Harbour Lab

Meet the PI

Lab Members

Mahsa Sorouri

Mahsa Sorouri, Ph.D. (Lab Manager)

Jie Han, M.S.

Jie Han, M.S. (Research Scientist)

Mechanisms of Tumor Progression in Eye Cancer

Dr. J. William Harbour’s research focuses on the use of genetic and genomic technology, cell biology, and genetically modified experimental animal models to elucidate mechanisms of tumor progression and metastasis in major forms of lethal eye cancers, including uveal melanoma and retinoblastoma.

Uveal Melanoma

Over the past two decades, the Harbour Laboratory has made great strides in understanding uveal melanoma, the most common primary cancer of the eye. The lab found that uveal melanomas can be divided into two basic forms, based on gene expression profile, mutation status, and chromosomal alterations. Class 1 uveal melanomas have low metastatic risk, whereas class 2 uveal melanomas have high metastatic risk. Based on this discovery, the lab developed a clinical prognostic test based on a 15-gene signature that has been prospectively validated in multiple studies and is currently the standard of care for precision medicine in this cancer type. Further, the lab discovered that mutational inactivation of the tumor suppressor BAP1 accounts for the class 2 uveal melanoma tumor type, as well as a novel BAP1 familial cancer syndrome, which is transmitted in an autosomal dominant fashion and can include uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma, meningioma, and other cancer types.

Recently, the lab discovered that the cancer-testis antigen PRAME can be aberrantly expressed in uveal melanoma, representing an independent prognostic factor in both class 1 and class 2 uveal melanomas. Further work in the lab has disclosed a functional role for PRAME in chromosomal instability, aneuploidy, and tumor progression.

Retinoblastoma

The Harbour Laboratory has established tumor samples and cell lines from a large number of primary human retinoblastoma samples and has undertaken an unprecedented scope and depth of genomic analysis that has disclosed a new understanding of retinoblastoma progression. The lab discovered ESRRG as one of the key drivers of retinoblastoma progression. This estrogen-related orphan receptor plays an essential role in retinal development, hypoxic adaptation, and retinoblastoma progression.

Research Directions

Major research directions in the lab include:

  • Elucidate how BAP1 mutations and aberrant PRAME expression drive uveal melanoma progression, with a focus on how these genomic aberrations alter the tumor immune microenvironment.
  • Elucidate how aberrant ESRRG expression and other recurrent genomic aberrations in retinoblastoma drive tumor progression, metastasis, and poor prognosis, with a focus on altered oxygen metabolism.
  • Determine how to therapeutically disrupt key drivers of tumor progression in uveal melanoma and retinoblastoma.

All Publications