Reed B. Wickner, MD, NIH Distinguished Investigator and chief, Laboratory of Biochemistry and Genetics at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), will be the leadoff speaker for the 2011 Senior Vice Chancellor’s Laureate Lecture Series, a year-long program highlighting some of the top biomedical researchers in their fields.

His lecture, titled “Yeast Prions: Pathology, Biology, and Structure,” will focus on yeast prion research and will take place at noon on Thursday, April 14, in Scaife Hall, Auditorium 6.

For nearly two decades, Wickner has been quietly working on solving the mystery of one of the least well-understood yet deadliest of all disease families—prion infections. As the etiologic agents believed to be responsible for scrapie in sheep and goats, bovine spongiform encephalopathy in cattle (“mad cow” disease), and Creutzfeld-Jakob disease, kuru, and others in humans, prions are infectious misfolded proteins absent of nucleic acid that induce irreversible amyloid formation in brain and neural tissue. There is no known treatment for prion infection; and the disease, once neurodegenerative symptoms develop, is rapidly and uniformly fatal.

In 1994, Wickner and colleagues discovered that the budding yeast Saccharomyces cerevisiae could have prion infections.  Based on a genetic approach that he developed, he showed that two long-known non-chromosomal genetic elements, [URE3] and [PSI], were altered forms of their normal counterpart proteins, Ure2p and Sup35p, that had acquired the ability to transmute the normal form into the abnormal prion form.  The genetic approach he developed was three, now oft-cited genetic criteria for identifying: (1) reversible curability: unlike viruses or plasmids, prions can arise de novo or reappear spontaneously in a previously “cured “ strain, (2) overproduction risk: excess production of the normal protein increases the risk of prion formation, and (3) phenotypic similarity to mutant forms: the phenotype of an organism infected by a prion is the same as the phenotype of a mutant in the gene encoding the protein.  Wickner characterized the prion domains of these proteins, showing that they form in-register parallel beta-sheet infectious amyloids, thus explaining how a protein can be a gene.  His studies of the biological properties of these prions have shown that yeast prions are diseases of yeast.

Current and future research directions for the Wickner lab include further studies of the structure of yeast prion amyloids, development of laboratory methods to search for new prions, and genetic screens to find proteins that affect prion generation and propagation.

Wickner earned his undergraduate degree in mathematics from Cornell University and his medical degree from Georgetown University School of Medicine. He completed a medical internship at North Carolina Memorial Hospital. In 1967, he joined NIDDK as a pharmacology research associate and, except for a three-year stint as a Helen Hay Whitney Fellow in the Department of Developmental Biology and Cancer at Albert Einstein College of Medicine, has spent his entire career there. He has risen in rank at NIDDK to his current position as chief of the Laboratory of Biochemistry and Genetics (a post he has held for the last 15 years) and is an NIH Distinguished Investigator.

Wickner’s many honors include the Norman P. Salzman Mentor Award in Virology and the U.S. Public Health Service Meritorious Service Medal, Outstanding Service Medal, and Commendation Medal. He is a member of the National Academy of Sciences, American Academy of Arts and Sciences, American Academy of Microbiology, and a fellow of the American Association for the Advancement of Science.