Molecular Control of Cell Division
Dr. Stumpff graduated with a B.S. in Biology from Eckerd College in 1998. He received his Ph.D. in Molecular, Cellular and Developmental Biology from the University of Colorado, Boulder in 2004 and was a postdoctoral fellow at the University of Washington, Seattle from 2005-2011. Dr. Stumpff joined the faculty in the Department of Molecular Physiology and Biophysics at the University of Vermont in 2011. He is also a member of the Vermont Cancer Center and a Special Fellow of the Leukemia and Lymphoma Society.
The Stumpff lab utilizes a combination of cutting edge quantitative cell biology and single molecule approaches to investigate the molecular mechanisms controlling cell division and how they relate to human disease.
Cell division, in its simplest terms, is the process by which one cell becomes two. Cellular proliferation is necessary for the survival and development of all organisms, and a key objective during the division process is to equally segregate one complete set of replicated chromosomes to each daughter cell. This step is dependent on the microtubule-based mitotic spindle, which acts to capture, align and then partition replicated chromosome pairs. Mitotic spindle function must be tightly regulated to prevent chromosome segregation errors and the production of aneuploid cells, i.e. cells with the wrong number of chromosomes. Aneuploidy is a hallmark of both solid tumor and blood cancer cells, is implicated in the initiation and development of cancer, is a leading cause of human miscarriages and is the cause of monosomy and trisomy syndromes (e.g. Turner’s syndrome, Down’s syndrome, Edward’s syndrome and Patau syndrome). Thus, elucidating the mechanisms controlling spindle assembly and function is an important step towards a molecular understanding of a wide range of human health disorders.
The key to understanding how the mitotic spindle carries out chromosome segregation is to determine how the dynamics of the microtubules that comprise it are controlled. Subsets of microtubules within the spindle act as force generators that physically push and pull the chromosomes to their proper positions within the cell, while others function to orient the spindle within the cell, facilitate intracellular signaling or provide structural integrity. All of these functions rely on the regulation of spindle microtubule assembly and disassembly. While microtubules are intrinsically dynamic, it remains unclear how microtubule assembly and disassembly are spatially and temporally controlled within the spindle to ensure accurate segregation of the genome. Our long-term goal is to understand the mechanisms that provide this control.
We are currently investigating a number of fundamental questions related to understanding the mechanisms controlling chromosome segregation and spindle function during cell division:
1. How do molecular motor proteins control the lengths of different subpopulations of mitotic spindle microtubules?
2. What mechanisms mechanically regulate attachments between chromosomes and spindle microtubules?
3. How does the spatial control of mitotic chromosome movements contribute to the accurate segregation of the genome and its 3D organization during interphase?
4. How do the mitotic functions of the Shwachman Bodian Diamond syndrome protein impact bone marrow failure and leukemia predisposition in SDS patients?
Molecular Control of Cell Division
Bissonette S, Stumpff J. Quantifying Mitotic Chromosome Dynamics and Positioning. J Cell Physiol. 2014 Mar 28.
Stumpff J, Ghule PN, Shimamura A, Stein JL, Greenblatt M. Spindle microtubule dysfunction and cancer predisposition. J Cell Physiol. 2014 Jun 6.
Stumpff, J., Measuring microtubule thickness: An exercise in cooperativity. Dev Cell. 2012 July 17; 23(1): 1-2.
Stumpff, J., Wagenbach, M., Franck, A., Asbury, CL. and Wordeman, L. Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension Dev Cell. 2012 May 15; 22(5): 1017-1029.
Stumpff, J, Du, Y, English, CA, Maliga, Z, Hyman, AA, Asbury, C, Wordeman, L and Ohi, R. A tethering mechanism controls the processivity and kinetochore-microtubule plus-end enrichment of the kinesin-8 Kif18A. Mol Cell. 2011 Sep 2;43(5):764-75.
Stumpff, J., von Dassow, G., Wagenbach, M., Asbury, C. and Wordeman, L. The kinesin-8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment. Dev Cell. 2008 Feb;14(2):252-62.
* indicates equal contribution
Department of Molecular Physiology & Biophysics
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Lab: Given E215
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