Dr. John D. York, Howard Hughes Medical Institute Assistant Investigator, Duke University Medical Center, focuses on the elucidation of communication pathways between cells - a process called signaling - and the mechanisms by which defects in these pathways may lead to diseases such as manic depression and cancer.
Dr. York is perhaps best known for identifying biological roles for "orphan" intracellular signaling molecules known in general as inositol polyphosphates, a discovery which changed how scientists regard inositol signaling and its possible impact on disease and the design of new therapies.
His own previous work illustrates the impact of these little understood molecules. As a graduate student, Dr. York took apart the three dimensional structure of inositol polyphosphate 1-phosphatase, an enzyme that many scientists suspected was the target of lithium. At the center of the enzyme he found and was able to characterize a unique structure he then used as a guide to identifying other enzymes that could serve as additional targets for lithium. This work also may provide the basis for the design of more specific drugs that may not have the negative side effects some patients experience on lithium. He found that lithium inhibits some very specific cellular enzymes. Simultaneously, however, the drug also inhibits other very specific cellular enzymes and inhibition of those enzymes may contribute to unwanted side effects. His more recent work has defined a sequence motif capable of rapidly identifying new lithium targets from emerging genome databases.
This work continues but at his lecture Dr. York also will be speaking about the areas of nuclear inositol signaling and phosphatase regulation of inositol lipid messengers. Understanding the cellular functions of these phosphatases and their lipid signaling molecule substrates will help explain why defects in these phosphatases result in human diseases such as cancer, myotubular myopathy and Lowe syndrome, also known as OCRL (oculo-cerbro-renal) syndrome. His recent work in signaling pathways suggests that these enzymes coordinate multiple cellular functions, an understanding that should open the way for defining and correcting these metabolism errors.