Cell Polarity

The PAR Cell Polarity Complex:

We have discovered that the PARD3/PARD6/APKC polarity protein complex is a downstream effector of the receptor tyrosine kinase HER2/ERBB2 during transformation of polarized 3D breast epithelial structures. In addition, we have demonstrated that loss of PARD3 cooperates with HER2 to promote metastasis without inducing EMT but, by modulating E-Cadherin junction maturation and decreasing cohesion between HER2 expressing tumor cells. Moving forward, we are investigating how other oncogenes interact with cell polarity proteins and we are also collaborating with bioengineers to investigate the molecular mechanisms that regulate cell-cell cohesion and its implications for metastatic behavior transformed epithelial cells.

Scribble, Lethal Giant Larvae Cell Polarity Proteins:

We have demonstrated SCRIB functions as a tumor suppressor in mammals both dues loss of expression and due the mislocalization from the cell membrane. The latter identifies an unexpected biology where the misclocalized results in a gain-of-function phenotype and not simply as another inactivation mechanism. Moving forward, we use a combination of inducible RNAi mouse model, 3D cell culture and proteomics to understand how SCRIB and LGL proteins regulate the cell biology of normal and cancer cells.