John W.R. Copeland, Ph.D.
Associate Professor
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Degrees
Ph.D. Molecular and Medical Genetics, University of Toronto, Canada, 1997
B.Sc. with first class honours, Genetics, University of Alberta, Canada, 1989
Contact info:
RGN, Rm. 3155
Phone: 562-5800 x8641
Email: jcopelan@uottawa.caResearch Interests:
Our laboratory studies the function of the formin homology family of cytoskeletal remodeling proteins. These proteins carry out both structural and signaling roles to govern cell morphology through their effects on actin and microtubule dynamics. Using cultured human cells as a model, we study the cellular roles of formins by applying a powerful combination of molecular, cellular and microscopy-based assays.
Our current major projects include:Formins and the endothelial shear stress response
Shear stress is induced by the frictional drag caused by the flow of blood over the surface of the endothelium. This induces activation of a unique atheroprotective response in endothelial cells which results in a dramatic remodeling of the endothelial cell cytoskeleton. The cellular morphology induced by shear in endothelial cells is very similar to that seen in cells expressing constitutively-active formin derivatives. We are working to systematically knockdown expression of each formin expressed in endothelial cells in an effort to determine the requirement for formin activity in this unique process.
INF1 and cell polarity
INF1 is a novel formin that is unique in its ability to bind directly to the microtubule (MT) network. Through its C-terminal MT binding domain and N-terminal FH2 domain, INF1 is able to connect the two major cytoskeletal systems: actin filaments and the microtubule network. Our results suggest that this aspect of INF1 activity is essential for normal assembly of the Golgi apparatus. We are investigating the requirement for INF1 in Golgi assembly and its downstream effects on cell polarity.
FMNL2 and metastasis
The Diaphanous-Related Formin FMNL2 is upregulated in metastatic colorectal cancer cells and knockdown of FMNL2 expression in melanoma cells inhibits invasion in vitro. FMNL2 mRNA is predicted to undergo multiple alternative splicing events. Our preliminary data suggests that an over-representation of one of these isoforms is associated with increased invasiveness. We are characterizing the biochemical properties of the “invasive” FMNL2 isoform to determine how this may affect FMNL2’s ability to drive invasion both in vitro and in vivo.
Grants
| Heart and Stroke Foundation | 2006-2013 |
| CIHR Operating Grant | 2010-2015 |
| CFI New Opportunities Award | 2004-2008 |
Publications:
Chan, M.W.C.; Chaudary, F.; Lee, W.; Copeland, J.W. and C.A. McCulloch (2010). Force-induced Myofibroblast Differentiation through Collagen Receptors is Dependent on Mammalian Diaphanous (mDia). J Biol Chem 285(12):9273-81
Kitzing, T.M.; Wang, Y.; Copeland, J.W.; Pertz, O. and Robert Grosse (2010). Formin-like 2 (FMNL2) drives amoeboid invasive cell motility downstream of RhoC. Oncogene 29: 2441-2448.
Young, K.G. and Copeland, J.W. (2010). Formin Signaling Pathways. BBA-MCR
1803:183-190
Vaillant, D.; Copeland, S.J.; Davis, C.; Thurston, S.; Abdennur, N. and Copeland, J.W. (2008). Interaction of the N- and C-terminal auto-regulatory domains of FRL2 does not inhibit FRL2 activity. JBC: 28;283(48):33750-62.
Young, K.G.; Thurston, S.; Copeland, S.J.; Smallwood, C. and Copeland, J.W. (2008). INF1 is a novel microtubule-associated formin. Mol Biol Cell, 19(12):5168-80
Copeland, S.J.; Green, B.J.; Burchat, S.; Papalia, G.A.; Banner, D. and Copeland, J.W. (2007) The DID/DAD Interaction is able to Mediate Heterodimerisation Between mDial and mDia2. JBC 282:30120-30.
Johnston Jr., R.J.; Copeland, J.W.; Fasnacht, M.; Etchberger, J.F.; Liu, J.; Honig, B. and Hobert, O. (2006) An unusual Zn finger/FH2 domain protein controls a left/right asymmetric neuronal fate decision in C. elegans. Development 133:3317-3328.
Copeland, J.W.; Copeland, S.J. and Treisman, R. (2004) Homo-oligomerisation is essential for F-actin assembly by the FH2 domain. JBC 279(48):50250-50256.
Grosse, R.; Copeland, J.W.; Newsome, T.; Way, M. and Treisman, R. (2003) A role for VASP in RhoA-Diaphanous signalling to actin dynamics and SRF. EMBOJ 22: 3050-3061.
Copeland, J.W. and Treisman, R. (2002) The Diaphanous Related Formin mDia1 controls Serum Response Factor (SRF) activity through its effects on actin polymerisation. MBC 13(11): 4088-4099.
Geneste, O.; Copeland, J. and Treisman, R. (2002) LIM Kinase and Diaphanous cooperate to regulate Serum Response Factor and actin dynamics. JCB 157: 831-838.
Schwartz, C.J.E.; Sampson, H.M.; Hlousek, D.; Percival-Smith, A.; Copeland, J.W.R.; Simmonds, A.J. and Krause, H.M. (2001). FTZ-Factor1 and Fushi tarazu interact via conserved nuclear receptor and coactivator motifs. EMBOJ 20: 510-519.
Sotiropoulos, A.; Gineitis, D.; Copeland, J. and Treisman, R. (1999). Signal-Regulated Activation of Serum Response Factor is Mediated by Changes in Actin Dynamics. Cell 98: 159-169.
Guichet, A.; Copeland, J.W.R. (co-first author); Erdelyi, M.; Hlousek, D.; Zavorsky, P.; Ho, J.; Brown, S.; Percival-Smith, A.; Krause, H. and Ephrussi, A. (1997). The nuclear receptor homologue FTZ-F1 and the homeodomain protein FTZ are mutually dependent co-factors. Nature 385: 548-552.
Copeland, J.W.R.; Nasiadka, A.; Dietrich, B. and rause, H.M. (1996). Patterning of the Drosophila embryo by a homeodomain deleted Ftz polypeptide. Nature 379: 162-165.
Fellowships and Awards:
Postdoctoral:
Burroughs-Welcome Career Development Award
EMBO Long-term Fellowship
Graduate:
University of Toronto Open Fellowship
NSERC Graduate Fellowship
MRC Graduate Fellowship
Connaught Graduate Fellowship
Undergraduate:
Dean's Silver Medal in Science
Robert J. Tegler Scholarship
Alberta Society of Professional Biologist's Award
Province of Alberta Award