Biography
Research Interests
Looking for Graduate and Honours Students
The lab is broadly interested in breast cancer and the molecular biology of cell motility. To study these processes we use state-of-the-art technologies: bioinformatics, proteomics, high-resolution fluorescence microscopy, live cell microscopy and protein biochemistry to name a few. There are two ongoing research themes in the lab:
- Remodeling of the actin cytoskeleton during cell migration
- The role of the lipid kinase PI4KB in breast cancer.
Filopodia and the actin cytoskeleton
Filopodia are finger-like projections from the cell membrane thata are composed primarily of actin fibers bundled together. Filopodia have important roles in initiating cell migration and in attaching cells to their growth substrate. My lab is interested in understanding, at the molecular level, how filopodia form and how they regulate cell migration. We are particularly interested in two proteins: Filamin A and PI4KB. We are studying how these two proteins control actin and filopodial assembly in migrating and dividing cells.
Breast Cancer
In 2014, it is expected that approximately 23,000 Canadian women will be diagnosed with breast cancer. We have discovered a new gene involved in breast cancer, the lipid kinase PI4KB. About 1/4 of human breast tumours express more PI4KB than normal tissue. Importantly, PI4KB has properties of an oncogene, that is, it activates several oncogenic signaling pathways and disrupts cell migration and morphology. Our work with PI4KB has four components:
- Using bioinformatic analysis of gene expression in human breast tumours to identify signaling pathways activated by PI4KB.
- We are making transgenic mice that express PI4KB and analyzing the effect that PI4KB has on tumour formation and metastases.
- We are determining the effect that PI4KB has on endosome recycling based on the idea that the endocytic compartment is a signaling nexus for tumour promotion.
- We are designing novel cancer agents that function by inactivating PI4KB.
Funding
Funding in the lab is provided by operating grants from the Canadian Breast Cancer Research Foundation.
Selected Publications
- S. Szeto, E.C. Williams, A.D. Rudner & J.M. Lee. 2014. Mitotic phosphoryaltion of FLNa by cyclin B1/cdk1 regualtes cell shape, motility and clustering beahvior. In press. Exp. Cell Res.
- A.A. Morrow, M.A. Alipour, D. Bridges, Z. Yao, & J.M. Lee. 2014. The lipid kinase PI4KIIIb activates Akt and is highly expressed in breast tumours. 2014. Mol. Cancer Res. 10:1492.
- J.M. Lee. 2013. The actin cytoskeleton and the Regulation of Cell Migration. in I.R. Nabi (ed). Building Blocks of the Cell: Cell Structure and Function. Morgan & Claypool Life Sciences.
- S.F. Thurston, W.A. Kulacz, S. Shaikh, J.M. Lee, & J.W. Copeland. 2012. Formin-induced microtubule acetylation associates with the ability to regulate actin dynamics. PLOS One. 7(10): e48041
- D.E. Pinke & J.M. Lee. 2011. The lipid kinase PI4KIIIβ and the eEF1A2 oncogene co-operate to disrupt three-dimensional in vitro acinar morphogenesis. Exp. Cell Res. 317: 2503-11.
- J.S. Jeganathan, A. Morrow, A. Amiri, & J.M. Lee. 2008.Elongation factor eEF1A2 cooperates with phosphatidylinositol-4 kinaseIIIb to stimulate PI(4,5)P2 generation and filopodia production. Mol. Cell. Biol. 14:4549-61.