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Janet Paluh
Dr. Janet Paluh
Associate Professor of Nanobioscience

Degrees:

  • Postdoctoral Fellow, University of California, Berkeley, Berkeley, CA, 2001
  • Ph.D., Cancer Biology, Stanford University, Stanford, CA 1996

Experience: 

  • Research Assistant Professor, Department of Biology, Rensselaer Polytechnic Institute, Troy, NY

Areas of research:

  • Nanomotors and Microtubule Networks
  • Microtubule organizing centers (MTOCs)
  • Cell Cycle mechanisms /Mitosis
  • Cancer Biology
  • Pluripotent stem cells (hESC, iPS cells) and nuclear reprogramming 
  • Stem cell applications to 3D Tissue Engineering
  • bioMEMS, Biosensors

Research Description: Cellular Machines and Multi-cellular Design Principles

Research in Dr. Paluh's lab applies tools of nanotechnology to understand self-assembly mechanisms in biology related to cellular machines and complex multi-cellular and multi-cell type tissue and organ design principles. We focus on cellular machines of the eukaryotic microtubule cytoskeleton system, particularly the mitotic spindle and including kinesin nanomotors, microtubules, and microtubule organizing center (MTOC) function of centrosomes and spindle pole bodies. As well we apply stem cell biology to understand assembly of complex 3D tissues to inform on in vitro tissue engineering applications for normal development as well as disease mechanisms and including use of reprogramming strategies for biomarker identification in cancer biology. Research in Dr. Paluh's lab has advanced the field of mitosis through discovery of novel mechanisms in spindle assembly. This includes spindle pole based asymmetry pathways as well as identification of novel kinesin-like protein (Klp) interactions with the microtubule organizing center (MTOC) γ-tubulin ring complex (γ-TuRC) to modify its structure and function. The macromolecular γ-TuRC is the site of microtubule nucleation and polar attachment and therefore of great interest in establishment of internal cellular microtubule-incorporating architectures for genomic stability and specialized cell functions such as neural networks. In stem cell research we have derived new xenofree human pluripotent stem cell lines from African American, Hispanic Latino and Asian ethnicity as a clinical and research resource with analysis of whole genome transcriptome, microRNA, and histone epigenetic profiling. We apply custom photolithography-templating to design microarrays, microsieves and patterning devices for high throughput embryoid body (EB) formation and differentiation analysis as well as applications in cancer research. Stem cell studies are supported in part by NYSTEM. Collaborative projects are underway in breast and pancreatic cancers and in establishing 3D neural-glia co-cultures for technology integration. Our work applies nanotechnology, human and yeast genetic strategies, stem cell biology, timelapse 3D microscopy, biochemistry, molecular biology and bioinformatic modeling and structural and systemic approaches.

Cellular Machines: Function & NanoEngineering of the Mitotic Spindle Apparatus
  • Cellular Motors and Microtubules in Nanofabrication. Biomimicry applications with mitotic spindle components provide an ideal model of self-assembling and regulating machine principles. Compared to lithography-templated designs used by man, cellular systems can self-assemble, error correct, adapt, and re-organize—flexible principles that would be invaluable for nano-microscale manufacturing. In addition, how communication networks operate at the nanoscale and traverse to micro and macroscale effects is not well understood and would benefit by biomimetic system studies. We are interfacing nanomotor kinesin-like proteins and isolated MTOCs along with other microtubule-regulators with man-made materials to model nanoscale communication networks and develop hybrid programmable systems.
  • Kinesin-like proteins (Klps) and microtubules in transport mechanisms. Klps are master regulators of the microtubule cytoskeleton and coordinated to perform diverse roles in transport, signaling and cytoskeleton remodeling. At least 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 γ-TuRC MTOC. The Microtubule Organizing Centers (MTOCs) is a site of microtubule growth, organization and dynamics and a signaling hub for cell cycle progression. The MTOC macromolecular complexes participate in a variety of diverse structures central to specialized cellular functions. Unique reagents developed in the Paluh lab are being used to define at the molecular level conserved structural and functional parameters of MTOCs, focusing on regulation of the γ-TuRC by temporally associated proteins for applications from cancer therapies to nanofabrication.
  • Asymmetric processes & checkpoints. Cells avoid fatal system failures that can lead to cell, tissue or organism death by monitoring cell cycle progression to allow for error correction. Checkpoints overlay underlying cellular mechanisms to provide a fail-safe mechanism. In multi-cellular eukaryotes checkpoints may ‘time out’ 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 understanding these mechanisms will aid in design of synthetic 4D spatiotemporal cellular niches.
Multicellular Design Principles in Development and Disease
  • Development of an optimized synthetic niche. 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. Our knowledge of the ideal stem cell microenvironment in culture though advancing remains rudimentary and currently inadequate for stem cell expansion, directed differentiation, high throughput screening, and biomedical therapies. The Paluh lab is applying nanotechnology tools towards developing functionalized hydrogel scaffolds and cell patterning approaches to stem cell differentiation and complex multi-cell type 3D tissue engineering.
  • Human embryonic stem cells. hESCs offer unlimited potential for human therapies. Limited ethnic diversity exists in current lines that is being addressed in part by a ~$1M NYSTEM award for derivation, teratoma and in vitro differentiation analysis and whole genome characterization of transcriptome, microRNAs, and histone epigenetic modifications. This work is in collaboration with renowned stem cell expert, Dr. Jose Cibelli, Michigan State University, and takes advantage of new nanotechnology-based strategies. The lines will be banked for scientific community, biomedical and industry use and follow NYSTEM ISSCR and National Academy of Science guidelines.
  • Nuclear reprogramming. The generation of induced pluripotent stem cells (iPSCs) provides an opportunity to understand key genetic and epigenetic requirements in normal and diseased tissues. The Paluh lab is interested in key cell cycle and cytoskeleton signaling pathways regulating iPSC populations during lineage reprogramming and disease development.

Selected Professional Contributions

  • University at Albany Institutional Review Board (IRB), Co-Chair
  • Stem Cell Research Oversight (SCRO), member/former Chair
  • Board of Directors, Girls Incorporated Non-Profit
  • Project Lead the Way Panel ‘Nano’izing K-12’
  • IEEE P1906.1 NanoCom Working Group “Recommended Practice for Nanoscale and Molecular Communication Framework”
  • Faculty of 1000 Associate Faculty Reviewer, Cell Biology, Cytoskeleton
  • Editorial Board, Advances in Stem Cell Discovery
  • Editorial Board, IEEE Transactions on Molecular, Biological, and Multi-scale Communications (T-MBMC)
  • NSF MRI Panel, Division of Biological Infrastructure
  • Mentor for 2013 Goldwater Scholar undergraduate awardee

Interviews, Invited Reviews, Book Chapters

  1. Paula Monaco (Sept 10, 2013) Under the Microscope, Capital Magazine, Albany, NY
  2. Paul Grondahl (Mar 25, 2013) Ready to Unlock Stem Cell Mysteries, Times Union, Albany, NY
  3. Riehlman T., Olmsted, Z. and Paluh J.L. (2012) Nanomachines: Molecular Motors, Chapter in Nanotechnology Handbook, CRC Press/Taylor and Francis Group. Published 2012.
  4. 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.
  5. Paluh, J.L. (2011) Towards nanorobotics, nanonetworks, and self-assembling and regulating machines. Nanotechnology Now. http://www.nanotech-now.com/columns/?article=507

Recent Publications:

  1. M.L. Tomov, Z.T. Olmsted, and J.L. Paluh (2014) Lithography templated hESC embryoid bodies optimized for rapid uniform 3D formation, size, structural integrity and differentiation. Submitted to Biomaterials.
  2. Z.T. Olmsted, A. Colliver, T.D. Riehlman, A. Winnie and J.L. Paluh (2013) Regulated γ-TuRC microtubule nucleation by opposing actions of Kinesin-5 and Kinesin-14. Submitted to J. Cell Biology
  3. T.D. Riehlman, Z.T. Olmsted, C.N. Branca, A. Winnie, L. Seo, L.O. Cruz, and J.L. Paluh (2013) Functional replacement of fission yeast γ-tubulin small complex proteins Alp4 and Alp6 by human GCP2 and GCP3. J Cell Sci. epub ahead of print.
    http://www.ncbi.nlm.nih.gov/pubmed/23886939
  4. Z.T. Olmsted, T.D. Riehlman, C.N. Branca, A. Colliver, A. Winnie and J.L. Paluh (2013) Kinesin-14 Pkl1 targets γ-tubulin for release from the g-tubulin ring complex (γ-TuRC). Cell Cycle 12(5): 842-848.
    http://www.ncbi.nlm.nih.gov/pubmed/23388459
  5. Gasimli, L., Stansfield, H.E., Nairn, A.V., Liu, H., Paluh, J.L., Yang, B., Dordick J.S., Moreman, K.W., and R. J. Linhardt (2013) Structural remodeling of proteoglycans on retinoic acid-induced differentiation of NCCIT cells. Glyconjugate J. 30:497-510. http://www.ncbi.nlm.nih.gov/pubmed/23053635
  6. 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
  7. 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.
  8. 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.
  9. 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.
  10. Paluh, J.L. (2008) Sentinels of DNA integrity in stem cells. Cell Cycle 7(18): 2779-2780.
  11. Paluh, J.L. (2008) Kinesin-14 leaps to pole position in bipolar spindle assembly. Chinese Journal of Cancer, 27(9): 1-5.
  12. 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.
  13. 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.
  14. 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.
  15. 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.