Kenneth Kaplan
Professor
kbkaplan@ucdavis.edu
Molecular & Cellular Biology
Office
Briggs 204B
754-5044
1994
PhD
University of California, San Francisco
1986
BS
Haverford College
Biology
My laboratory is interested in understanding how chromosomes are accurately segregated during mitosis. We study the normal events of mitosis using the model organism, the budding yeast Saccharomyces cerevisiae. We study abnormal mitotic events associated with human disease using colorectal cancer as a model.
To understand how chromosome segregation is coordinated with anaphase events, we have focused on kinetochore-passenger complexes. Kinetochore-passenger complexes transit between kinetochores and the anaphase spindle where they are believed to coordinate chromosome movements with events in anaphase. We are interested in how kinetochore-complexes assemble during anaphase, which anaphase events are coordinated by kinetochore-passenger complexes and the mechanisms by which these complexes regulate anaphase events to ensure their proper order (e.g., anaphase spindle elongation and cytokinesis).
To understand how chromosome segregation is compromised in human cancers, we are examining chromosome instability (CIN) in colorectal tumor cells. We have found that mutations in the tumor suppressor gene, adenomatous polyposis coli (APC), contribute to failures in chromosome segregation. We have shown that mutations in APC compromise the ability of microtubules to make plus-end attachments in mitotic cells. Our finding that this phenotype is genetically dominant has important implications for patients that have a single mutant copy of APC. We are currently exploring the mechanisms by which mutations in APC compromise plus-end microtubule attachment and how this cellular phenotype may contribute to the progression of colorectal cancer.
Genetics
Microbiology
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Rodrigo-Brenni, M., Thomas, S., Bouck, D. Kaplan, K.B., Sgt1p and Skp1p modulate the assembly and turnover of CBF3 complexes required for proper kinetochore function. Mol Biol Cell. 2004 Jul;15(7):3366-78.
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Lingelbach, L.B., and Kaplan, K.B., The transient interaction between Sgt1p and Skp1p during CBF3 assembly is regulated by HSP90 chaperones. Mol Cell Biol. 2004 Oct;24(20):8938-50.
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Green, R. A., and Kaplan, K. B. (2004). Chromosome instability in colorectal tumor cells is associated with defects in microtubule plus-end attachments caused by a dominant mutation in APC. J Cell Biol 163, 949-961.
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Gillis, A.N., Thomas, S., Hansen, S.D., Kaplan, K.B., A novel role for the CBF3 kinetochore-scaffold complex in regulating septin dynamics and cytokinesis. The Journal of Cell Biology; Dec. 5th, 2005; 171(5)
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Green, R.A., Wollman, R., Kaplan, K.B., APC and EB1 Function Together in Mitosis to Regulate Spindle Dynamics and Chromosome Alignment. Mol Biol Cell, 2005 Oct;16(10):4609-22
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Catlett, M.G., Kaplan, K.B., Sgt1p is a unique co-chaperone that acts as a client-adaptor to link Hsp90 to Skp1p, Nov 3, 2006; 281(44):33739-48.
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Thomas, S., and Kaplan, K.B. A Bir1p Sli15p kinetochore passenger complex regulates septin organization during anaphase. Mol Biol Cell. 2007; 18:3820-34.
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Caldwell, C. Green, R.A., Kaplan, K.B., APC mutations lead to cytokinetic failures in vitro and tetraploid genotypes in Min mice, The Journal of Cell Biology 178(7): 1109-20,2007
BIS
104
Cell Regulation and Function
Winter
CDB
200
Methods in Fluorescence Microscopy
Fall
MCB
138
The biolology of cancer therapeutics
Fall