J. William Harbour

J. William Harbour, M.D., is an ophthalmologist, ocular oncologist and cancer researcher. He currently serves as the vice-chairman for Translational Research and director of ocular oncology at the Bascom Palmer Eye Institute and the associate director for basic research at the Sylvester Comprehensive Cancer Center of the University of Miami Miller School of Medicine. His clinical practice focuses on intraocular tumors, including uveal (ocular) melanoma, retinoblastoma, lymphoma and other neoplasms. His field of research includes the genetics and genomics of cancer, with a focus on prognostic biomarkers, mechanisms of metastasis, and molecular targeted therapies. He has given over 300 invited scientific lectures, and published over 150 peer-reviewed scientific articles and book chapters. Dr. Harbour founded the Ocular Oncology Service at the Washington University School of Medicine in St. Louis, where he was the Paul A. Cibis Distinguished Professor of Ophthalmology & Visual Sciences.^[1][2][3]

Early life and education

J. William Harbour, M.D., is a native of Dallas, Texas. He graduated from Hillcrest High School and earned his undergraduate degree in biochemistry at Texas A&M University where he graduated Summa Cum Laude. Harbour then attended medical school at Johns Hopkins, where he developed a keen interest in interest in cancer biology. He completed medical school in 1990, followed by ophthalmology residency at the Wills Eye Hospital in Philadelphia, clinical fellowship in vitreoretinal diseases and surgery at the Bascom Palmer Eye Institute, and ocular oncology fellowship at the University of California at San Francisco.

Medical career

After his medical training, Harbour accepted a position as assistant professor at Washington University in St. Louis, where he remained for 16 years and rose through the ranks to the title of Paul A. Cibis Distinguished Professor of Ophthalmology, professor of medicine and professor of cell biology and physiology. In 2012, he returned to the University of Miami as professor of ophthalmology, orofessor of biochemistry and molecular biology, vice chair for translational research at the Bascom Palmer Eye Institute, and director of ocular oncology at Bascom Palmer and the Sylvester Comprehensive Cancer Center. In 2015, he was named the associate director for Basic Research at Sylvester and serves as medical director for clinical research at Bascom Palmer. He established the Bascom Palmer ocular oncology fellowship program and serves as the fellowship director.

Research

Harbour developed a keen interest in research during his undergraduate years at Texas A&M, where he studied the function of the copper protein ceruloplasmin in the laboratory of Dr. Edward Harris. During school, he was accepted to the Howard Hughes Medical Institute–National Institutes of Health (HHMI–NIH) Research Scholars Program in Bethesda, MD, where he took 18 months from medical school to carry out research in the National Cancer Institute laboratory of Dr. John Minna. This research resulted in a breakthrough discovery published in the journal Science in 1988, with Harbour as first author. Previously it had been thought that mutations in the retinoblastoma gene, the first tumor suppressor gene to be discovered, would be limited to the rare eye cancer retinoblastoma. However, Harbour and co-authors showed that the gene was commonly mutated in a common form of lung cancer. This discovery added to increasing recognition of the retinoblastoma tumor suppressor pathway as a common target of mutation in the vast majority of human cancers.

When Harbour joined Washington University in 1996, he underwent a three-year postdoctoral research training program in molecular oncology, which resulted in a first author publication in the journal Cell describing how the retinoblastoma protein is regulated by successive phosphorylation events. This discovery was recently corroborated by protein crystallography and other lines of investigation and have helped to explain how cancer cells inactivate the retinoblastoma protein by phosphorylation rather than mutation. In the early 2000s, the focus of Harbour's research turned to uveal melanoma, where he discovered a gene expression profile that predicted with astonishing accuracy which of these cancers would remain localized to the eye and which would metastasize.New York Times,^[4]

Based on this discovery, he developed a highly sophisticated and accurate prognostic test for widespread clinical use. Harbour conducted the largest multicenter prospective validation study of its kind ever conducted in the field of ocular oncology to validate the prognostic accuracy of this test, which is now widely regarded as among the most accurate for any type of cancer. The test has been showcased in a front-page story in the New York Times, in a segment on CBS News Sunday Morning, and other media outlets. This test has been commercialized as DecisionDx-UM, which is available from Caste Biosciences, Inc.

In 2010, Harbour was first author on a landmark paper describing frequent mutations in the tumor suppressor gene BAP1 in uveal melanoma. These mutations were strongly associated with metastasis, thereby opening a new avenue of research into the cause of metastasis in this cancer. In 2013, Harbour was first author on another landmark paper describing frequent mutations in the splicing factor SF3B1 in uveal melanoma. Unlike BAP1, mutations in SF3B1 were associated with better clinical outcomes. In 2016, the Harbour lab reported on a new biomarker in uveal melanoma – PRAME. They showed that expression of the cancer-testis antigen PRAME in uveal melanoma was associated with increased metastatic risk, but it might also indicate tumors that could be responsive to immunotherapy directed against PRAME.

Discoveries

• Discovery that mutations in the retinoblastoma gene are common in small cell lung cancer.
• Discovery of the mechanism by which successive phosphorylation events inactivate the retinoblastoma protein.^[5]
• Discovery of a gene expression profile that predicts metastasis in uveal melanoma. This discovery led to the development of the most widely used clinical test today.^[6][7][8]
• Discovery of driver mutations in the tumor suppressor gene BAP1 in uveal melanoma, which are tightly associated with metastatic death.^[9]
• Discovery of driver mutations in the splicing factor SF3B1 in uveal melanoma, which are associated with good prognosis.^[10]
• Discovery that histone deacetylase inhibitors reverse the biochemical effects of BAP1 mutation and may a role in targeted systemic therapy for uveal melanoma.^[11]
• Discovery of the biomarker PRAME as a risk factor for metastasis in uveal melanoma.^[12]

Clinical accomplishments

Dr. Harbour is fellowship trained in surgical retina and ocular oncology, and he has treated thousands of patients with uveal melanoma, retinoblastoma, ocular metastatic disease, ocular hemangiomas, ocular hamartomas and many other ocular tumors. He has trained over 50 clinical fellows, and receives patients from around the world. He has pioneered new surgical methods regarding fine needle biopsy, laser treatment and brachytherapy of ocular tumors.

Other notable discoveries

Among Dr. Harbour's notable discoveries is a prognostic test, DecisionDx-UM, which accurately determines the metastatic risk related to ocular melanomas. Ocular melanoma is a term commonly used to describe tumors of the uveal tract, including choroidal melanoma. This test was developed in Dr. Harbour's lab at Washington University in St. Louis, MO.^[13]

Awards and recognition

In 2005, Harbour received the prestigious Cogan Award from the Association for Research in Vision and Ophthalmology (ARVO), recognizing the most promising young researcher in vision science worldwide. In 2008, he received the Rosenthal Award from the Macula Society for an "individual under 50 years of age whose work gives high promise of a notable advance in the clinical treatment of disorders of the eye." In 2012, he received the Senior Achievement Award from the American Academy of Ophthalmology. In 2013, he received the Florida Society of Ophthalmology Shaler Richardson, MD Service to Medicine Award for "personal contribution to quality patient care by collaborating and integrating ophthalmology into the medical profession on a national level." In 2014, he received the Paul Henkind Memorial Award from the Macula Society for outstanding retinal research. In 2015, he received the Retina Research Foundation / Kayser Global Award "for Dr. Harbour's breakthroughs in genetic and genomic research."

Other notable awards

• Paul A. Cibis Distinguished Professor, Washington University in St. Louis
• Alcon Research Institute, Basic Sciences Award
• Retina Research Foundation / Kayser Global Award
• Senior Scientific Investigator, Research to Prevent Blindness, Inc.

External links

• Bascom Palmer Eye Institute, University of Miami
• Sylvester Comprehensive Cancer Center, University of Miami
• Johns Hopkins Medicine – Health
• My Uveal Melanoma, Ask the Doctor: Dr. J. William Harbour
• American Academy of Ophthalmology, MD Roundtable: Choroidal Nevus or Melanoma? – By Arun D. Singh, MD, with Bertil E. Damato, MD, PhD, and J. William Harbour, MD
• Research Gate, Driver Mutations in Uveal Melanoma: Associations With Gene Expression Profile and Patient Outcomes
• Eurek Alert, New biomarker identifies uveal melanoma patients at high risk for metastasis
• Biomarker expression may predict metastasis in uveal melanoma
• US National Library of Medicine National Institutes of Health – Genomic, Prognostic, J. William Harbour, MD and Cell-Signaling Advances in Uveal Melanoma,
• The Smart Science Aggregator – Researchers discover new biomarker that puts patients at higher risk for metastasis of uveal melanoma
• Johns Hopkins University – Official site
• Hillcrest High School, Dallas, Official site
• Texas A&M University, College Station, TX – Official site
• Sylvester Researchers Study Size and Gene Expression to Classify Uveal Melanomas | Miller School of Medicine | University of Miami

See also

• Ophthalmology
• Eye cancer
• DecisionDx-UM

References