Research

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The Lees Lab investigates genes that influence cancer development and progression, with a particular focus on regulators that control stem cell function and/or the decision to proliferate versus differentiate. Many of these genes are epigenetic or cell cycle regulators that influence a wide variety of tumor types. The lab investigates the molecular mechanisms by which these regulators act, their roles in normal development, and how tumor-specific changes in their expression or activity influence tumor development, maintenance, and metastasis using genetically engineered mouse and zebrafish models.

 

Epigenetics

It is well established that deregulation of one or more epigenetic regulators is critical in tumor development or progression. The Lees Lab is currently studying two epigenetic regulators, PRMT5 and BMI1, linked to cancer development and progression, but have important implications on stem cell function. 

PRMT5

Many cancers are addicted to the symetric dimethyltransferase PRMT5.  PRMT5 deficiency or inhibition promotes the inclusion of detained introns within genes associated with cell proliferation. >>more

Bmi1

The Lees lab is using a combination of cell-based approaches and sophisticated mouse models to understand BMI1’s contribution to tumorigenesis. >>more

 

Cell Cycle

Rb1/E2F

pRB is inactivated in the vast majority of human tumors through mutation of either the Rb gene or its upstream regulators.  Current projects are focused on the consequences of Rb mutation on epithelial tumors and non-canonical role of E2F4 in controlling multiciliogenesis>>more

CDK10/Cyclin M

The cdk10/cycM complex was originally implicated in regulation of mitosis, but has subsequently been shown to regulate the formation of primary cilia. Current projects are focused on elucidating the mechanisms that couple EMT to primary cilia formation and identifying the signaling pathways required for cilia-dependent tumor formation. >>more

 

Uveal Melanoma

Uveal melanoma (UM) is the most common tumor of the adult eye.  The Lees Lab is using zebrafish models and genetically engineered human cell lines to establish the molecular mechanisms the promote tumor development and progression and to identify vulnerabilities that could serve as potential targets of therapy. >>more