Chair, Department of Systems Biology
Warren Alpert Building, Room 536
200 Longwood Avenue
Boston, MA 02115
Lab Members: 17 postdoctoral fellows, 1 graduate student
Our lab has focused on understanding cell morphogenesis, cell proliferation, and cell signaling by combining biochemical, cell biological, and embryological approaches. We are also interested in the evolution of vertebrates through studies of hemichordate development and genomics. We have attempted to ask what controls cell motility and polarity on a molecular level, how is information concerning cell morphology communicated to the cell from external sources, and how is cell size regulated. We have concentrated on Cdc42 and Rac-1 dependent actin nucleation in extracts and have identified novel components downstream of these small GTPases likely to be involved in lamellopodia or filopodia formation, membrane potrusions required for directional cell motility. We are also interested in growth control and cell cycle coordination.
Our studies of cell proliferation concern primarily the regulation of several important proteolysis systems in mitosis and G1. We have used both Xenopus and mammalian cultured cell extracts for the study of the anaphase promoting complex/cyclosome (APC), which controls the degradation of important regulators of anaphase, including cyclin and the anaphase inhibitor, Securin. APC serves as a nexus for cell cycle checkpoint controls and for proper regulation of chromatid separation. We have purified many of the components involved in cell cycle progression and our current aim is to understand how these serve to coordinate the sequence of events in mitosis and in the G1 phase of the next cell cycle. Recently, we have developed in vitro systems for somatic cells. We are utilizing a novel mass spectrometric based quantification system to accurately define the order of events in mitosis and G1, and to identify novel components of the cell cycle and differentiation machinery. We have pioneered methods for studying cell growth and cell size.
Our studies in signal transduction and in developmental biology concern early patterning and motility events in gastrulation, as well as a modeling based understanding of the Wnt-signaling and BMP pathways. In the hope of identifying the evolutionary origins of vertebrate patterning, we have examined the hemichordate, Saccoglossus, which shows several key features of the vertebrate and arthropod organization. We have combined developmental and genome studies in this organism to better understand the origins of the chordate nervous system and the Spemann Organizer. We are interested in comparative genomics of deuterostomes. We have used mathematical models for signaling pathways to predict novel features. We have an interest in using developmental systems for studying drug action through systems approaches.
Lee K, Gallop JL, Rambani K, Kirschner MW. Self-assembly of filopodia-like structures on supported lipid bilayers. Science. 2010 Sep 10;329(5997):1341-5. PMCID: PMC2982780.
Goentoro L, Kirschner MW. Evidence that fold-change, and not absolute level, of beta-catenin dictates Wnt signaling. Mol Cell. 2009 Dec 11;36(5):872-84. PMCID: PMC2921914.
Tzur A, Kafri R, LeBleu VS, Lahav G, Kirschner MW. Cell growth and size homeostasis in proliferating animal cells. Science. 2009 Jul 10;325(5937):167-71. PMCID: PMC2905160.
Book: Kirschner, MW and Gerhart, JC. The Plausibility of Life: Resolving Darwin’s Dilemma. New Haven: Yale University Press, 2005. ISBN: 9780300108651; ISBN-10: 0300108656.
For a complete listing of publications click here.
Last Update: 7/26/2012