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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:

  1. Nina Notman (Dec 2014) Let Molecules Do the Talking, Chemistry World. http://www.rsc.org/chemistryworld/2014/12/let-molecules-do-talking
  2. Paula Monaco (Sept 2013) Under the Microscope, Capital Magazine, Albany, NY
  3. Paul Grondahl (Mar 2013) Innovators Series: Ready to Unlock Stem Cell Mysteries, Times Union, Albany, NY

    Recent Publications and Book Chapters:

    1. M.L. Tomov, Z.T. Olmsted, and J.L. Paluh (2014) Size-dependent complexity in the human embryoid body cystic core contributes to differentiation non-uniformity. Stem Cells and Development, submitted.
    2. S.F. Bush, J.L. Paluh, G. Piro, V. Rao, V. Prasad, and A. Eckford (2014) Defining Communication at the Bottom. IEEE Journal on Selected Areas of Communication (JSAC): Molecular, Biological and Multi-Scale Communications submitted.
    3. Z.T. Olmsted, A. Colliver, and J.L. Paluh (2014) The Kinesin-tubulin complex: Mechanistic considerations in structure and function. Cell Health and Cytoskeleton, in press.
    4. Z.T. Olmsted, A. Colliver, T.D. Riehlman, and J.L. Paluh (2014) Kinesin-14 and kinesin-5 antagonistically regulate microtubule nucleation γ-TuRC in yeast and human cells. Nature Communications 5:5339. PMID:25348260 
    5. 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. 126: 4406-4413. PMID: 23886939
    6. 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 γ-tubulin ring complex (γ-TuRC). Cell Cycle 12(5): 842-848. PMID: 23388459
    7. L. Gasimli, H.E. Stansfield, A.V. Nairn, H. Liu, J.L. Paluh, B. Yang, J.S. Dordick, K.W. Moreman, and R. J. Linhardt (2013) Structural remodeling of proteoglycans on retinoic acid-induced differentiation of NCCIT cells. Glyconjugate J. 30: 497-510. PMID: 23053635. 
    8. T.D. Riehlman, Z.T. Olmsted, and J.L. Paluh (2012) Nanomachines: Molecular Motors, Chapter in Nanotechnology Handbook, CRC Press/Taylor and Francis Group. ISBN:9781439838693
    9. J.L. Paluh, J.L. (2011) Towards nanorobotics, nanonetworks, and self-assembling and regulating machines. Nanotechnology Now. http://www.nanotech-now.com/columns/?article=507
    10. J.L. Paluh, G. Dai, and D.B. Chrisey (2011) In search of the Holy Grail: Engineering the stem cell niche. European Pharmaceutical Review. 16(2): 28-33
    11. B. Riggs, J.L. Paluh, G. Plopper, and D.B. Chrissy (2011) Impedence Spectroscopy for Characterization of Biological Function, Chapter 12 in NanoCellBiology: Multimodal Imaging In Biology and Medicine, Pan Sanford Publishing Pte. Ltd. ISBN: 9789814411790 
    12. D.R. Simeonov, K. Kenny, A. Moyer, L. Seo, J. Allen, and J.L. Paluh (2009) Distinct Kinesin-14 mitotic mechanisms in spindle bipolarity. Cell Cycle 8(21): 3571-3583. PMID:19838064 * featured in News and Views, 8(21): 3452-3454. PMID:19855184
    13. J.L. Paluh (2008) Sentinels of DNA integrity in stem cells. Cell Cycle 7(18): 2779-2780. DOI: 10.4161/cc.7.18.6890
    14. J.L. Paluh (2008) Kinesin-14 leaps to pole position in bipolar spindle assembly. Chinese Journal of Cancer, 27(9): 1-5. PMID:18799042
    15. A.S. Rodriguez, J. Batac, A.N. Killilea, J. Filopei, D.R. Simeonov, I. Lin, and J.L. Paluh (2008) Protein complexes at the microtubule organizing center regulate bipolar spindle assembly. Cell Cycle. 7(9): 1246-1253. PMID:18418055
    16. C.L. Mayer, J. Filopei, J. Batac, L. Alford, 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. PMID:16855399
    17. J.L. Paluh, A.N. Killilea, W. Detrich III, 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. PMID:14657251
    18. J.L. Paluh, E. Nogales, B.R. Oakley, K. McDonald, A.L. Pidoux, 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. PMID:10749926

    Patents:

    • J.L. Paluh and Z.T. Olmsted. MTOC Inactivating Peptides. Provisional Patent Application Numbers: 61/939.461 and 62/062,465.

    International Presentations:

    • Workshop 14w5170: Biological and Bio-Inspired Information Theory. Banff International Research Station for Mathematical Innovation and Discovery (BIRS), Canada, Oct 2014.
    • EMBO Conference on Centrosomes and Spindle Pole Bodies, Heidelberg, Germany, Sept 2008
    • EMBO Workshop on Centrosomes and Spindle Pole Bodies, Heidelberg, Germany, Sept 2005
    • Paterson Institute for Cancer Research, Manchester, United Kingdom, July 2004
    • European Pombe Meeting, Lausanne, Switzerland, June 2003
    • EMBO/EMBL Conference on Centrosomes and Spindle Pole Bodies, Heidelberg, Germany, Sept 2002
    • Second International Fission Yeast Meeting, Kyoto, March 2002
    • EMBO Workshop on Centromeres, Kinetochores and Spindle Function, Heidelberg, Germany, October 2000
    • First International Fission Yeast Meeting, Edinburgh, Scotland, September 1999

    National Presentations:

    • Western New York Stem Cell Conference (WNYSTEM), SUNY Buffalo, NY June 2015.
    • Society of Biological Engineers and International Society of Stem Cell Research (SBE-ISSCR), 4th International Conference on Stem Cell Engineering. Coronado, CA, Febr 2014
    • Capital Region Cancer Research Group, Albany, NY, June 2014
    • Spinal Cord Society Capital District Chapter, 29th Annual Research Benefit, April 2013
    • NYSTEM Collaboration and Renewal Annual Conference. New York, NY May, 2013
    • Capital Region Cancer Research New Frontiers Symposium, Albany, NY Nov 2012.
    • North American Regional Pombe Meeting, University of California, Los Angeles, CA, June 2008
    • American Cancer Society, Relay for Life, Troy, NY, May 2008
    • Sanford/Burnham Medical Research Institute, Stem Cells and Regenerative Biology, La Jolla, CA, July 2006
    • Buck Institute for Research on Aging, Novato, CA, July 2006
    • Second East Coast Regional Fission Yeast Meeting, Miami, FL, November 2005
    • Department of Cell Biology, Emory University School of Medicine, Atlanta, GA. May 2005
    • Third International Fission Yeast Meeting, San Diego, CA, August 2004
    • Annual Meeting American Society of Cell Biology, Minisymposium: Spindles and Spindle Poles, Washington D.C., Dec 1999

    Selected Educational Presentations:

    • Project Lead the Way Innovation Summit, Panelist ‘Nano’izing K-12’ Washington, D.C. Oct 2010.
    • NEATEC, Northeastern Advanced Technological Innovation Center, ‘Preparing the Technology Workforce’. Hudson Valley Community College, Rensselaer, Nov 2011.
    • ESATCYB, Empire State Association of Two-Year College Biologists, Annual Conference, ‘Nanotechnology in Research and Education’, Fulton-Montgomery Community College, Johnstown, NY, April 2012.
    • SUNYIT Nanotechnology Forum, “Nanotech 101” Utica, NY, May 2012.
    • The OASIS Organization for healthy ageing, ‘Nanotechnology and Stem Cells’, Albany, NY, Nov 2011.