Research interest
The research within the group of Dr. John Collard is concentrated on signalling pathways that control cell polarization and invasion and metastasis of tumour cells. Using the proviral tagging method his group identified the invasion-inducing Tiam1 gene, which encodes an activator (GEF) of the Rho-like GTPase Rac. Proteins of the Rho family, which include Cdc42, Rac1 and RhoA, regulate signalling pathways that control the remodelling of the actin cytoskeleton in response to receptor stimulation. Collard’s group found that Rho-like proteins play essential- as well as regulatory roles in integrin-mediated cell-matrix interactions, in cadherin-based cell-cell adhesions, in cell polarization and in migration and invasion of normal and tumour cells.
Within the group of John Collard various projects are going on that include: studies on the role of Rho family proteins in processes of cell polarization, cell-cell adhesion, cell-matrix adhesion, and cell migration; studies on the cross talk between signalling pathways mediated by Ras- and Rho- like GTPases; studies on the function of the Rac activator Tiam1 by using Tiam1 transgenic- and knock-out animals; studies on the function of Tiam1 and the polarity protein Par 3 by using transgenic- and knock-out animals; studies on the function of Tiam1 and Par3 in tumorgenicity and polarity processes.
Vacancies
Within the group there are also opportunities for applicants to continue their research by obtaining their own fellowships. For further details on ongoing research or positions see NKI website, or contact John G. Collard (j.collard@nki.nl).
Key publications
A. Hadjo-Milasinovic, Z. Moeva, J.G. Collard. Rac3 inhibits adhesion and differentation of neuronal cells by modifying Git1 downstream signaling. J. Cell Science, 2009; 122: 2127-36
A. Gérard, R.A. van der Kammen, H. Janssen, S.I. Ellenbroek, J.G. Collard. The Rac activator Tiam1 controls efficient T-cell trafficking and route of trans-endothelial migration. Blood, 2009, 113: 6138-47
S. Iden, J.G. Collard. Cross-talk between small GTPases and polarity proteins in cell polarization. Nat Rev Mol Cell Biol, 2008; 9:846-859
D.M. Pegtel, S.I. Ellenbroek, A.E. Mertens, R.A. van der Kammen, J. de Rooij, J.G. Collard. The par-tiam1 complex controls persistent migration by stabilizing micortubule-dependent front-rear polarity. Curr. Biol 2007, 17;1623-1634.
A. Gerard , A.E. Mertens, R.A. van der Kammen, J.G. Collard. The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization. J Cell Biol 2007; 176:863-875.
A.E. Mertens, D.M. Pegtel, J.G. Collard. Tiam1 takes PARt in cell polarity. Trends in Cell biology, Epub 2006 16(6):308-16.
A.E. Mertens, T. Rygiel, C. Olivo, R.A. van der Kammen, J.G Collard. The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex. J. Cell Biol. 2005, 170: 1029-1037.
I.H.L. Hamelers, C. Olivo, A.E.E. Mertens, D.M. Pegtel, R.A. van der Kammen, A. Sonnenberg, J.G. Collard. The Rac activator Tiam1 is required for a3b1-integrin-mediated laminin 5 deposition, cell spreading and cell migration. J. Cell Biol, 2005, 171: 871-881.
A. Malliri, R.A.Van der Kammen, K.Clark, M.Van Der Valk, F.Michiels, J.G.Collard. Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours. Nature, 2002, 417: 867-871.
F.N. van Leeuwen, S. van Delft, H E. Kain, R. A. van der Kammen, J.G. Collard. Rac regulates phosphorylation of the myosin-II heavy chain, actinomyosin disassembly and cell spreading. Nature Cell Biol, 1999, 1: 242-248.
J.C. Stam, F. Michiels, R.A. van der Kammen, W.H. Moolenaar, J.G. Collard. Invasion of T-lymphoma cells: cooperation between Rho family GTPases and LPA receptor signaling. EMBO J, 1998, 17: 4066-4074.
E.E. Sander, S. van Delft, J-P ten Klooster, T. reid, R. van der Kammen, F. Michiels, J.G. Collard. Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase. J Cell Biol, 1998, 143: 1385-1398.
P.L. Hordijk, J-P ten Klooster, R.A. van der Kammen, F. Michiels, L.C.J.M. Oomen and J.G. Collard: Inhibition of invasion of epithelial cells by Tiam1-Rac signaling. Science, 1997, 278: 1464-1466.
F. Michiels, G.G.M. Habets, J. Stam, R.A. van der Kammen, J.G. Collard. A role for Rac in Tiam1-induced membrane ruffling and invasion. Nature, 1995, 375: 338-340.
G.G.M. Habets, W.H.M. Scholtes, D. Zuydgeest, R. van der Kammen, J.C Stam, A. Berns, J.G. Collard. Identification of an invasion-inducing gene, Tiam1, that encodes a protein with homology to GDP-GTP exchangers for RHO-like proteins. Cell, 1994, 77: 537-549.
More publications by John Collard on PubMed.
Biographic sketch
John G. Collard completed his Masters with honours at the Faculty of Science of the University of Nijmegen in 1971. He subsequently finished his PhD studies at the same University in 1976 with the thesis entitled: A comparative study of the normal and transformed cell surface with the lectin Concanavalin A. The Netherlands Cancer Institute in Amsterdam has been key to John Collard’ scientific career, where he has been appointed since 1976 initially at the department of Experimental Cytology and later as a group leader in the Division of Cell Biology. In 1977, he was a visiting scientist at The Weizmann Institute of Science, department of Membrane Biology, Rehovot, in Israel.
Co-workers
Iden, Sandra PhD Postdoc
Ellenbroek, Saskia MSc Graduate student
Mertens, Sander MSc Graduate student
Schaefer, Ronny Technical staff