Gregory A. Petsko BA, DPhil, PhD

For over 30 years Dr. Gregory Petsko and his colleague, Prof. Dagmar Ringe, have used protein crystallography, molecular biology, and genetics to probe the relationship between protein structure and function. Their research has been concerned with the three-dimensional structures and dynamics of proteins and their biochemical functions, with a particular focus on the structural basis for efficient enzymic catalysis; direct visualization of proteins in action by timeresolved protein crystallography; the evolution of new enzyme activities; and the biology of the quiescent state in eukaryotic cells.
During the past 10 years, Drs. Petsko and Ringe have pursued groundbreaking research not only on how proteins work, but how they are related to the causes of neurodegenerative diseases. They use the techniques of genetics, structural biology, and structure-guided drug discovery to identify, validate, and exploit novel targets for the treatment of age-related neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Lou Gehrig’s diseases. During the past 10 years, Drs. Petsko and Ringe have pursued groundbreaking research not only on how proteins work, but how they are related to the causes of neurodegenerative diseases.
Alzheimer’s disease starts when a protein that should be folded up properly for normal brain functioning instead misfolds and then aggregates. Interestingly, diseases that affect other parts of the brain also show similar aggregates of misfolded proteins. This suggests that a therapeutic approach developed for Alzheimer’s might also be used to treat many neurological diseases. With this in mind, they have been collaborating with Dr. Scott Small of Columbia University on the development of drugs that will route the Alzheimer’s protein away from the subcellular compartments where misprocessing and aggregation begin. Two of their compounds have shown good results in neurons in cell culture, and are now being tested in mouse models of Alzheimer’s disease.