John David York
Cancer Biology Professor of Pharmacology and Cancer Biology

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

Contact Information

  • C203 Lev Sci Res Ctr, Durham, NC 27708
  • Duke Box 3813, Durham, NC 27710

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