From redefining cancer treatment to revolutionizing autism research, our newest researchers are pursuing the next wave of pediatric breakthroughs.
Each year, Seattle Children’s Research Institute recruits top researchers who can accelerate our quest to cure childhood diseases and disorders.
The five investigators profiled below have specialties ranging from cancer treatment to cell biology. But they cite the same reason for bringing their life’s work to Seattle Children’s: the chance to join forces with other top researchers who can help them solve some of medicine’s most vexing mysteries in ways that improve the lives of children throughout the world.
Dr. Surojit Sarkar – Helping immune cells stand guard against cancer
Dr. Surojit Sarkar is finding ways to help the immune system remember cancer and attack it if it relapses – whether that’s months or decades after a child’s cancer goes into remission.
“We can program T cells to kill cancer cells but those T cells tend to die off rapidly once the cancer is gone,” he says. “We want to instruct a handful of them to become memory cells that stay on the lookout and automatically deploy if the cancer comes back.”
Sarkar’s lab discovered that vitamin D and regulatory T cells put the brakes on killer T cells and help turn them into memory cells. Now he is investigating whether vitamin D supplements can spur lifelong immune memory to cancer in patients undergoing immunotherapy.
“We want the immune system to detect relapsed cancer and wipe it out long before it progresses to the point where a doctor can diagnose it,” Sarkar says.
Sarkar was previously at Penn State University and was drawn to Seattle Children’s – and our Ben Towne Center for Childhood Cancer Research – by the chance to make a real-world impact on cancer immunotherapies in children.
“In basic immunology, you can prove a lot of hypotheses and make elegant discoveries, but you’re always left guessing if they’re going to help cure diseases in people,” Sarkar says. “At Seattle Children’s, I can work directly with clinical scientists like Dr. Michael Jensen to quickly answer that question.”
Dr. Vandana Kalia – Breaking down cancer’s defenses
Dr. Vandana Kalia is uncovering how the immune system fends off disease, making insights that will help our researchers develop immunotherapies for many different types of cancer.
Immunotherapies, which use reprogrammed T cells to wipe out cancer cells, have been remarkably effective against some leukemia in clinical trials. But other cancers thwart the immune system. For example, some tumors send out signals that shut down immune cells.
“We’re looking inside T cells to understand how they respond to their environment and to cancer,” Kalia says. “That includes trying to figure out what is getting shut down and how we can turn it back on.”
Kalia’s lab discovered that a microRNA called miR-17~92 controls the size and duration of T-cell responses. Now she is studying ways to manipulate miR-17~92 and control T cells during immunotherapy.
Kalia, who was previously at Penn State University, came to our Ben Towne Center for Childhood Cancer Research because the center is able to quickly incorporate immunology discoveries into potential therapies.
“Seattle Children’s is one of very few places where immunologists work directly with the people who do the cell engineering, in a place that has its own cell production facility,” Kalia says. “That makes it much easier to apply our discoveries in ways that will hopefully help cure many different cancers.”
Dr. Stephen E.P. Smith – Pinpointing how autism affects the brain
Dr. Stephen E.P. Smith is looking for the biological links that explain what different forms of autism have in common and open the door to a new generation of treatments.
Researchers now believe that autism is not one disease, but a collection of hundreds of rare genetic diseases that cause similar symptoms.
“You can make an analogy to cancer, which is a bunch of diseases driven by different genes that do the same thing – they make cell division spin out of control,” Smith says. “We know that hundreds of gene alterations are associated with autism but very few patients have the same alterations. I’m looking for the thread that ties them together.”
Smith suspects this thread is hidden in the brain’s synapses. Each synapse contains a complex web of proteins that work together like tiny molecular machines. Many of the gene mutations linked to autism affect how these protein machines are built. Smith suspects this might explain why the brains of children with autism function differently than typical children’s brains.
Smith, who was previously at the Mayo Clinic, developed an innovative system – called quantitative multiplex immunoprecipitation – that maps out how proteins interact with each other in a synapse. Smith’s lab is using this system to pinpoint how different mutations affect the protein machinery at the glutamate synapse, which is where the brain processes and stores information.
This could help Smith understand which mutations cause the synapse to malfunction, affecting how children speak, play or interact socially. It could also help his team identify when different gene mutations have similar effects on the synapse and how it processes information.
It’s a step toward dividing patients with autism into groups based on how their gene mutations affect brain function.
“Our long-term vision is to categorize different types of autism so we can sequence patients’ genes and say ‘you have type two autism and we know which treatments work best compared to type one or type three,’” Smith says.
He was drawn to Seattle Children’s by the chance to work with other researchers – such as Seattle Children’s Raphael Bernier and the University of Washington’s Evan Eichler – who are at the forefront of studying how genes drive autism.
“I think this genetics-first approach is going to be the future of autism research and the best work in this area is coming out of Seattle,” Smith says.
Dr. Todd Cooper – Guiding leukemia therapies through clinical trials
Dr. Todd Cooper specializes in guiding innovative leukemia therapies through clinical trials and bringing them to children as quickly – and safely – as possible.
For instance, he’s leading a trial of CPX-351, a chemotherapy drug that’s designed to kill leukemia cells while minimizing heart damage and other side effects.
He’s also leading a Children’s Oncology Group effort to start a trial investigating whether personalizing treatment can improve outcomes for children with acute leukemia. The clinical trial will use genetic sequencing to identify the mutations that drive each trial participant’s cancer. Researchers will then match the patients with treatments known to be effective against cancer with those particular mutations.
“We want to see if this approach gives patients a better chance at being cured,” says Cooper, who joined Seattle Children’s from Children’s Healthcare of Atlanta, enticed by the opportunity to lead our clinical leukemia/lymphoma program and the chance to launch collaborations. He is already teaming up with investigators in our Ben Towne Center for Childhood Cancer Research and at Fred Hutchinson Cancer Research Center, and is working with Seattle Genetics and other companies to test new leukemia therapies.
“There are only a handful of places in the world that have such a high concentration of top-notch cancer researchers and companies that are testing innovative approaches to leukemia,” Cooper says.
Dr. Barry Gumbiner – Unraveling how cells bind together
Dr. Barry Gumbiner is illuminating how certain proteins – called cadherins and catenins – tell cells when to bind together and when to let go and move around.
This adhesion process helps build, maintain and regenerate tissue. But adhesion also malfunctions and lets cells invade parts of the body where they don’t belong.
Gumbiner’s latest research investigates ways to tighten the junctions between cells. This could prevent tumor cells from spreading and stop leaks in barriers like the lining of the gut and lungs. He also studies how cell junctions signal cells to tell them when to stop dividing, which is important for tissue regeneration and cancer growth.
“This work is still in the early stages, but it could lead to ways to stop cancer metastasis or prevent leaks associated with inflammation and sepsis,” Gumbiner says.
Gumbiner, who was previously at the University of Virginia, came to Seattle to work alongside world-class scientists and find new ways to apply his work to potential treatments.
“When I started looking at Seattle Children’s, I was struck by the quality of the researchers here – people like David Beier and Mark Majesky,” Gumbiner says. “I knew that being part of this community would inspire me and lead to critiques that make my work stronger.”
Seattle Children’s is one of very few places where immunologists work directly with the people who do the cell engineering, in a place that has its own cell production facility..
– Dr. Vandana Kalia