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Research on the Rise

Significant Recruits of 2010

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2010 was a banner year for recruiting at Seattle Children’s Research Institute as several nationally recognized researchers chose to continue their life’s work in Seattle.

The seven scientists profiled below unanimously cited the culture of collaboration – both within Children’s and with other well-respected research powerhouses in the region – among their top reasons for relocating their labs and lives.

“A multidisciplinary approach is what defines most research today,” says Dr. Jim Hendricks, president of Seattle Children’s Research Institute. “Fundamentally, scientists will successfully collaborate with other scientists whenever possible. What distinguishes Seattle and the Northwest is the collaborative environment among institutions, which removes barriers that can get in the way of a scientist’s work.”

The institute acts as an organizing platform that generates discussion and interaction among basic scientists, clinicians and even patients.

“Investigators used to work in silos, but now there’s so much cross-fertilization,” says nephrologist Dr. Allison Eddy, who leads the institute’s Center for Tissue and Cell Sciences. “In the era of genetics and molecular and cell biology, the work on one organ is often relevant to the work on another. If you can understand a system in one part of the body, there may be a lot that is relevant to another part of the body.”

Meet seven research powerhouses who now call Children’s home and find out what they are working on.

Dr. Mike Jensen – reprogramming the immune system to fight cancer

Jensen 220x130 A pediatric cancer specialist and immunologist, Dr. Mike Jensen is closing in on his goal of getting an individual’s own immune system to attack and kill cancer just like it would the common cold – an approach that would end the devastating side effects caused by therapies like chemotherapy and radiation.

"We're creating a type of therapy that could only be possible by putting our research and technologies together." ~Dr. Mike Jensen

He and his team are working on reprogramming the T-cells of patients with cancer in a way that instructs them to attach to cancer cells and wipe them out as they would an infection.

Previous experiments with mice have shown that these genetically modified T-cells can eradicate cancer in just a few days with minimal flu-like side effects. Initial results of Phase I clinical trials show promising safety in humans. Jensen’s team is preparing to take the next critical step of testing T-cell therapies in children; the Seattle Children’s Research Institute is constructing a cutting-edge, $5 million cell-production facility where Jensen’s team will reprogram cells for use in clinical trials to be conducted at Seattle Children’s Hospital.

“Seattle is growing into a major scientific community for immunotherapy,” says Jensen, who completed his fellowship in pediatric hematology/oncology at the University of Washington and the Fred Hutchinson Cancer Research Center.

“I have really long-term collaborations with great scientists in Seattle, particularly with Dr. Stan Riddell at the Hutch, who has identified a type of T-cell that has the special ability to last for a long time in the body. We’re taking the T-cells Stan discovered with my genetic reengineering to create the cancer-fighting T-cells. We’re creating a type of therapy that could only be possible by putting our research and technologies together.”

  

Dr. William Dobyns – unlocking the genetic basis for brain disorders 

Dobyns 220 x130 Dr. William Dobyns joined Children’s from the University of Chicago, bringing more than 25 years of expertise on the nature and genetic basis of developmental brain disorders.

My goal is to provide as much definitive information as I can about developmental brain disorders and the links between seemingly distinct disorders so that medical science can begin to impact clinical care." ~Dr. William Dobyns

Having spent his career studying both common and extremely rare abnormalities, Dobyns is able to diagnose complicated patients when few others can.

“A correct diagnosis answers the parents’ first question: ‘what’s wrong with my child?’” he says. “Then we can begin to talk about what they can expect, how to make a difference, why it happened and whether it will happen again.”

His research interests were sparked in the clinic when he noticed that patients with autism, for example, also had birth defects of the cerebellum and a history of infantile epilepsy.

“My goal is to provide as much definitive information as I can about developmental brain disorders and the links between seemingly distinct disorders so that medical science can begin to impact clinical care,” he says.

Dobyns notes that collaboration and shared resources are critical to advancing medical science, as are institutional vision and commitment.

“Advancing a body of work like this requires professor-level expertise in four or five areas of science, medicine and technology, which no one person can have. The colleagues here from Children’s and the University of Washington, along with the superior brain imaging technology, expose the work I’ve done to new ideas, new bodies of knowledge, new resources and new expertise.”

Not only is the possibility here, but the willingness to collaborate is supported and encouraged. “There’s an energy at Children’s that seems lacking elsewhere,” he says.

 

Dr. Kathleen Millen – identifying the genes that cause brain malformations

Millen 220x130Dr. Kathleen Millen came to Seattle from Chicago to continue her work with Dr. William Dobyns. Their research on the genetic basis of early brain development combines Millen’s expertise on the mouse brain with Dobyns’ extensive knowledge of human brain abnormalities.

I believe we will make significant progress in understanding brain development - specifically the cerebellum - from embryonic beginnings to final structure and function in the foreseeable future. ~Dr. Kathleen Millen

“Because the genetics of mouse and human brains are very similar, we can identify a gene that causes a malformation in human patients and then look at the corresponding gene in mice to understand how development was disrupted,” says Millen. “We can also identify mouse malformation genes and determine if they are altered in human patients.”

Millen’s work carries considerable implications for a patient’s diagnosis and prognosis. She primarily studies birth defects of the cerebellum. The Millen-Dobyns collaboration identified the first genes involved in the Dandy-Walker malformation, the most common structural defect in the human cerebellum, which affects one in 5,000 births and often causes significant intellectual and motor delays. Hydrocephalus is also a common mark of this malformation.

Most cases of Dandy-Walker are diagnosed in utero by ultrasound at 15 to 18 weeks. However, even when the brain malformation is obvious, there is a 30% to 40% chance that the infant could be only mildly affected unless another birth defect is present. Current imaging techniques cannot help determine what distinguishes mildly from severely affected babies. But genetics will.

“The scientific community in Seattle has so much expertise that its gravitational pull is strong,” says Millen, of her choice to continue her research here. “The UW has one of the world’s best genome research centers and the Center for Integrative Brain Research at Seattle Children’s has an exciting collaborative environment. I believe we will make significant progress in understanding brain development – specifically the cerebellum – from embryonic beginnings to final structure and function in the foreseeable future.”

Dr. Tamara Simon – lowering the risk of repeated shunt infections

 Simon 220x130Dr. Tamara Simon is working to lower the risk of repeat cerebrospinal fluid (CSF) shunt infections in patients with hydrocephalus.

The treatment for CSF shunt infections is very invasive – patients undergo surgery either to remove or externalize the infected shunt, and an external ventricular drain is placed inside their skulls to drain CSF. Children then remain in the hospital for two to three weeks with the drain in place as they are treated with intravenous antibiotics to eliminate the infection. Finally, patients undergo another surgery to implant a new shunt.

About 20% to 25% of these patients return to the hospital with a new infection, usually within six months.

“Clearly, we don’t yet have the right tools in our arsenal to prevent subsequent infections,” says Simon, a pediatric hospitalist who was recruited to Seattle Children’s from the University of Utah.

Simon has an ongoing, multicenter study in the Hydrocephalus Clinical Research Network looking at the treatment of CSF shunt infections at Seattle Children’s and four other pediatric centers. By assessing the wide variation in treatment approaches, Simon hopes to identify those that are most effective at preventing reinfection.

In addition, she is working to develop a biomarker of bacterial load based on the 16S rRNA gene, which is present in all bacteria. She is testing infected samples of CSF to see if a new 16S assay can be used to track a patient’s response to antibiotic therapy. If the assay is able to demonstrate a response to therapy, it may also help distinguish which patients go on to develop a repeat infection. If it’s successful at both, the assay may ultimately become a tool clinicians can use to help decide how long patients with infected shunts should stay on antibiotic therapy before a new shunt is implanted.

By assessing the wide variation in treatment approaches, Dr. Tamara Simon hopes to identify those that are most effective at preventing repeat cerebrospinal fluid shunt infections.

 

Dr. Rachel Katzenellenbogen – investigating how viruses disrupt cells

Katzenellenbogen 220x130As a clinician, Dr. Rachel Katzenellenbogen wants to help her patients and their families understand the risk of sexually transmitted diseases, like human papillomavirus (HPV), so that they can make appropriate decisions. As a scientist, she wants to understand the underlying mechanisms that make these diseases harmful so she can provide the best guidance possible.

She wants to know why, for example, 99% of all cervical cancers are correlated with HPV even though only a small percentage of people exposed to HPV ever develop the cancer. Her research currently focuses on the role HPV protein E6 plays in making HPV necessary for, but not sufficiently causal in, the development of cervical cancer.

An adolescent medicine doctor who completed her residency at Seattle Children’s and her fellowship at the UW, Katzenellenbogen found motivation to stay in Seattle from her fellow residents, her research mentors like Drs. Denise Galloway and Arnold Smith, and collaborators from the University of Washington, the Department of Public Health and Fred Hutchinson Cancer Research Center.

The balance between general pediatrics and subspecialty care at Children’s enables her to integrate her adolescent medicine practice with her interest in infectious disease and hematology/oncology research.

“I see a hopeful end for my work,” Katzenellenbogen says. “Understanding how the disruption to a cell caused by HPV makes the cell more likely to become cancer may become a model for understanding how other tumor viruses can lead to cancer.”

 

Dr. Eric Turner – transcription factors and brainstem development

Turner 220 x130Dr. Eric Turner returned to his native Seattle to continue his research on brain development at the Center for Integrative Brain Research at the Seattle Children’s

Research Institute, where he is able to integrate his work in developmental biology and his interest in neuroscience.

At the Seattle Children's Research Institute, you can go next door or up or down a floor and find investigators to participate on the kind of team you need." ~Dr. Eric Turner

“Designing experiments and integrating methods takes expertise in everything from molecular genetics to electrophysiology to behavioral science,” Turner says. “It can’t be done by one person; it has to be a team. At the research institute, you can go next door or up or down a floor and find investigators to participate on this kind of team.”

Turner has focused on the pivotal role transcription factors play in brainstem development and sensory function. One of these factors is important in the development of facial structures and can cause visual impairment and facial deformities in children with defects in this gene. A collaboration with Drs. Michael Cunningham and Tim Cox of Seattle Children’s Craniofacial Center will enable Turner and his team to use cutting-edge imaging technology to follow the development of neurons and facial structures in time and space.

Another project that received a big boost from Turner’s move to Seattle is a collaboration with the local Allen Brain Institute on “optogenetic” mice, in which brain activity can be controlled by light. Turner plans to use these mice in studies of the habenula, a region of the brain thought to play a role in attention, memory, mood and the regulation of basic drives and addictions. Ultimately, optogenetic methods may be used to explore the functions of genes linked to conditions like autism and schizophrenia.

Dr. Tonya Palermo – developing online tools for chronic pain management

Palermo 220x130Dr. Tonya Palermo smiles at the irony. Although her research has involved using technology to treat chronic pain, she didn’t even own a cell phone until a few years ago. “It’s funny because I’m not a tech person at all,” she says, “but it’s exciting to see the potential reach of technology in helping children cope with this condition.”

Palermo, a psychologist specializing in pain management, left Oregon Health & Sciences University to join the pain medicine program at Seattle Children’s in August. “I came here to expand the impact of my research at a world-class institution that has outstanding investigators in both pediatric behavioral research and a strong pain medicine program,” she says. “The potential to partner with investigators on the use of technology to reduce suffering in children with chronic pain was very attractive.”

Palermo has made it her life’s work to study psychological treatment for chronic pain, including cognitive behavioral strategies that teach children skills (such as relaxation and positive thinking) for managing their pain and increasing their level of activity. After successfully completing a small trial, she recently launched a five-year study exploring whether children can learn cognitive behavioral strategies over the Internet to reduce chronic pain and improve their ability to function.

It’s the largest pediatric chronic pain study undertaken to date and it could open the door for more children to have effective behavioral pain interventions at home, which would reduce the substantial barriers faced by families when trying to find effective treatment for chronic pain in their local communities.

Palermo also plans to work with sleep researchers at the University of Washington to dig deeper into the relationship between insomnia and chronic pain. She hopes to leverage other UW resources, such as a twin registry and large epidemiological studies, to gain additional insights into the risk factors for chronic pain. “There are great opportunities at the UW and Children’s to work toward prevention and treatment of pediatric chronic pain.”