offers to do an assessment and connect the student with counseling or other resources when needed.
“Facebook lets us keep track of risky behavior in real time and step in a lot earlier than we might otherwise be able to,” Moreno says.
Moreno grew up in the Seattle area and completed a fellowship in adolescent medicine at Seattle Children’s Hospital. Returning here from the University of Wisconsin meant coming home and having a chance to partner with researchers who have similar interests to hers. For instance, she recently launched a study to develop a standard definition of cyberbullying, in partnership with collaborators from the University of Washington, the Washington office of Superintendent of Public Instruction and other local groups.
“We’re diversifying into new areas and we’ve had five grants funded in 2013,” Moreno says. “I think that success is a direct result of being able to build collaborations with people at Children’s, the University of Washington and throughout this area.”
Albert Quintana – developing innovative treatments for mitochondrial disease
Dr. Albert Quintana investigates why a select group of neurons survive when mitochondrial disease robs them of energy.
“If we can figure out what mechanism lets those neurons persist while the ones around them die, it might lead to a new treatment or cure,” Quintana says.
Quintana came to Seattle Children’s from the University of Washington. He and his colleagues used one of the first mouse models of mitochondrial disease to find that the mTOR pathway, which signals neurons to spend their energy on survival or on growth, was defective in these mice. The researchers were able to alleviate mitochondrial disease by using an FDA-approved drug to block this pathway in a mouse model of Leigh syndrome, a genetic neurological disorder that usually strikes during infancy. Quintana’s lab is now defining how blocking mTOR helps neurons survive and is testing new drugs to see if they could be effective against mitochondrial disease.
“If I worked at a more traditional academic institution, I would make discoveries and wait for someone else to turn them into therapies,” says Quintana. “Children’s gives me the opportunity to be involved in that translational process.”
Davene Wright – finding cost-effective interventions
Dr. Davene Wright builds simulation models that help Seattle Children’s researchers identify which interventions are most cost effective.
She modeled obesity interventions as a doctoral student at Harvard University, and was drawn to Children’s by the opportunity to work alongside some of the nation’s top childhood obesity researchers: Drs.Brian Saelens, Pooja Tandon and Jason Mendoza.
Traditionally, obesity interventions can be expensive. Wright compares the cost of new potential therapies with the long-term cost of treating a patient – a calculation that is particularly important with obesity since it increases a child’s risk of eventually suffering everything from asthma to heart attacks to cancer.
“Childrens’ researchers are developing innovative ways to prevent obesity,” Wright says, “and I’m excited to help them make the business case for those interventions.”