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John David York

Adjunct Professor in the Department of Pharmacology & Cancer Biology
Pharmacology & Cancer Biology
Duke Box 3813, Durham, NC 27710
C203 Lev Sci Res Ctr, Durham, NC

Overview


My laboratory is interested in the biology of cellular communication networks and the mechanisms by which defects in these pathways contribute to the pathophysiology of human disease. We study a widely utilized communication network, the inositol signal transduction pathway. The classic paradigm of inositol signaling
activation is that receptor stimulation leads to the breakdown of an inositol lipid precursor into two second messengers inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol, which regulate calcium release and protein kinase C, respectively. However, in recent years the tremendous complexity of the inositol metabolic
pathway has become evident. Diverse stimuli from growth factors to light activate molecular programs that lead to the production of numerous inositol polyphosphate (IP) messenger molecules. In all,
over 30 lipid and water-soluble IP molecules have been identified in eukaryotic cells, many of which have not yet been assigned a function in cells and hence have been designated as "orphan" IP molecules.

Our research efforts have focused on expanding the understanding of the pathway by seeking to identify the cellular targets and processes influenced by "orphan" IP messengers. We have utilized a multidisciplinary approach, which includes Pharmacology, Biochemistry, Genetics, Biophysics and Cell Molecular Biology, to
characterize the function of over ten gene products that regulate the synthesis and breakdown of these molecules. Our work has helped identify new roles for "orphan" IP messengers in the regulation of
diverse processes including membrane trafficking, cytoskeletal organization, gene expression, and mRNA export. Furthermore, we have found that an additional layer of complexity is achieved through the
compartmentalization of IP pathways to the nucleus. In addition, by determining the X-ray crystal structure of one of the enzymes we have uncovered a novel family of lithium targets with relevance to manic
depressive disease. These discoveries have led us to revise the classic paradigm of inositol signaling to include several new inositol second messengers and have uncovered new areas of research aimed at understanding a fundamental problem in biology - that of how diverse stimuli utilize IP signaling pathways to achieve specific
cellular responses.

Current Appointments & Affiliations


Adjunct Professor in the Department of Pharmacology & Cancer Biology · 2012 - Present Pharmacology & Cancer Biology, Basic Science Departments

Education, Training & Certifications


Washington University in St. Louis · 1993 Ph.D.