Email: tvanraay@uoguelph.ca
Office: SCIE 3460
Ext: 52864
Lab: SCIE 3405-06
Ext: 56496
Profile | Education | Research | Publications | Links |
Profile
My interest in biological research started as an undergraduate summer research technician at the University of Windsor with Dr. Paul Hebert and then as a senior research project in the laboratory of Dr. Teri Crease. I followed Dr. Crease to the University of Guelph to complete my MSc. after which, I worked for several years in biotech as a Research Scientist at Genzyme and then Genetics Institute, outside of Boston, MA. It was during this time that I discovered the wonders of developmental neurobiology and decided to pursue my Ph.D. in the Neuroscience program at the University of Utah. Working in the laboratory of Dr. Monica Vetter, I studied the role of Wnt signaling during Xenopus retinal development. Following my Ph.D., I took up a collaborative postdoctoral position with Drs. Robert Coffey and Lilianna Solnica-krezel at Vanderbilt University in Nashville, TN. Here I pursued the role of the Wnt antagonist gene, naked, in the early development of the zebrafish embryo. While I continue to study the role of Naked during zebrafish development, I am focusing my attention at the molecular and cellular level to determine exactly how Naked can turn off Wnt signaling.
Education
B.Sc.- University of Windsor
M.Sc.- University of Guelph
Ph.D.- University of Utah
Postdoctoral Fellow- Vanderbilt University
Research
Many of the signaling pathways that are involved in development are also involved in the onset and progression of disease. As an example, the Wnt signaling pathway is required for during many stages of development and in the homeostasis of stem cells in the adult. Perturbation of this pathway in stem cells in the adult often leads to cancer. It is now known that about 80% of colorectal cancers are caused by mutations in the Wnt signaling pathway. As this pathway is important for both proper development and disease, I am curious to know how this pathway can turn it self on and off so many times during development and why it fails to turn off in disease.
To address these questions, I use zebrafish (Danio rerio) as my model system. Zebrafish have quickly become a favourite vertebrate model for both genetics and development. A single female can lay upwards of several hundred eggs and the rapidly developing embryo is transparent allowing for easy observation of internal structures. Further, overexpression or knockdown of genes have become routine and numerous transgenic lines with GFP reporters are becoming available.
I have cloned the Wnt antagonists, naked1 (nkd1) and naked2 (nkd2), in zebrafish and found that they are both necessary and sufficient to antagonize Wnt signaling. Further, I found that Nkd1, but not Nkd2, acts as a negative feedback regulator of Wnt signaling. Currently, I am using biochemical methods that I have tailored to zebrafish to explore the relationship between Nkd1 and other components of the Wnt pathway. I wish to determine where in the signaling cascade Nkd is acting and to determine exactly how and when the Nkd protein acts in vivo. This research will shed light on how signaling cascades self-regulate themselves, and potentially how this regulation is perturbed in disease.
Selected Publications
Van Raay, T.J., Coffey, R.J., Solnica-Krezel, L. (2007) Zebrafish Naked1 and Naked2 antagonize both canonical and non-canonical Wnt signaling. Dev. Biol. 309: 151-168.
Van Raay, T.J.*, Moore, K.B.*, Iordanova, I., Steele, M., Jamrich, M., Harris, W.H. and Vetter, M.L. (2005) Frizzled 5 signaling governs the neural potential of progenitors in the developing Xenopus retina. Neuron 46: 23-36 (*co-first authors as listed).
Winn RA, Marek L, Han SY, Rodriguez K, Rodriguez N, Hammond M, Van Scoyk M, Acosta H, Mirus J, Barry N, Bren-Mattison Y, Van Raay TJ, Nemenoff RA, Heasley LE. (2005) Restoration of Wnt-7a expression reverses non-small cell lung cancer cell transformation through frizzled-9 mediated growth inhibition and promotion of cellular differentiation. J. Biol. Chem. 280: 19625-19634.
Van Raay, T.J. and Vetter, M.L. (2004) Wnt/Frizzled Signaling During Vertebrate Retinal Development. Dev. Neurosci.26: 352-358.
Van Raay T.J., Wang, Y.K., Stark, M.R., Rasmussen, J.T., Francke, U., Vetter, M.L. and Rao, M.S. (2001) Frizzled 9 is expressed in neural precursor cells in the developing neural tube. Dev. Genes Evol.211:453-457.
Wang, Q., Curran, M.E., Splawski, I., Burn, T.C., Millholland, J.M., VanRaay, T.J., Shen, J., Timothy, K.W., Vincent, G.M., de Jager, T., Schwartz, P.J., Towbin, J.A., Moss, A.J., Atkinson, D.L., Landes, G.M., Connors, T.D. and Keating M.T. (1996) Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nature Genet. 12: 17-23.
Burn T.C., Connors T.D., Dackowski W.R., Petry L.R., Van Raay T.J., Millholland J.M., Venet M., Miller G., Hakim R.M., Landes G.M., et al. (1995) Analysis of the Genomic Sequence for the Autosomal Dominant Polycystic Kidney Disease (PKD1) Gene Predicts the Presence of a Leucine-Rich Repeat. The American PKD1Consortium (APKD1 Consortium). Hum. Mol. Genet. 4: 575-582.