William S. Sly, M.D., professor of biochemistry and molecular biology, is the recipient of the Association of American Medical Colleges' 2011 Award for Distinguished Research in the Biomedical Sciences. Given to one recipient a year, the award recognizes outstanding clinical or laboratory research by a medical school faculty member related to health and disease that has contributed to the substance of medicine.
|William Sly, M.D.|
"I'm very grateful that I was nominated by Dr. Philip Alderson and thrilled that his nominee was selected," Sly said. "To be added to the list of very distinguished prior awardees is humbling. I'm honored to accept an award which brings such distinction to Saint Louis University."
The award will be presented at the association's annual meeting in Denver on Saturday, Nov. 5. The association is awarding national recognitions to eight other individuals and one teaching hospital for outstanding contributions to academic medicine.
Over the course of nearly five decades, Sly has worked to solve some of genetics' most daunting mysteries. For thousands, this has meant new treatments for once crippling or fatal diseases. And for one wrongly convicted woman, it meant her freedom.
While watching an episode of television's Unsolved Mysteries involving a woman charged with poisoning her son, Sly noted that the type of urine test used to convict her could not rule out an inherited metabolic disorder with similar symptoms to poisoning. On a hunch, Sly and his colleague independently conducted more tests, and the results pointed conclusively to a genetic disease. Sly presented this new evidence to the prosecution and, largely thanks to the analysis, the charges were dismissed.
Currently the inaugural holder of the James B. & Joan C. Peter Endowed Chair, with a joint appointment as professor of pediatrics, Sly continues the research that has earned him international recognition for his work on lysosomal storage diseases. Before arriving at Saint Louis University, Sly served for two decades as director of the division of medical genetics and professor at Washington University School of Medicine.
In 1973, Sly described the first case of mucopolysaccharidosis VII, a rare genetic condition that now bears his name. Sly syndrome can cause bone defects, mental retardation, and premature death. By studying the molecular basis of this lysosomal storage disorder, Sly made seminal observations that constitute what David Valle, M.D., Henry J. Knott professor and director, McKusick-Nathans Institute of Genetic Medicine has called "some of the most rigorous and thorough work done to date on the treatment of genetic disease."
Cornerstone of Cell Biology
Continuing work at the cellular level, Sly made seminal discoveries on the trafficking of cellular proteins to the lysosome, including the role of mannose 6-phosphate in targeting proteins to the lysosome. These findings are "a cornerstone of cell biology," says Valle, and contributed to Sly's election to the National Academy of Sciences in 1989.
Subsequent research led by Sly stimulated the growth of enzyme replacement therapy that "is revolutionizing the way we manage patients with lysosomal storage diseases," says Valle. Sly and his team discovered a method to transport the enzyme missing in those with Sly syndrome directly to the brain, which previously had been blocked by the blood-brain barrier. This finding holds promise for transporting other medications directly to the central nervous system to treat many other maladies, such as Alzheimer's disease.
Sly's other discoveries in the field of inherited disorders include publication of the first data linking mutations in one type of carbonic anhydrase (CA) to an eye disease causing blindness. He also established the importance of another CA variant to a number of biological processes. Further, Sly led a team that demonstrated the major cause of hemochromatosis and created a screening test for the disorder, making diagnosis possible before symptoms appear. Work by his group has changed how scientists understand the way the body absorbs and distributes iron.
Taken together, Sly's work is "an amazing body of biomedical research devoted to understanding human genetic disease," says Valle. Patients suffering from lysosomal storage diseases in particular can take heart knowing Sly is on the case.
Sly received his undergraduate and medical degrees from Saint Louis University.
He is a member of the National Academy of Sciences and recipient of many awards and recognitions including the 1991 Passano Award (co-recipient); 1999 Coriell Medal; Peter H. Raven Lifetime Achievement Award from the Academy of Science of Saint Louis; Marcel Simon Prize from the Hemochromatosis Society and the World Congress of Iron Metabolism; Distinguished Scientist Award from the Clinical Ligand Assay Society; and 2010 Life for MPS award from the International MPS Network.He is the author of more than 360 peer-reviewed journal articles and coauthor of The Molecular and Metabolic Bases of Inherited Disease.