BLG 400 (Genetics)

BLG 600 & 700 (Human Anatomy and Physiology)

BLG 702 (Genomics and its Applications)

BLG 788 (Topics in Biotechnology)

BLG 875 (Developmental Biology)

SCI 181 (Biology of the Living City)

My research program is concerned with understanding the mechanisms and molecules that govern the guidance of cell and axon migrations during development of the nervous system. Neuronal cell bodies migrate from their birthplace to their final destinations and then send out processes that become axons and dendrites. Some axons migrate over extremely long distances to get to their final destinations using cues and receptors on the growth cones at the tips of the migrating axon that are still only partly understood. For instance, humans have individual axons that extend from the spinal cord to the toes where they form synapses with their final targets and vice versa . The model organism that I am using for this research is the microscopic, non-parasitic nematode, Caenorhabditis elegans which has proven to be extremely useful for the identification of axon guidance molecules . This organism has only 302 neurons while the human brain is extremely complex with an estimated 100 billion neurons. Individual neurons can be seen using neuron specific promoters to drive green fluorescent protein. My group conducted a classic visual genetic enhancer screen to find new mutants that enhanced the motor axon outgrowth defects of the DA and DB classes of motor neurons in a strain with a mutation in the UNC-6/Netrin receptor UNC-5. The screen uncovered five mutants and one mutant gene encoded a novel protein called ENU-3 ( En hancer of U nc) expressed throughout the nervous system (Yee et al., 2011). We are currently characterizing this protein further by performing forward and reverse genetic and biochemical experiments to further understand ENU-3's function in the guidance of other neurons. In future my group will identify the other genes mutated in our screen and determine how they function to control axon outgrowth and guidance.

Professor in the Graduate Program in Molecular Science at Ryerson University. http://www.ryerson.ca/graduate/programs/molecular_science/

Adjunct Professor in the Graduate Program in Biology at York University. http://www.biol.yorku.ca/grad/

WormBase profile at: http://www.wormbase.org/db/misc/person?name=WBPerson3027;class=Person

COS profile at: http://myprofile.cos.com/mariekilleen.

Member of Canadian Federation of Biological Societies, Canadian Genetic Society, Canadian Society of Biochemistry and Molecular & Cellular Biology, Genetic Society of America, American Society of Cell Biology and the Society for Developmental Biology.

Peer Reviewed Publications.

Yee, C. S., Sybingco, S. S., Serdetchania, V., Kholkina, G., Bueno de Mesquita, M., Naqvi, Z., Park, S.-H., Lam, K., Killeen, M. T. (2011). ENU-3 is a novel motor axon outgrowth and guidance protein in C. elegans. Dev. Biol. 352: 243–253.

Killeen, MT. (2009) The dual role of the ligand UNC-6/Netrin in both axon guidance and synaptogenesis in C. elegans. Cell Adh Migr.; 3: 268-371.

Killeen, M. T., and Sybingco, S. S. (2008) Netrin, Slit and Wnt receptors allow axons to choose the axis of migration. Scholarly review. Dev. Biol., 323: 143-151.

Killeen, M., Tong, J.F., Krizus, A., Steven, R., Scott, I., Pawson, A., and Culotti, J. (2002) UNC-5 Function Requires Phosphorylation of Cytoplasmic Tyrosine 482, but its UNC-40 Independent Functions also Require a Region Between the ZU-5 and Death Domains. Dev. Biol.; 251: 348-366.

Tong, J., Killeen, M., Steven, R., Binns, K.L., Culotti, J., Pawson, T. (2001) Netrin Stimulates Tyrosine Phosphorylation of the UNC-5 Family of Netrin Receptors and Induces Shp2 Binding to the RCM Cytodomain. J. Biol. Chem.; 276: 40917-40925.

Merz, D., Zheng, H., Killeen, M.T., Krizus, A., Culotti, J.G. (2001) Multiple signaling mechanisms of the unc-6/netrin receptors unc-5 and unc-40/dcc in vivo. Genetics 158: 1071-1080.

Su, M. W., Merz, D. C., Killeen, M. T., Zhou, Y., Zheng, H., Kramer, J., Hedgecock, E. M. and Culotti, J. G. (2001) Regulation of the UNC-5 netrin receptor initiates the first reorientation of migrating distal tip cells in Caenorhabditis elegans. Development 127: 585-594.

Chan, S.S.-Y., Zheng, H., Su, M.-W., Wilk, R., Killeen, M.T., Hedgecock, E.M., and Culotti, J.G. (1996). UNC-40, a C. elegans homolog of DCC (deleted in colorectal cancer), is required in motile cells responding to UNC-6 netrin cues. Cell 87:187-195.

Killeen, M., Coulombe, B., and Greenblatt, J. (1992) Recombinant TBP, transcription factor IIB, and RAP30 are sufficient for promoter recognition by mammalian RNA polymerase II. J. Biol. Chem. 267: 9463 9466.

Killeen, M., and Greenblatt, J.F. (1992) The general transcription factor RAP30 binds to RNA polymerase II and prevents it from binding nonspecifically to DNA. J. F. Mol. Cell Biol. 12:30-37.

Coulombe, B., Killeen, M., Liljelund, P., Honda, B., Xiao, H., Ingles, C. J., and Greenblatt, J. (1992) Identification of three mammalian proteins that bind to the yeast TATA box protein TFIID. Gene Expression 2: 99 110.

Flores, O., Killeen, M., Lu, H., Greenblatt, J., Burton Z., and Reinberg, D. (1991) The small subunit of transcription factor TFIIF specifically recruits RNA polymerase II into preinitiation complexes. Proc. Natl. Acad. Sci. U.S.A. 88: 9999 10003.

Burton, Z. F., Killeen, M., Sopta, M., Ortolan, L. G. and Greenblatt, J. (1988) RAP30/74: a general initiation factor that binds to RNA polymerase II. Mol. Cell. Biol. 8: 1602 1613.

Current graduate students: Zafaryab Naqvi, Callista Yee

Current undergrads: Viktoria Serdetchania, Ganna Kholkina, Tracy Lacraj,
Ari Morgenthau

Past graduate students: Stephanie Sybingco, Matthew Bueno de Mesquita