Doctors have learned a great deal about sickle cell disease in the past century. We now know what causes the disorder, and we have some treatments that can give its sufferers longer and more comfortable lives.
But Yuet Wai Kan (Res ’63), the Louis K. Diamond Professor of Hematology at the University of California, San Francisco, wants to do more than just treat the disease.
“Our aim now is to try to cure sickle cell disease,” he says. “There are some drugs and treatments now that are very helpful, but our aim is to try to cure it, so you don’t need to take any more medicine.”
Sickle cell disease is a genetic condition in which the body produces abnormally shaped red blood cells. Whereas normal red blood cells look like a donut without a hole, sickle cells resemble a crescent roll. Because of their shape, sickle cells can get trapped in the body’s circuitry and cause blockages. These cells also die much more quickly than normal blood cells, so the body is always struggling to keep up with production.
Sickle cell disease affects about 100,000 Americans and millions worldwide, primarily in sub-Saharan Africa, the Mediterranean, the Middle East, and Asia. Sickle cell disease and a closely related blood disorder called thalassemia account for the most common genetic diseases on Earth.
To unravel these life-threatening diseases, Kan is spearheading a five-year, $6.7 million study supported by the National Institute of Diabetes and Digestive and Kidney Diseases.
Today, the only cure available is a bone marrow transplant, which is both costly and difficult to come by—siblings make the best donor matches, but the parents of these patients tend to have fewer children for fear of passing on the troublesome genes again. Additionally, because this procedure involves introducing DNA from another person, it carries the risk of a serious complication known as graft-versus-host disease. (Another approach using a virus to introduce a normal globin gene into the patient’s genome is being tested.)
Kan’s group is developing a work-around to the immunological complication of graft-versus-host disease: using the patient’s own blood cells instead. From these, they will render pluripotent stem cells (they aren’t from an embryo, yet they can form all adult cell types). The team will then “reprogram” these blood stem cells using a method that seamlessly corrects the mutations. Because no foreign DNA is used, no immune rejection is expected, he says.
The result: normal blood-cell factories. That’s the hope.
Kan has dedicated his career to decoding these genetic disorders. After completing medical school in Hong Kong, he came to the United States and completed a residency at UPMC where he studied under the late Jack Myers.
“[Myers] was a renowned clinician, diagnostician, and teacher. He was the reason why I chose the University of Pittsburgh,” Kan says.
Kan’s trajectory has also included stints at MIT and Harvard as well as 27 years as a Howard Hughes Medical Institute Investigator. He is a fellow of the Royal Society, London; a member of the National Academy of Sciences, the American Philosophical Society, and the Academia Sinica; and a foreign member of the Chinese Academy of Sciences. He won the Lasker-DeBakey Award for Clinical Medical Research in 1991. In the last 50 years, he has become widely recognized for opening up the fields of genetics and hematology.
For instance, Kan was the first to prove that a single mutation in our DNA can lead to a disease, and the first to use DNA to diagnose a human disease. He discovered a phenomenon called DNA polymorphisms—the singlenucleotide sequence differences between the DNA of individuals. These differences are now widely used for gene discovery and determination of disease susceptibility.
This fall, Kan will receive Pitt’s William S. McEllroy Distinguished Resident Award, an honor bestowed upon outstanding physicians who undertook residency training here.
When asked about all the things he’s accomplished during his career, Kan deflects to the future, to the prospect of a cure.
“We can do these kinds of things in a lab routinely, but the question is how you translate the technique to patients. There’s still a lot of work to be done.”
Photo by Cindy Chew
Better Care Delivery for Vets
BY LORI FERGUSON
After a serving in a number of senior posts for the University of Pittsburgh and UPMC (most recently as interim chair of anesthesiology), Marshall Webster (General and Thoracic Surgery Resident ’70), a Distinguished Service Professor of Surgery and senior vice president of UPMC, is preparing to take on an ambitious new assignment. As a member of the 15-person Commission on Care established by Congress, he’ll examine how best to deliver health care to the nation’s veterans.
Webster is no stranger to the Veterans Health Administration. He served two years of active duty in the U.S. Navy and has also had an ongoing professional relationship with the VA Pittsburgh Healthcare System since 1973. “I initially worked part-time as a surgeon at the VA while also serving as a faculty member at Pitt and a surgeon at UPMC Presbyterian,” he says. Webster is also a former member of a committee that oversees collaborations between UPMC and the VA.
The relationship between the academic medical center and the VA is strong and stretches back decades, Webster explains. UPMC uses the VA Pittsburgh Healthcare System hospital in Oakland as a site for graduate medical education, many Pitt faculty members are on staff there, and many full-time VA physicians have School of Medicine faculty appointments. In the past year or so, there has also been an uptick in the number of veterans receiving treatment at UPMC Presbyterian when the wait time for appointments at the VA exceeds authorized limits. “We’re assisting the VA with patients in a variety of different specialties,” Webster says. “Orthopaedics and women’s health are two large areas in which demand is currently outstripping resources.”
Webster is honored to have received his new appointment. “I always enjoy a challenge,” he says. “And,” he concludes with delight, “I’ve got two granddaughters living inside the Beltway, so I’ll never miss a chance to visit D.C.”