J. William Harbour, M.D.

Ocular Oncology Website

Click here to visit Dr. Harbour's Faculty Practice Page

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

(314) 362-3315
(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.

CV and Publications:

Click here to view Dr. Harbour's CV

Click here to view Dr. Harbour's Publications