Department of Molecular and Cellular Biology, College of Biological Sciences
To better understand the mechanisms and pathways underlying chromosome maintenance, we are focused on pathways that ensure the integrity of chromosomes during anaphase and how changes that lead to chromosome instability contribute to disease states (e.g, cancer). We currently are focused on two main projects:
Anaphase "Surveillance":This project examines the network of regulatory pathways and mechanisms that coordinate the faithful replication of chromosomes, their segregation in mitosis and the resolution of sister chromatids in anaphase. Our recent work suggests that a series of feedback loops help to ensure the damage-free resolution of sister chromatids. In particular, we are interested in the intersection between checkpoints and chromosome passenger proteins and how they combine to regulate a divers array of cellular activities in response to DNA replication stress, including spindle forces as well as membrane dynamics involved in nucleophagy.
Chromosome instability in cancer: These set of questions originated with our efforts to understand how cancer cells gain a chromosome instability (CIN) phenotype (one path to aneuploidy). We focused our early work on colorectal cancer as cells isolated from these cancers exhibit a high rate of mitotic errors. Our work demonstrated that one major contributor to chromosome instability comes from the initiating mutation in the tumor suppressor, adenomatous polyposis coli(APC). Though we remain interested in mechanisms that contribute to chromosome instability in cancers, our initial studies led us to focus on a paradox described by a number of labs studying cells with extra chromosomes, or aneuploidy. Namely, aneuploidy has been shown to lead to cell stress (e.g., proteotoxic and replication stress) that are generally not favorable for cell divisions, yet cancer cells divide and expand in the presence of these stresses. The answer to this paradox may lie in the ability of pre-cancer cells to be "reprogrammed" so that they adapt to tolerate the aneuploid state (as well as other cancer-associated changes). We term this reprogramming as cancer cell "adaption" and we propose that it involves a specific set of molecular changes that increase the likelihood that normal cells with sustain cancer-associated changes (i.e., a cancer "permissive" state).
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
Specialties / Focus
- Cell Biology
- Cancer Biology
- Cell Division and the Cytoskeleton
- Septin biology
- Chromosome Dynamics and Nuclear Function
- BIS104, Cell Biology (summer)
- MCB140L Cell Biology Lab, Winter
- BIS10, Everyday Biology
- MCB099/199, Introduction to research
- Seminar BCB215 Critical Reading, Spring
- Kaplan Lab: Life Sciences, 3137
- 1986 BS Biology Haverford College
- 1994 PhD University of California, San Francisco
- Post-doctoral studies, M.I.T. 1994-1999
Davies, A.E., Kortright, K., and Kaplan, K.B. (2015). Adenomatous polyposis coli mutants dominantly activate Hsf1-dependent cell stress pathways through inhibition of microtubule dynamics. Oncotarget.
Rozelle, D.K., Hansen, S.D. & Kaplan, K.B. Chromosome passenger complexes control anaphase duration and spindle elongation via a kinesin-5 brake. J. Cell BIol. 193, 285–294 (2011).
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
Thomas, S., and Kaplan, K.B. A Bir1p Sli15p kinetochore passenger complex regulates septin organization during anaphase. Mol Biol Cell. 2007; 18:3820-34.
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.