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Janet L. Paluh
Research Assistant Professor in Biology
CBIS Microscopy & Imaging Core Coordinator
Rensselaer Polytechnic Institute
Contact Information:
Office: (518) 276-4196
Lab: (518) 276-4189
paluhj@rpi.edu
Education:
Ph.D. Cancer Biology, Stanford University
Postdoctoral, University of California, Berkeley
Research Areas:
Funding: NSF 0616129: CBIS, Office of Research Start Funds
To successfully complete a cell cycle and maintain genomic continuity and cell viability, accurate segregation of chromosomes is essential. Cells decide to cycle in G1, duplicate centrosomes at G1/S, replicate DNA in S, then monitor for DNA damage, condense chromosomes and finish maturing spindle structures in the remaining interphase.
At mitotic onset a specialized, highly dynamic and transient structure, the mitotic spindle forms. It is an incredibly conserved device that allows the capture of chromosomes, alignment of them equatorially and coordination of their segregation to daughter cells before cytokinesis.
The beauty of the process has been observed for over a hundred years, yet we still struggle with mechanistic details. This is inevitable, since as we expand our knowledge we find an even more intricate layer of cell signaling mechanisms are at play. Towards understanding mitotic mechanisms my research applies timelapse 3D video microscopy, yeast genetics, molecular biology and biochemistry along with structural analysis of proteins. This research is funded in part by NSF Grant: 0616129.
Several projects are under investigation:
Mitotic Nanomachines- Kinesin-like Proteins (KLPs)
Fission yeast contain one quarter of the predicted KLPs present in humans, simplifying functional analysis. Our research investigates conserved Mitotic KLP families that include: essential Kinesin-10 (K10) Chromokinesin and spindle pole localized ubiquitous Kinesin-14A (K14), Pkl1p, and essential Kinesin-5 (K5), Cut7p. All KLPs bind tubulin in microtubules. We are defining tubulin sites for KLP/microtubule interactions, and the roles of K10, K14 and K5 KLPs in bipolar spindle assembly and in anaphase leading to mitotic exit. |
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Mitotic Exit Controls at Poles- Checkpoints and Ubiquitination
Mad2 is a spindle assembly checkpoint protein that regulates the transition from metaphase to anaphase A, helping to ensure mitotic fidelity. Mad2p blocks ubiquitin-mediated proteolysis needed to release cohesion between sister chromatids until appropriate. Previously it was expected that the work of Mad2p is completed by anaphase in all eukaryotes. My research identified an extended anaphase signaling pathway for Mad2p that operates through a microtubule organizing center (MTOC) at spindle poles and is integrated with asymmetric mitotic exit signals for cytokinesis. |
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The Microtubule Organizing Center (MTOC)
The MTOC is a highly conserved macromolecular structure at yeast spindle pole bodies and metazoan centrosomes. It is required for nucleation of spindle microtubules and is a signaling center for cell cycle functions. We are defining core and transient protein interactions of the MTOC and spindle parameters and signaling pathways regulated. |
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Tubulin Structure and Function
Yeast contain single β-tubulin and γ-tubulin genes and two α-tubulin genes. In multi-cellular eukaryotes the genetic profile is more complex and includes additional isotypes and tubulin families. We apply structure/function analysis of tubulins towards improved drug targeting and cancer therapies. |
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Human Embryonic Stem Cells ( HuESCs)
I am trained in growth, maintenance and differentiation of HuESCs. My research is aimed at understanding the microenvironment of HuESCs in order to regulate self-renewal with maintained pluripotency or direct differentiation upon defined pathways. Such knowledge is critical to controlling the microenvironment in vitro and in vivo and will provide insights to cancer stem cells. |
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Selected Publications:
1. Shih, P., Stromberg, M., Filopei, J. and J.L. Paluh (2007) Checkpoints and Asymmetry: Integrating spindle events with mitotic signaling from metaphase to telophase. Recent Research Developments in Molecular Biology. Invited review in preparation.
2. Rodriguez, A.S., Batac, J., Killilea, A.N., Filopei, J., Simeonov, D.R., Lin, I. and J.L. Paluh (2008) Protein complexes at the microtubule organizing center regulate bipolar spindle assembly. In press, Cell Cycle.
3. Mayer, C.L., Filopei, J., Batac, J., Alford, L. and J.L. Paluh (2006) An extended signaling pathway for Mad2p in anaphase includes microtubule organizing center proteins and multiple motor-dependent transitions. Cell Cycle. 5: 1456-1463
4. Paluh, J.L., Killilea, A.N., Detrich, H.W., and Downing, K.H. (2004). Meiosis-specific failure of cell cycle progression in fission yeast by mutation of a conserved beta-tubulin residue. Molec. Biol. Cell 15: 1160-1171.
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