Denis A. Larochelle
Associate Professor of Biology
Program Director, Biochemistry & Molecular Biology
Department of Biology
Biochemistry and Molecular Biology Program
15 Maywood St.
Worcester, MA 01610-1477
Office: 334 Lasry Center for Bioscience; Lab: 322
Ph.D. Stanford University
M.S. University of New Hampshire, Durham
B.A. University of New Hampshire, Durham
Current Research and Teaching
Cytokinesis, the process by which a cell constricts at the equator to ultimately divide into two daughter cells remains poorly understood. My primary interest has been to identify the proteins/genes involved in both the mechanics and the regulation of this process. To achieve this goal my lab uses the cellular slime mold Dictyostelium discoideum. Using Dictyostelium a molecular genetic screen was developed to identify the genes required for cytokinesis. Several genes were subsequently identified and we are in the process of describing how these genes participate in the regulation of cytokinesis. One of these genes codes for a novel small GTP-binding protein of the ras superfamily. Initial characterization of mutant cell lines containing disruptions in this gene, named racE, has revealed racE to be essential solely for cytokinesis, and all other aspects of Dictyostelium biology2 appear to be normal in these cells. A second gene has recently been identified which also functions in cytokinesis. We are still in the process of characterizing this gene but limited sequence analysis reveals strong homology to the mouse beige gene and the human gene responsible for the Chediak-Higashi syndrome. We are now in the process of trying to understand the cell biology and biochemistry of how these genes function in cytokinesis. Future work will include further characterization of these genes, as well as continuation of the screen to identify additional genes involved in cytokinesis.
Mana-Capelli,S., R. Gräf and D.A. Larochelle.(2010). Dictyostelium centrin B localization during cell cycle progression. Communicative & Interactive Biology 3:1, 1-3: January/February 2010; Landes Bioscience
Mana-Capelli, S., R. Gräf, and D.A. Larochelle. (2009). Dictyostelium discoideum CenB is a bona fide centrin essential for nuclear architecture and centrosome stability. Eukaryotic Cell 8:
Hiong, H.,F. Rivero, U. Euteneuer, S. Mondal, S. Mana-Capelli, D.A. Larochelle, Vogel, B. Gassen, and A. Noegel. (2008). Sun-1 connects the centrosome to chromatin and ensures genome stability. traffic 9:1-17.
Agarval, M.,N. Guerin, and D.A.Larochelle (2004). Chimeric analysis of the small GTPase RacE in cytokinesis sygnaling in Dictyostelium discoideum. Experimental Cell Research 295:226-235.
Abysalh, J.C.,LL.Kuchnicki and D.A.Larochelle (2002) The identification of Pats1, a novel gene locus required for cytokinesis in Dictyostelium discoideum. Molecular Biology of the cell 14:14-25
Guerin, N. and D.A.Larochelle (2003). A user's guide to restriction enzyme-mediated integration in Dictyostelium. (Accepted for publication in a special issue of the Journal of Muscle Research and Cell Motility dedicated to Dictyostelium research.)
Agarwal, M., D.J.Nelson, and D.A. Larochelle (2002). The three dimensional model of Dictyostelium discoideum RacE based on the human RhoA-GDP crystal structure. Submitted to the Journal of Molecular Graphics and Modeling 21:3-18.
Neicu, T., A.Pradham, D.A. Larochelle, and A. Kudrolli (2000). Extinction transition in bacterial colonies under forced convection. Physical Review E62(1):1059-1062.
Larochelle, D.A., N. Gerald, and A. De Lozanne (2000). Molecular analysis of racE function in Dictyostelium . Microscopy Research and Techniques-The Biology of Cytokinesis 49(2):145-151.
Kwak E., N. Gerald, D.A. Larochelle, K.K. Vithalani, M. Niswonger, and A. De Lozanne (1999). LvsA, a protein related to the mouse beige protein, is essential for cytokinesis in Dictyostelium . Molecular biology2 of the Cell 10:4429-4439.
Vithalani, K.K., C.A. Parent, E.M. Thorn, M. Penn, D.A. Larochelle, P.N. Devreotes, and A. De Lozanne (1998). Identification of Darlin, a Dictyostelium protein with Armadillo -like repeats that binds to small GTPases and is important for the proper aggregation of developing cells. Molecular Biology of the Cell 9:3095-3106.
Larochelle, D.A., K.K. Vithalani and A. De Lozanne (1997). The role of Dictyostelium racE in cytokinesis: Mutational analysis and localization studies by use of green fluorescent protein. Molecular Biology of the Cell 8:935-944.
Larochelle, D.A., K. Vithalani and A. De Lozanne (1996). A novel member of the rho family of small GTP-binding proteins is specifically required for cytokinesis. J. Cell Biology 133:1321- 1329.
Burns, C.G., D.A. Larochelle, H. Erickson, M. Reedy and A. De Lozanne (1995). Single-headed myosin II acts as a dominant negative mutation in Dictystelium . Proc. Natl. Acad. .Sci. USA 92:8244-8248.
Larochelle, D.A. and D. Epel (1993). Myosin heavy chain dephosphorylation during cytokinesis in dividing sea urchin embryos. Cell Motility and the Cytoskeleton 25(3):369-380.
2009 Nuclea Biomarkers, LLC (DAL, PI). Title: Dictyostelium-based screen for novel drugs. Funding period June 1, 2009-May 31, 2010; renewable for three years. $125,000 per year.2002-2005 National Science Foundation Grant, $309,028 for "Characterization of a novel regulatory protein required for cytokinesis".
2000-2001 National Science Foundation Multi-User Grant, $42,454 for "A Microscopy imaging system for the Department of Biology at Clark University"(co-PI with D. Hibbett, T. Lyerla, and J. Thackeray).
1999-2002 National Institutes of Health AREA Grant, $110,325 for "The racE pathway in the regulation of cytokinesis".