Dr. Jonathan Lee
Professor
Degree:
B.Sc. (UWO), Ph.D. (Toronto)
Contact info:
Roger Guindon Hall, Rm. 4256
Phone: 562-5800 x 8640
Email: jlee@uottawa.ca
Research Interests
The lab is broadly interested in 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 PCR mutagenesis to name a few. There are two ongoing research themes in the lab: a) Remodeling of the actin cytoskeleton b) The role of protein elongation factor eEF1A2 in ovarian and 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 PI4KIIIb. We are studying how these two proteins control actin and filopodial assembly in migrating cells.
Ovarian and Breast Cancer
In 2008, it is expected that over 2,500 Canadian women will be diagnosed with ovarian cancer and 23,000 with breast cancer. There is currently no effective treatment for ovarian cancer: 5-year survival is below 50%, and 10-year survival is almost 0%. We have discovered a new gene involved in ovarian and breast cancer, protein elongation factor eEF1A2. About 1/3 of ovarian and breast tumours express more eEF1A2 than normal tissue. Importantly, eEF1A2 has properties of an oncogene, that is, it increases the growth rate of human cells cultured in the lab. Our work with eEF1A2 has three components: a) Using bioinformatic and proteomic technology, we are trying to understand how eEF1A2 promotes tumorigenesis; b)We are making transgenic mice that express eEF1A2 and analyzing the effect that eEF1A2 has on tumour formation; c) We are designing novel cancer agents that function by inactivating eEF1A2.
Funding
Funding in the lab is provided by operating grants from NSERC, The Cancer Research Society and the Heart and Stroke Foundation.
Selected Publications:
- 1. 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. (Read artlicle)
- I.H. Cukier, Y. Li, & J.M. Lee. 2007. Cyclin B1/Cdk1 binds and phosphorylates Filamin A and regulates its ability to cross-link actin. FEBS Lett. (Read article)
- D.E. Pinke, S. Kallogher, D.A. Huntsman & J.M. Lee. 2008. The prognostic significance of elongation factor eEF1A2 in ovarian cancer. Gynecol Oncol. 108: 561-8. (Read article)
- S. Jeganathan & J.M. Lee. 2007. Binding of elongation factor eEF1A2 to Phosphatidylinositol-4 kinase beta stimulates lipid kinase activity and phosphatidyl-4 phosphate generation. J. Biol. Chem.. 282:372-80. (Read article)
- J.M. Lee, S. Dedhar, R. Kalluri, & E.W. Thompson. 2006. The Epithelial--Mesnechymal transition: New insights in signaling, development and disease. Journal of Cell Biology. 172: 973-981 (Read article)
- A. Amiri, F. Noei, S. Jeganathan, G.Kulkarni & A. Amiri, F. Noei, S. Jeganathan, G.Kulkarni & J.M. Lee. 2006. eEF1A2 activates Akt and stimulates Akt-dependent actin remodeling, invasion and migration. Oncogene. Epub November 20. (print citation: 2007. 26:3027-40).2006 (Read article)
- S. Thornton, N. Anand, D. Purcell, & J.M. Lee. 2003 Not Just for Housekeeping: Protein Initiation and Elongation Fractors in Cell Growth and Tumorigenesis. Journal of Molecular Medicine. 81:536-548. (Read article)
- N. Anand, S. Murthy, M. Wernick, L.A. Porter, I.H. Cukier, C. Collins, J.W. Gray, D. Demetrick, & J.M. Lee. 2002. Protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer. Nature Genetics. 31:301-305 (Read article)