Harbour Lab / Projects

Role of the Rb pathway in regulation of cell cycle, apoptosis, and differentiation.

Rb is a phosphoprotein that is active when hypo-phosphorylated and inactive when hyperphosphorylated. Rb is progressively phosphorylated and manifests a series of intermediate activities as it is progressively phosphorylated in G1 and S phases. These intermediate activities may help to explain the roles of Rb in regulating cell division, apoptosis, and differentiation. A major regulator of Rb phosphorylation is the tumor suppressor p16Ink4a. We are using cell systems and animal models to study how Rb and p16Ink4a function in concert to regulate differentiation and suppress tumorigenesis in a melanocyte model system.

Cancer stem cells in melanoma.

Malignant progression from normal melanocyte to low-grade melanoma to high-grade melanoma is accompanied by changes in global gene expression consistent with loss of melanocyte differentiation and reversion to a more stem-like phenotype. We are investigating the molecular mechanisms of this reversion and its relationship to melanoma progression by identifying, isolating, and examining populations of cancer stem cells from primary ocular melanomas.

Molecular prognostic testing for cancer.

Gene expression profiling of ocular melanomas can identify patients at high risk for metastasis. Because most intraocular melanomas do not require removal of the eye, we have established the feasibility of performing this analysis on fine needle aspiration biopsies. Transcriptomic profiles from biopsy samples clustered into the same two classes as our whole tumor samples with the same discriminating genes. Further, no loss of predictive accuracy was identified among samples sent from a distant collaborator. We are currently applying this method to specimens obtained locally and from distant geographic locations to stratify uveal melanoma patients based on metastatic risk as part of an ongoing prospective study.