Faculty > Harbour

J. William Harbour, M.D.

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Ocular Oncology Website
Paul A. Cibis Distinguished Professor of Ophthalmology
Professor of Cell Biology & Physiology
Professor of Medicine/Molecular Oncology

(314) 747-1738
(fax) 747-5073

B.S. Biochemistry, Texas A&M Univeristy (1985); Fellow, Molecular Genetics of Retinoblastoma, Howard Hughes NIH Research Scholars Program (1987-1988); M.D. Johns Hopkins University, Baltimore, MD (1990); Resident in Ophthalmology, Wills Eye Hospital, Philadelphia, PA (1991-1994); Fellow in Vitreoretinal Surgery, Bascom Palmer Eye Institute, Miami, FL (1994-1995); Fellow in Ocular Oncology, University of California, San Francisco, CA (1995-96)

Research Area:

Ocular Oncology

Research Interests:

  1. Role of the retinoblastoma protein in retinal development and tumorigenesis
    Mutation of the retinoblastoma protein (Rb) leads to the development of the childhood eye cancer called retinoblastoma. Paradoxically, loss of Rb can also lead to retinal degeneration. Current evidence suggests that Rb functions at a nodal point that regulates cell cycle, differentiation and apoptosis. A better understanding of the role of Rb in these pathways may lead to the development of rational therapeutic interventions not only for retinoblastoma, but also for degenerative retinal diseases.
  2. Molecular genetics of uveal melanoma
    Uveal melanoma is extremely resistant to radiation and chemotherapy, and the molecular basis of this resistance is not known. Uveal melanoma has also been recalcitrant to traditional genetic investigation; it is rarely transmitted in a hereditary fashion, ruling out positional cloning and linkage analysis as a technique for identifying causative gene mutations, and it rarely contains mutations in common tumor suppressors such as Rb, p53 and p16. We have adopted a functional approach to investigate the molecular pathogenesis of uveal melanoma by studying the status of tumor suppressor checkpoints. Using this approach, we recently showed that p53 is functionally inactivated in uveal melanoma by overexpression of its inhibitor, HDM2. Further studies using new microarray technology will allow us to further dissect the genetic changes in uveal melanoma, eventually leading to the rational design of novel therapies.
  3. Molecular therapy for eye cancer
    Uveal melanoma and retinblastoma are the most common eye cancers in adults and children, respectively. Key mutational events in the pathogenesis of these cancers have recently been identified, making it possible to design targeted molecular therapy using novel therapeutic agents. Eye cancer provides an excellent model for testing novel cancer therapies in vivo due to the availability of good animal models. We are currently developing molecules that reactivate the Rb and p53 checkpoints in tumor cells, leading to growth arrest and apoptosis.

Selected Publications:

  1. Harbour JW, Luo RX, Dei Santi A, Postigo AA, Dean DC. Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell 1999; 98:859-969
  2. Harbour JW, Dean DC. Rb function in cell-cycle regulation and apoptosis. Nature Cell Biol 2000; 2:65-67.
  3. Harbour JW, Dean DC. The Rb/E2F Pathway: Emerging paradigms and expanding roles. Genes Dev 2000; 14:2393-2409.
  4. Harbour JW, Dean DC. Chromatin remodeling and Rb activity. Curr Opin Cell Biol 2000; 12: 685-689.
  5. Zhang HS, Gavin M, Dahiya A, Postigo AA, Ma D, Luo RX, Harbour JW, Dean DC. Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF. Cell 2000; 101:79-89.
  6. Brantley MA, Harbour JW. Inactivation of retinoblastoma protein in uveal melanoma by phosphorylation of sites in the COOH-terminal region. Cancer Res 2000; 60: 4320-4323.
  7. Brantley MA, Harbour JW. Deregulation of the Rb and p53 pathways in uveal melanoma. Am J Pathol 2000; 157:1795-1801.
  8. MA, Harbour JW. The molecular biology of retinoblastoma. Ocul Immunol Inflamm 2001;9:1-8.
  9. Harbour JW. Molecular mechanisms of low penetrance retinoblastoma. Arch Ophthalmol 2001; 119:1699-1704.
  10. Brantley MA, Worley L, Harbour JW. Alterations in expression of Rb and p53 in uveal melanomas following plaque radiotherapy. Am J Ophthalmol 2002; 133:242-248.
  11. Worley L, Ma D, Cohen M, Harbour JW. Transducible peptide therapy for uveal melanoma and retinoblastoma. Arch Ophthalmol (November, 2002).


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