An academic medical center and research institute, Seattle Children’s is dedicated to helping junior faculty establish research careers. Recently, several of our emerging genetics researchers have made significant contributions to their field.

Bamshad 220x130 "The Seattle area has one of the highest concentrations of geneticists in the world,” notes Dr. Mike Bamshad, professor of pediatrics at the University of Washington (UW), and director of Seattle Children’s Research Institute’s Center for Genetics and Development. "There are phenomenal strengths across many facets of human genetics research, including technology development, clinical genetics and translational therapeutics."

The culture of collaboration across departments and schools at the UW and even institutions throughout Seattle contributes to the junior faculty’s success. So does senior faculty’s commitment to fostering their careers.

“When we’re recruiting we look at the scope and the quality of someone’s science and assess how novel it is, how productive they are and whether they can bring a new facet to the work being done here,” says Bamshad. “They also have to be passionate about the questions they are asking. The climate nowadays is so competitive, and resources so limited, that if someone isn’t passionate their chances for success are diminished.”

Below you’ll meet four faculty members who are on their way to becoming national leaders in their respective areas and are establishing their careers at Children’s and the University of Washington.

Dr. Dan Doherty – contributing to the understanding of ciliopathies

Even 10 years ago, the primary cilium was thought to be a vestigial part of the cell without and important function. Now we know that cilia function as antennae for almost every cell in the body." ~Dr. Dan Doherty

Doherty 220x130Dr. Dan Doherty investigates the genetics of human hindbrain malformations, particularly Joubert syndrome. His lab identified four of the 10 genes known to

cause Joubert syndrome, accounting for 50% of patients who have this genetic condition. Identifying these genes provides a more definitive diagnosis, clearer information about the health and developmental challenges people with this condition can anticipate, and the option for carrier and/or prenatal testing.

The genes responsible for Joubert syndrome function in a cellular structure called the primary cilium, making Joubert syndrome one of an expanding group of disorders called “ciliopathies.” In total, the ciliopathies affect about one in 500 people, causing a variety of overlapping clinical features in different patients including intellectual disability, retinal disease, kidney failure, liver fibrosis, obesity, skeletal abnormalities and polydactyly.

“Even 10 years ago, the primary cilium was thought to be a vestigial part of the cell without an important function. Now we know that cilia function as antennae for almost every cell in the body, allowing cells to sense fluid flow, light and smells, as well as interpret messages sent by other cells to coordinate development. Cilium research is an amazing and relatively unanticipated new field of biology,” says Doherty. “We anticipate that understanding cilium dysfunction in relatively rare disorders will improve our understanding of more common disorders of the brain, retina, kidney and other organs, eventually leading to improved treatments.”

In clinic Doherty cares for children with hindbrain malformations, like Joubert syndrome, and he counsels pregnant women carrying fetuses with central nervous system abnormalities such as hydrocephalus, spina bifida and brain malformations.

“The field of human genetics is now moving so rapidly that I get to see the impact of my research when I am able to tell a family the genetic cause of their child’s disorder,” Doherty says. “It’s a physician-scientist’s dream to take a problem from the clinic into the lab and then use the research results to help their patients.”

Dr. Heather Mefford – investigating genetic pathways

Mefford 220x130Dr. Heather Mefford is identifying genetic causes for pediatric disorders, including epilepsy, intellectual disability and birth defects. Her goal is to help biomedical scientists understand genetic pathways and the disruptions that cause disease.

She uses state-of-the-art technology, like array CGH, to discover and characterize new genomic disorders, including deletions of chromosomes 1q21, 15q13 and 17q12. People missing these chromosome segments are at risk for intellectual disabilities, autism and epilepsy, suggesting a common genetic link between these disorders.

The patient population at Seattle Children’s enables Mefford to see significant numbers of complicated patients with neurodevelopmental and genetic disorders. The discoveries she has made can provide more definitive diagnoses and prognoses for the patients and families she works with in the Genetics Clinic at Seattle Children’s Hospital.

“The clinical component of my work makes my research more meaningful,” says Mefford, who spends about 80% of her time doing research. “Seeing patients and families makes it clear that having a certain diagnosis, even though it doesn’t yet change the treatment or the outcome, is helpful for families. It inspires me to get better information to the clinic sooner.”

“Geneticists are driven to understand the genetic basis of disease because we believe this information will lead us to better treatments and cures. I am fortunate to interact with a great group of researchers in Seattle who are using technology to understand disease. The scientists and physicians I work with are very innovative and collaborative, which creates an inspiring, fun and successful working environment.”

Dr. Heather Mefford has used state-of-the-art technology, like array CGH, to discover and characterize several new genomic disorders, including deletions of chromosomes 1q21, 15q13, and 17q12.

Dr. Holly Tabor – investigating issues raised by the genome revolutionTabor 220 x130

A history of science major as an undergrad, Dr. Holly Tabor has long been interested in issues that live in the intersection between science and society. Tabor, a bioethicist originally trained in genetic epidemiology, joined the Treuman Katz Center for Pediatric Bioethics from the Stanford Center of Biomedical Ethics.

These new genetic sequencing approaches radically change the amount of information we may learn about participants in pediatric genetic research." ~Dr. Holly Tabor

She collaborates with Bamshad at the Center for Clinical Genomics as the “integrated ethicist” on a number of genetic projects.

Her current research focuses on ethical challenges in new kinds of genetic research called exome and whole genome sequencing. These new approaches sequence all of the genes in the genome, and can identify all the possible genetic changes that might cause or increase risk of disease in a person. This might include genetic changes that are unrelated to the primary disease or condition being studied.

“These new sequencing research approaches radically change the amount of information we may learn about participants in pediatric genetic research,” Tabor says. “This includes information about known genetic causes of both pediatric and adult diseases, as well as a lot of genetic information about an individual that we still don’t know how to analyze or interpret.”

Tabor is investigating how researchers should decide what information can and should be returned to research participants. She is also studying the best way to convey and explain these kinds of results, and the health and psychological impacts of the information. Together with Bamshad, she is developing tools to explain the benefits and risks of this kind of research to participants in the informed consent process.

“By working together as a project is developed and progresses,” Tabor says, “we can proactively identify and study the kinds of ethical questions and challenges that arise and provide solutions in real time.”

Dr. Dan Miller – new applications for advanced sequencing technology

Miller 220x130Dr. Dan Miller is finding new uses for stem cells and for technologies originally developed to sequence the human genome. He employs high-throughput sequencing to identify genes with disease-causing mutations and then uses gene therapy strategies to study and potentially treat human genetic diseases.

He also applies this technology to generate mutations that are similar to those causing inherited disease so he can study the cellular effects of the mutations. Miller is also using induced pluripotent stem cells to model developmental transitions that are often important for genetic disease phenotypes.

Seattle is home to an unprecedented collaboration of high-powered institutions with incredible resources. It's a clinical researchers dream to drive basic science from bench to the bedside." ~Dr. Dan Miller

Miller’s primary investigations of the molecular pathophysiology of Facioscapulohumeral Muscular Dystrophy (FMD) have him collaborating with scientists throughout the world to determine the molecular events that cause this largely inherited, adult-onset disease. Along the way he has also met many local families affected by this common form of muscular dystrophy that initially weakens the skeletal muscles of the face, but often results in wheelchair dependency and can also shorten a patient’s life.

“Knowing these patients and their families gives my research a heightened sense of urgency,” he says. “It’s less academic and more real.”

It’s also more possible.

Several families formed a fundraising guild to support research in Miller’s lab. The results were promising enough to secure funding from the National Institutes of Health to continue the work.

“Seattle is home to an unprecedented collaboration of high-powered institutions with incredible resources,” says Miller. “It’s a clinical researcher’s dream to drive basic science from the bench to the bedside. Geneticists here want to be part of developing a therapy for genetic disease.”