The ASHG's prestigious Allan Award recognizes substantial and far-reaching contributions to human genetics carried out over a sustained period of scientific inquiry and productivity. According to the ASHG, Kunkel's work is unique in that it covers the entire spectrum of genetics-based research – from identifying genes, to understanding how mutations of these genes cause disease, to finding new diagnostic techniques and new therapies and figuring out how to make them work.
Kunkel was the first to discover, in 1986, the gene that causes Duchenne muscular dystrophy, the most common form of muscular dystrophy. In 1987, he was the first to pinpoint the gene's importance in producing the critically needed muscle protein, dystrophin. In the 1990s, Kunkel demonstrated that injection of either blood stem cells or muscle stem cells can partially restore dystrophin in affected skeletal muscles, a finding that may lead to treatments for many types of muscle disease. More recently, Kunkel has defined the molecular and genetic characteristics of several dystrophin-associated proteins whose disruption also leads to muscular dystrophy.
Today, Kunkel continues to explore the role of these proteins and the more than 40 genes that have now been linked with various muscular dystrophies. His lab is using microarray (gene chip) technology to systematically examine the activity of multiple genes at once, seeking to find patterns common to all muscular dystrophies and those distinct to particular forms of the disease. These patterns will provide insight on how gene mutations affecting dystrophin and its associated proteins lead to muscle weakening and degeneration, while also shedding light on the biology of normal muscle development. This information can then be used to design rational therapies.
Using animal models, Kunkel is testing strategies for cell-based therapy – using muscle stem cells that graft themselves into diseased muscles and deliver normal dystrophin genes.
"We all have the natural capacity to regenerate muscles," Kunkel says. "Why not make use of that regenerative capacity and use it to deliver missing genes?"
Using this approach, his lab has gotten 5 percent of mouse muscles to begin making dystrophin, Kunkel expects this to increase to 20 percent. Once the technique is fully refined, the next step would be clinical trials in humans.
Another major area of research in Kunkel's lab involves genes that influence lifespan. Kunkel's work led to the identification of a single gene on chromosome 4 that gives people an exceptionally long life expectancy. The gene was found by studying centenarians (people aged 98 or older) and encodes microsomal transfer protein, or MTP, a protein involved in the metabolism of fats. Kunkel is now expanding on this work to find additional longevity genes.
"With new technology, we can now analyze 10,000 genes at once, compare patterns from individual to individual, and look for genetic variations that many centenarians share," he says.
As director of the newly formed Children's Hospital Boston Genomics Program, Kunkel also is overseeing research targeting a series of genetically complex conditions, including autism, diabetes, congenital heart disease, and obesity.
A member of the National Academy of Sciences, Kunkel is a Howard Hughes Medical Institute investigator at Children's and Professor of Pediatrics and Genetics at Harvard Medical School.
Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults for over 100 years. More than 500 scientists, including eight members of the National Academy of Sciences, nine members of the Institute of Medicine and 10 members of the Howard Hughes Medical Institute comprise Children's research community. Founded in 1869 as a 20-bed hospital for children, Children's Hospital Boston today is a 300-bed comprehensive center for pediatric and adolescent health care. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information visit: www.childrenshospital.org.