About Us > Faculty & Staff > Faculty > Janet Paluh
Associate Professor of Nanobioscience
- Postdoctoral Fellow, University of California, Berkeley, Berkeley, CA, 2001
- Ph.D., Cancer Biology, Stanford University, Stanford, CA 1996
- Research Assistant Professor, Department of Biology, Rensselaer Polytechnic Institute, Troy, NY
Areas of research:
- Nanomotors and Microtubules
- Intracellular machines
- Mitotic mechanisms
- Cell Cycle signaling networks
- Pluripotent stem cells and nuclear reprogramming
- In vitro 3D cell patterned architectures
The research in Dr. Paluh's lab has a dual focus to understand and biomimic intracellular signaling networks and the nanoscale machines they regulate as well as to apply new advanced cell patterning technologies towards 3D tissue assembly in organ development. Research in Dr. Paluh's lab has advanced the field of mitosis through discovery of novel mechanisms in spindle assembly including structure and function of the microtubule organizing center (MTOC) complex and specialization of motor protein functions. In stem cell frontier research projects include derivation of new minority source pluripotent stem cell lines, analysis of stem cell self renewal and cell specification, signaling events in hypoxia, and in vitro design of functional 3D cell architectures towards therapeutic goals in organ repair. This work applies genetic strategies, timelapse 3D microscopy, biochemistry, molecular biology and bioinformatic/ structural and systemic approaches, stem cell biology and collaborative efforts in tissue engineering for development of idealized synthetic 4D spatiotemporal niches.
Cellular Machines and Multicellular Design Principles
- Cellular Motors and Microtubules in Nanofabrication. The mitotic spindle is an ideal self-assembling and regulating machine for biomimicry applications. On a simple scale Kinesin-like microtubule motor proteins and microtubules provide an ideal source for tip-based nanofabrication in a synthetic environment. More complex applications include generation of a microtubule organizing center macromolecular machine for synthesis and organization of 25nm microtubules in an artificial environment.
- Niche design. Directed differentiation of stem cells, organ development and high throughput applications with stem cells require collaborative efforts in nanoengineering that combine cell expertise with biomedical, chemical and materials science engineering to develop 4D architectures that mimic the cellular environment in a spatiotemporally reactive manner.
The Mitotic Spindle Apparatus
- Kinesin-like proteins (Klps) and microtubules. Klps are master regulators of the microtubule cytoskeleton coordinated to perform diverse roles in transport, signaling and cytoskeleton remodeling. Fourteen conserved Klp families exist, but in varied combinations in eukaryotes indicating inherent flexibility in motor protein task relationships. Work from the Paluh lab is defining functional determinants of Klps and tubulins fundamental to understanding in vivo roles and to their improved use in bioengineering applications.
- The MTOC Interactome. Microtubule Organizing Centers (MTOCs) are macromolecular complexes used in a variety of diverse cellular roles including spindle assembly or cilia function. The MTOC is a site of microtubule growth, organization and dynamics and a signaling hub. Unique reagents in the Paluh lab are enabling rapid discoveries that define at the molecular level conserved structural and functional parameters as well as regulation of this complex by temporally associated proteins.
- Asymmetric processes & checkpoints. To avoid fatal system failures leading to cell death cells monitor cell cycle progression. Such checkpoints overlay underlying cellular mechanisms to provide a fail-safe mechanism. In multi-cellular eukaryotes checkpoints often operate on a timer due to the greater consequences of a failed restart. Research in the Paluh lab investigates interlinked checkpoint and asymmetry mechanisms in mitosis. Asymmetry in development helps to define daughter cell fates and will be critical in design of synthetic 4D spatiotemporal cellular niches.
Pluripotent Stem Cells:
- Human embryonic stem cells. hESCs offer unlimited potential for human therapies. Limited racial diversity exists in current lines. The Paluh lab recently received a NYSTEM ~$1M award for derivation of new hESC lines from minority populations. This work in collaboration with renowned stem cell expert, Dr. Jose Cibelli, is applying new strategies to optimize successful derivations. Fully characterized lines (pluripotency, transcriptome, proteome and epigenome) apply NIH 2009 guidelines and will be banked for scientific community, biomedical and industry use.
- Development of an optimized synthetic niche. Our knowledge of the the ideal stem cell microenvironment in culture remains rudimentary and currently inadequate for stem cell expansion, directed differentiation, high throughput screening, or biomedical therapies. The Paluh lab is investigating how environmental gases, scaffolds and cell patterning affect stem cell signaling pathways to be able to apply this knowledge towards advancing therapeutic stem cell applications.
- Nuclear reprogramming. The generation of induced pluripotent stem cells (iPSCs) remains challenging and has yet to be optimized in regard to epigenetic profile, limiting genomic alterations and avoiding side affects of accelerated aging. The Paluh lab is interested in key cell cycle signaling pathways regulating iPSC populations during reprogramming.
Recent Speaker Events
- 2010, Panelist Project Lead the Way, Nano'izing K-12
- 2010, Keynote, Columbia High School Science Conference, E. Greenbush, NY
- 2009, Biophysical Society meeting Minisymposium, Microtubular Motors, Boston, MA
- 2008, EMBO Conference on Centrosomes and Spindle Pole Bodies, Heidelberg, Germany
- 2008, North America Pombe Meeting, Los Angeles, CA
- 2008, American Cancer Society, Scientific Speaker, Relay for Life, RPI, Troy, NY
Special Interest Meetings and Training
Human Embryonic Stem Cell Methods, CHOC, WiCell, Stanford
Automated Cell Culture Applications to Stem Cells
In vitro Analyses of Cell/Scaffold Products
Interagency Modeling and Analysis Group
IEEE Standards Association: NanoCom working group
- Paluh, J.L., Dai, G., and Chrisey, D.B. (2011) In search of the Holy Grail: Engineering the stem cell niche. European Pharmaceutical Review. 16(2):28-33
- Stansfield, H.E., Gasimli, L., Nairn, A.V., Li, B., Liu, H., Paluh, J.L., Yang, B., Saunders, M.J., Dordick J.S., Moreman, K.W., and R. J. Linhardt (2011) Structural remodeling of proteoglycans on retinoic acid-induced differentiation of NCCIT cells. in submission to J. Biol. Chem.
- Seo, L., Kenny, K., Zhou, R., Cruz, L., Fine, R. and J.L. Paluh (2010). Conserved and divergent mechanisms of the microtubule organizaing center γ-tubulin small complex (γ-TuSC). Manuscript in preparation Cell Cycle.
- Simeonov, D.R., Kenny, K., Moyer, A., Seol, L. Allen, J. and J.L. Paluh (2009) Distinct Kinesin-14 mitotic mechanisms in spindle bipolarity. Cell Cycle 8(21), 3571-3583. * featured in News and Views, Spindle function in yeast: a human motor to the rescue. Cell Cycle. 8(21): 3452-3454.
- Paluh, J.L. (2008) Sentinels of DNA integrity in stem cells. Cell Cycle 7(18): 2779-2780.
- Paluh, J.L. (2008) Kinesin-14 leaps to pole position in bipolar spindle assembly. Chinese Journal of Cancer, 27(9): 1-5.
- Rodriguez, A. S., Batac, J., Filopei, J., Killilea, A. N., Allen, J. and J.L. Paluh (2008) Protein complexes at the microtubule organizing center regulate bipolar spindle assembly. Cell Cycle. 7(9): 1246-1253.
- 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.
- Paluh, J.L., Killilea, A. N., Detrich III, W., and K. Downing (2004) Meiosis-specific failure of cell cycle progression in fission yeast by mutation of a conserved β-tubulin residue. Mol. Biol Cell. 15: 1160-1171.
- Paluh, J.L., Nogales, E., Oakley, B.R., McDonald, K., Pidoux, A.L., and W. Z. Cande (2000) A mutation in γ-tubulin alters microtubule dynamics and organization and is synthetically lethal with the Klp Pkl1p. Mol. Biol. Cell 11: 1225-1239.